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CompletedNCT04493931Updated Mar 4, 2022Results posted

Drug-drug Interaction Study of Gepotidacin

A Phase 1 interventional study of Gepotidacin and Cimetidine in Infections, Bacterial, sponsored by GlaxoSmithKline. Completed at 1 site in United States. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-03-04.

Sponsored by GlaxoSmithKline · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
64
Allocation
Randomized
Ages
18 Years to 50 Years
Sex
All
01

Study summary

This study is a drug-drug interaction (DDI), pharmacokinetics (PK), safety and tolerability study in adult healthy participants, including Japanese cohort. This study is designed to assess co-administration of probe substrates with gepotidacin in study cohorts 1 to 3 and establishing PK and safety in Japanese participants in cohort 4. Food effect will also be evaluated in cohort 4.

02

Conditions studied

  • Infections, Bacterial

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Keywords

  • Gepotidacin
  • Drug Interaction
  • Pharmacokinetic
  • Safety
  • Bacterial Infection
  • Japanese Healthy Adults
03

In context

Bacterial Infections

658 studies on the registry are indexed under Bacterial Infections; 100 are open to participants now.

This study's enrollment of 64 is below the median of 84 across 405 interventional studies indexed under Bacterial Infections.

Browse Bacterial Infections studies →

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 50 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Participant must be greater than or equal to (>=) 18 to less than or equal to (=\<) 50 years of age inclusive, at the time of signing the informed consent.
  • Participants who are healthy as determined by the investigator or medically qualified designee based on medical evaluation including medical history, physical examination, clinical laboratory tests, vital sign measurements, and 12-lead ECG results. A participant with clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the investigator feels and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
  • Additional inclusion criteria for Japanese participants (Cohort 4): The participant is a non-naturalized Japanese citizen and holds a Japanese passport (current or expired).

The participant has/had 2 Japanese parents and 4 Japanese grandparents who are/were all non-naturalized Japanese citizens, as confirmed by interview.

The participant has been living outside of Japan for up to 10 years as confirmed by interview.

  • Participants have a body weight >=40 kilograms (kg) and body mass index within the range 18.5 to 32.0 kilograms per square meter (kg/m\^2) (inclusive).

  • Male and/or female: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

    1. Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies: Is a woman of non-childbearing potential or Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of \<1 percent (%), for at least 30 days prior to dosing until completion of the follow-up Visit. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.

A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) before the first dose of study intervention and for women not on effective contraception at least 14 days prior to baseline visit.

The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.

  • Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.

Exclusion criteria

Exclusion Criteria:

  • Clinically significant abnormality in the past medical history or at the screening physical examination that in the investigator's opinion may place the participant at risk or interfere with the outcome variables of the study. This includes, but is not limited to, history or current cardiac, hepatic, renal, neurologic, gastro-intestinal (GI), respiratory, hematologic, or immunologic disease.
  • Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study intervention, or any other condition that may place the participant at risk, in the opinion of the investigator.
  • Female participant has a positive pregnancy test result or is lactating at Screening or upon admission to the clinic.
  • Positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Note: Testing will be performed according to site procedures.
  • Within 2 months before Screening, either a confirmed history of Clostridium difficile (C. difficile) diarrhea infection or a past positive of C. difficile toxin test.
  • Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
  • History of drug and/or alcohol abuse within 6 months before Screening, as determined by the investigator, or has a positive drug screen at Screening or upon admission to the clinic.
  • History of sensitivity/hypersensitivity to any of the study drugs, components thereof, or a history of drug or other allergy that, in the opinion of the Investigator or GlaxoSmithKline (GSK) Medical Monitor contraindicates their participation.
  • Cohort 2 Only: Participant is a contact lens wearer who is unable or unwilling to wear glasses for the duration of the study and for 5 half-lives after the last dose of rifampicin.
  • Use of any systemic antibiotic within 30 days of screening.
  • Participants must abstain from taking prescription or non-prescription drugs (except for hormonal contraceptives and/or acetaminophen at doses of \<=2 grams/day), vitamins, and dietary or herbal supplements, within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to study intervention until completion of the follow-up Visit, unless, in the opinion of the investigator and Sponsor, the medication will not interfere with the study. Any exceptions will be discussed with the Sponsor or Medical Monitor on a case-by-case basis and the reasons will be documented.
  • Previous exposure to gepotidacin.
  • Participant has participated in a clinical trial and has received an investigational product (IP) prior to gepotidacin administration within 30 days, 5 half-lives, or twice the duration of the biological effect of IP (whichever is longer).
  • Past participation in this clinical study.
  • Baseline corrected QT interval using the Fridericia formula (QTcF) of >450 milliseconds (msec) at Screening or Check-in.
  • Presence of hepatitis B surface antigen or positive hepatitis C antibody test result at Screening or within 3 months prior to starting study intervention.
  • Alanine aminotransferase (ALT) >1.5 times upper limit of normal (ULN) at Screening or Check-in.
  • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%) at Screening or Check-in.
  • History of any kidney disease or current or chronic history of mild impaired renal function as indicated by an estimated creatinine clearance \<=90 milliliters per minute (mL/min).
  • A positive test for human immunodeficiency virus (HIV) antibody.
  • History of regular alcohol consumption within 6 months of Screening defined as an average weekly intake of >21 units (or an average daily intake of >3 units) for males or an average weekly intake of >14 units (or an average daily intake >2 units) for females. One unit is equivalent to 270 mL of full strength beer, 470 mL of light beer, 30 mL of spirits, or 100 mL of wine.
  • Cohort 3 Only: Digoxin-related exclusions include the following at Screening:

Serum potassium >5.5 milliequivalent per liter (mEq/L) or \< 3.6 mEq/L Serum magnesium \<1.6 milligrams per deciliter (mg/dL) Serum calcium (total) \<8.5 mg/dL History of hypersensitivity to digoxin or other digitalis glycosides Any clinically relevant abnormality on 12-lead ECG at Screening or Check-in.

  • Participant has donated blood in excess of 500 mL within 12 weeks prior to dosing or participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56-day period.
  • Participant is unable to comply with all study procedures, in the opinion of the investigator.
  • Participant should not participate in the study, in the opinion of the investigator or Sponsor.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Investigator)
Enrollment
64 participants (actual)

Study arms

  • Experimental
    Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg

    This is a fixed sequence (Sequence AB) cohort. Participants will receive gepotidacin 1500 milligrams (mg) single dose (SD) on Day 1 of Period 1 (Treatment A); and Cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 and gepotidacin 1500 mg single dose (Treatment B). Gepotidacin will be administered 1 hour after the first dose of cimetidine on Day 2 of Period 2. There will be a washout of at least 3 days between Treatment A and Treatment B, and a follow-up visit 5 to 7 days after the last dose of cimetidine.

    Drug: Gepotidacin · Drug: Cimetidine

  • Experimental
    Cohort 2: Gepotidacin 1500 mg + Rifampicin 600 mg

    This is a fixed sequence (Sequence CDE) cohort. Participants will receive gepotidacin 1500 mg single dose on Day 1 of Period 1 (Treatment C), rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7 of Period 2, to elicit maximal enzyme induction) (Treatment D); and gepotidacin 1500 mg single dose administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 (Treatment E). There will be a washout of at least 3 days between Treatment C and Treatment D, and a follow-up visit 7 to 10 days after the last dose of rifampicin.

    Drug: Gepotidacin · Drug: Rifampicin

  • Experimental
    Cohort 3: Digoxin 0.5mg+Midazolam 2mg then Gepotidacin 3000mg

    Participants will receive digoxin 0.5 mg and midazolam 2 mg (Treatment F) in Period 1 on Day 1 then gepotidacin two 3000 mg doses (given 12 hours apart) co-administered with digoxin 0.5 mg and midazolam 2 mg in Period 2 on Day 1, with the 2 probe drugs administered with the second daily dose of gepotidacin only (Treatment G). There will be a washout of at least 10 days between treatments. In Sequence 2, these regimens are reversed. A follow-up visit will occur 7 to 10 days after the last dose of study intervention in Period 2.

    Drug: Gepotidacin · Drug: Midazolam · Drug: Digoxin

  • Experimental
    Cohort 3: Gepotidacin 3000mg then Digoxin 0.5mg+Midazolam 2mg

    Participants will receive gepotidacin two 3000 mg doses (given 12 hours apart) co-administered with digoxin 0.5 mg and midazolam 2 mg in Period 1 on Day 1, with the 2 probe drugs administered with the second daily dose of gepotidacin only (Treatment G) followed by digoxin 0.5 mg and midazolam 2 mg (Treatment F) in Period 2 on Day 1. A follow-up visit will occur 7 to 10 days after the last dose of study intervention in Period 2.

    Drug: Gepotidacin · Drug: Midazolam · Drug: Digoxin

  • Experimental
    Cohort 4: Gepotidacin 1500 mg fed then fasted then 3000 mg fed

    Cohort 4 will include Japanese participants. Participants will receive a single dose of gepotidacin 1500 mg under fed conditions in Period 1 (Treatment H), then a single dose of gepotidacin 1500 mg under fasted conditions in Period 2 (Treatment I), followed by two doses of gepotidacin up to 3000 mg (given 12 hours apart) under fed conditions in Period 3 (Treatment J). There will be a washout of at least 3 days between each treatment, and a follow-up visit 5 to 7 days after the last dose of gepotidacin.

    Drug: Gepotidacin

  • Experimental
    Cohort 4: Gepotidacin 1500 mg fasted then fed then 3000 mg fed

    Cohort 4 will include Japanese participants. Participants will receive a single dose of gepotidacin 1500 mg under fasted conditions in Period 1 (Treatment I), then a single dose of gepotidacin 1500 mg under fed conditions in Period 2 (Treatment H), followed by two doses of gepotidacin up to 3000 mg (given 12 hours apart) under fed conditions in Period 3 (Treatment J). There will be a washout of at least 3 days between each treatment, and a follow-up visit 5 to 7 days after the last dose of gepotidacin.

    Drug: Gepotidacin

  • Placebo comparator
    Cohort 4: Placebo fed then fasted then fed

    Cohort 4 will include Japanese participants. Participants will receive a single dose of placebo under fed conditions in Period 1, then a single dose of placebo under fasted conditions in Period 2, followed by two doses of placebo (given 12 hours apart) under fed conditions in Period 3. There will be a washout of at least 3 days between each period, and a follow-up visit 5 to 7 days after the last dose of placebo.

    Other: Placebo matching to gepotidacin

Interventions

  • DrugGepotidacin

    Gepotidacin tablets will be available as unit dose strength 750 mg and will be administered orally.

    Also known as: GSK2140944

  • DrugCimetidine

    Cimetidine tablets will be available as unit dose strength 400 mg and will be administered orally.

  • DrugRifampicin

    Rifampicin Capsules will be available as unit dose strength 300 mg and will be administered orally.

  • DrugMidazolam

    Midazolam oral syrup 2 milligrams per milliliter (mg/mL) will be available to be administered orally.

  • DrugDigoxin

    Digoxin tablets will be available as unit dose strength 0.25 mg and will be administered orally.

  • OtherPlacebo matching to gepotidacin

    Placebo matching to gepotidacin tablets will be administered orally.

06

What researchers measure

Primary outcomes

  1. Cohort 1: Maximum Observed Concentration (Cmax) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric least square (LS) mean and 90 percent (%) confidence interval (CI) of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  2. Cohort 1: Time to Reach Maximum Observed Concentration (Tmax) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  3. Cohort 1: Terminal Phase Half-life (t1/2) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  4. Cohort 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  5. Cohort 1: AUC From Time 0 (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  6. Cohort 2: Cmax of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  7. Cohort 2: Lag Time Before Observation of Drug Concentrations (Tlag) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  8. Cohort 2: Tmax of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  9. Cohort 2: AUC(0-t) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  10. Cohort 2: AUC(0-infinity) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  11. Cohort 3: Cmax of Digoxin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2

  12. Cohort 3: Tlag of Digoxin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2

  13. Cohort 3: Tmax of Digoxin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2

  14. Cohort 3: AUC(0-t) of Digoxin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2

  15. Cohort 3: AUC(0-infinity) of Digoxin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2

  16. Cohort 3: Cmax of Midazolam in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  17. Cohort 3: Tlag of Midazolam in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  18. Cohort 3: Tmax of Midazolam in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  19. Cohort 3: AUC(0-t) of Midazolam in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  20. Cohort 3: AUC(0-infinity) of Midazolam in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  21. Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  22. Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  23. Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 24 Hours Post-dose (AUC[0-24]) of Gepotidacin Following Single Dose of 1500 mg in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours post-dose in each Treatment Periods 1 and 2

  24. Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 48 Hours Post-dose (AUC[0-48]) of Gepotidacin Following Single Dose of 1500 mg in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  25. Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  26. Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  27. Cohort 4: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  28. Cohort 4: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  29. Cohort 4: AUC From Time 0 (Predose) to Time Tau (AUC[0-tau]) of Gepotidacin in Plasma After the First Dose of 3000 Mg-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  30. Cohort 4: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  31. Cohort 4: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  32. Cohort 4: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Evening Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  33. Cohort 4: Accumulation Ratio Based on Cmax (RoCmax) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  34. Cohort 4: Accumulation Ratio Based on AUC(0-tau) (RoAUC) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) after the second dose, where 0 is the timepoint prior to second dose, divided by AUC(0-tau) after the first dose, where 0 is the predose timepoint prior to the first dose.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  35. Cohort 4: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24 Hours post-dose in Treatment Period 3

  36. Cohort 4: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48 Hours post-dose in Treatment Period 3

  37. Cohort 4: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  38. Cohort 4: Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE)

    An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.

    Time frame: Up to 22 days

  39. Cohort 4: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

    Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, Erythrocyte Mean Corpuscular Hemoglobin (MCH), Erythrocyte Mean Corpuscular Volume (MCV), Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose laboratory (lab) value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 (%). High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Time frame: Up to 22 days

  40. Cohort 4: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

    Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase (Alk Phos), Aspartate Aminotransferase (AST), Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, Blood Urea Nitrogen (BUN). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Time frame: Up to 22 days

  41. Cohort 4: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline

    Urine samples were collected at indicated time points for the analysis of urinalysis parameters including potential of hydrogen (pH) of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Time frame: Up to 22 days

  42. Cohort 4: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline

    Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Time frame: Up to 22 days

  43. Cohort 4: Number of Participants With Any Increase in Maximum Post-Baseline Electrocardiogram (ECG) Parameter Corrected QT (QTc) Interval

    A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of \>450 milliseconds in corrected QT interval using the Bazett formula (QTcB) Interval and corrected QT interval using the Fridericia formula (QTcF) Interval has been reported.

    Time frame: Up to 22 days

  44. Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  45. Cohort 4: Tlag of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  46. Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  47. Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  48. Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

Secondary outcomes

  1. Cohort 1: AUC (0-24) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in each Treatment Periods 1 and 2

  2. Cohort 1: AUC(0-48) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  3. Cohort 1: Tlag of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  4. Cohort 1: Apparent Volume of Distribution (Vz/F) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  5. Cohort 1: Apparent Oral Clearance (CL/F) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2

  6. Cohort 1: Total Unchanged Drug (Ae Total) of Gepotidacin in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2

  7. Cohort 1: AUC(0-24) of Gepotidacin in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours Post-dose in each Treatment periods 1 and 2

  8. Cohort 1: AUC(0-48) of Gepotidacin in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2

  9. Cohort 1: Renal Clearance (CLr) of Gepotidacin

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2

  10. Cohort 1: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.

    Time frame: 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment periods 1 and 2

  11. Cohort 1: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 percent (%).

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2

  12. Cohort 1: Number of Participants With SAE and Non-SAE

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.

    Time frame: Up to 17 days

  13. Cohort 1: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

    Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 %. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Time frame: Up to 17 days

  14. Cohort 1: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

    Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Time frame: Up to 17 days

  15. Cohort 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline

    Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Time frame: Up to 17 days

  16. Cohort 1: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline

    Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Time frame: Up to 17 days

  17. Cohort 1: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval

    A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of \>450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported.

    Time frame: Up to 17 days

  18. Cohort 2: AUC(0-24) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours post-dose in each Treatment Periods 1 and 2

  19. Cohort 2: AUC(0-48) of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  20. Cohort 2: T1/2 of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  21. Cohort 2: Vz/F of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  22. Cohort 2: CL/F of Gepotidacin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  23. Cohort 2: Ae Total of Gepotidacin in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  24. Cohort 2: AUC(0-24) of Gepotidacin in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours post-dose in each Treatment Periods 1 and 2

  25. Cohort 2: AUC(0-48) of Gepotidacin in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  26. Cohort 2: CLr of Gepotidacin

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  27. Cohort 2: Ae(t1-t2) of Gepotidacin

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.

    Time frame: 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  28. Cohort 2: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  29. Cohort 2: Number of Participants With SAE and Non-SAE

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.

    Time frame: Up to 26 days

  30. Cohort 2: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

    Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Time frame: Up to 26 days

  31. Cohort 2: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

    Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Time frame: Up to 26 days

  32. Cohort 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline

    Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Time frame: Up to 26 days

  33. Cohort 2: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline

    Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Time frame: Up to 26 days

  34. Cohort 2: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval

    A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of \>450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported.

    Time frame: Up to 26 days

  35. Cohort 3: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  36. Cohort 3: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  37. Cohort 3: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  38. Cohort 3: AUC(0-tau) of Gepotidacin in Plasma First Dose of 3000 mg (First Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  39. Cohort 3: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  40. Cohort 3: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  41. Cohort 3: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  42. Cohort 3: RoCmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  43. Cohort 3: RoAUC of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) after the second dose, where 0 is the timepoint prior to second dose, divided by AUC(0-tau) after the first dose, where 0 is the predose timepoint prior to the first dose.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  44. Cohort 3: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24 Hours post-dose in each Treatment Periods 1 and 2

  45. Cohort 3: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48 Hours post-dose in each Treatment Periods 1 and 2

  46. Cohort 3: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  47. Cohort 3: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  48. Cohort 3: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  49. Cohort 3: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose+ Second Dose)

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2

  50. Cohort 3: Minimum Observed Concentration (Cmin) of Digoxin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2

  51. Cohort 3: T1/2 of Digoxin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2

  52. Cohort 3: Vz/F of Digoxin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2

  53. Cohort 3: CL/F of Digoxin in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2

  54. Cohort 3: Cmin of Midazolam in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  55. Cohort 3: T1/2 of Midazolam in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  56. Cohort 3: Vz/F of Midazolam in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  57. Cohort 3: CL/F of Midazolam in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  58. Cohort 3: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose )

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2

  59. Cohort 3: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose)

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2

  60. Cohort 3: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2

  61. Cohort 3: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours post-dose in each Treatment Periods 1 and 2

  62. Cohort 3: AUC (0-48) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  63. Cohort 3: Percentage of the Given Dose of Drug Excreted in Urine (fe%) Following Two 3000 mg Doses of Gepotidacin (First Dose + Second Dose )

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2

  64. Cohort 3: CLr of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose)

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2

  65. Cohort 3: Number of Participants With SAE and Non-SAE

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.

    Time frame: Up to 30 days

  66. Cohort 3: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

    Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Time frame: Up to 30 days

  67. Cohort 3: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

    Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Time frame: Up to 30 days

  68. Cohort 3: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline

    Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Time frame: Up to 30 days

  69. Cohort 3: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline

    Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

    Time frame: Up to 30 days

  70. Cohort 3: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval

    A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of \>450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported.

    Time frame: Up to 30 days

  71. Cohort 4: T1/2 of Gepotidacin Following Single Dose of 1500 mg in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  72. Cohort 4: Vz/F of Gepotidacin Following Single Dose of 1500 mg in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  73. Cohort 4: CL/F of Gepotidacin Following Single Dose of 1500 mg in Plasma

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2

  74. Cohort 4: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  75. Cohort 4: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  76. Cohort 4: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  77. Cohort 4: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose )-Fed State

    Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3

  78. Cohort 4: Ae Total of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  79. Cohort 4: Ae(t1-t2) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  80. Cohort 4: AUC(0-24) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours post-dose in each Treatment Periods 1 and 2

  81. Cohort 4: AUC(0-48) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  82. Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) for Gepotidacin 1500 mg Under Fed Condition

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100%.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  83. Cohort 4: CLr of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

  84. Cohort 4: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3

  85. Cohort 4: Ae(t1-t2) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3

  86. Cohort 4: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3

  87. Cohort 4: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours post-dose in Treatment Period 3

  88. Cohort 4: AUC(0-48) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours post-dose in Treatment Period 3

  89. Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin Following Two 3000 mg Doses-Fed State

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3

  90. Cohort 4: CLr of Gepotidacin Following Two 3000 mg Dose-Fed State

    Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3

Other outcomes

  1. Cohort 4: AUC(0-tau) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine

    Urine samples were collected at indicated time points. AUC(0-tau) can be calculated only for multiple doses and not for single dose as tau refers to the dosing interval. Hence, AUC(0-tau) could not be calculated for Gepotidacin 1500 mg single dose as mentioned in Reporting and Analysis Plan. The results for this outcome measure will never be posted.

    Time frame: Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2

07

Results

Posted Mar 4, 2022

Participant flow

This study was conducted at a single center in the United States and designed to assess co-administration of probe substrates with gepotidacin in study Cohorts 1 to 3 and establishing pharmacokinetics and safety in a Japanese cohort in Cohort 4.

Cohort1:Treatment Period 1(Up to 3 Days)
Participant flow — Cohort1:Treatment Period 1(Up to 3 Days)
MilestoneCohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed
Started14000000
Completed13000000
Not completed1000000
Withdrew: Adverse event1000000
Cohort 1:Washout Period 1 (Up to 3 Days)
Participant flow — Cohort 1:Washout Period 1 (Up to 3 Days)
MilestoneCohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed
Started13000000
Completed13000000
Not completed0000000
Cohort1:Treatment Period 2(Up to 4 Days)
Participant flow — Cohort1:Treatment Period 2(Up to 4 Days)
MilestoneCohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed
Started13000000
Completed13000000
Not completed0000000
Cohort 1: Follow-up (Up to 7 Days)
Participant flow — Cohort 1: Follow-up (Up to 7 Days)
MilestoneCohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed
Started13000000
Completed13000000
Not completed0000000
Cohort2:Treatment Period 1(Up to 3 Days)
Participant flow — Cohort2:Treatment Period 1(Up to 3 Days)
MilestoneCohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed
Started01700000
Completed01700000
Not completed0000000
Cohort 2:Washout Period 1(Up to 3 Days)
Participant flow — Cohort 2:Washout Period 1(Up to 3 Days)
MilestoneCohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed
Started01700000
Completed01700000
Not completed0000000
Cohort2:Treatment Period2(Up to 10 Days)
Participant flow — Cohort2:Treatment Period2(Up to 10 Days)
MilestoneCohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed
Started01700000
Completed01400000
Not completed0300000
Withdrew: Physician decision0200000
Withdrew: Withdrawal by subject0100000
Cohort 2: Follow-up (Up to 10 Days)
Participant flow — Cohort 2: Follow-up (Up to 10 Days)
MilestoneCohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed
Started01400000
Completed01400000
Not completed0000000
Cohort3:Treatment Period 1(Up to 5 Days)
Participant flow — Cohort3:Treatment Period 1(Up to 5 Days)
MilestoneCohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed
Started00109000
Completed0099000
Not completed0010000
Withdrew: Protocol violation0010000
Cohort3:Washout Period 1(Up to 10 Days)
Participant flow — Cohort3:Washout Period 1(Up to 10 Days)
MilestoneCohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed
Started0099000
Completed0099000
Not completed0000000
Cohort3:Treatment Period 2(Up to 5 Days)
Participant flow — Cohort3:Treatment Period 2(Up to 5 Days)
MilestoneCohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed
Started0099000
Completed0099000
Not completed0000000
Cohort 3: Follow-up (Up to 10 Days)
Participant flow — Cohort 3: Follow-up (Up to 10 Days)
MilestoneCohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed
Started0099000
Completed0099000
Not completed0000000
Cohort4:Treatment Period 1(Up to 3 Days)
Participant flow — Cohort4:Treatment Period 1(Up to 3 Days)
MilestoneCohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed
Started0000653
Completed0000653
Not completed0000000
Cohort4:Washout Period 1(Up to 3 Days)
Participant flow — Cohort4:Washout Period 1(Up to 3 Days)
MilestoneCohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed
Started0000653
Completed0000653
Not completed0000000
Cohort4:Treatment Period 2(Up to 3 Days)
Participant flow — Cohort4:Treatment Period 2(Up to 3 Days)
MilestoneCohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed
Started0000653
Completed0000653
Not completed0000000
Cohort4:Washout Period 2(Up to 3 Days)
Participant flow — Cohort4:Washout Period 2(Up to 3 Days)
MilestoneCohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed
Started0000653
Completed0000653
Not completed0000000
Cohort4:Treatment Period 3(Up to 3 Days)
Participant flow — Cohort4:Treatment Period 3(Up to 3 Days)
MilestoneCohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed
Started0000653
Completed0000653
Not completed0000000
Cohort 4: Follow-up (Up to 7 Days)
Participant flow — Cohort 4: Follow-up (Up to 7 Days)
MilestoneCohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed
Started0000653
Completed0000653
Not completed0000000

Outcome measures

PrimaryCohort 1: Maximum Observed Concentration (Cmax) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric least square (LS) mean and 90 percent (%) confidence interval (CI) of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Micrograms per milliliter
Cohort 1: Maximum Observed Concentration (Cmax) of Gepotidacin in Plasma
Micrograms per milliliterCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Cohort 1: Maximum Observed Concentration (Cmax) of Gepotidacin in Plasma4.817 (4.006 to 5.793)4.548 (3.756 to 5.506)
Statistical analysis
  • Cohort 1: Gepotidacin 1500 mg vs Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg · Ratio of geometric ls mean: 0.944 · 90% CI 0.753 to 1.184
PrimaryCohort 1: Time to Reach Maximum Observed Concentration (Tmax) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Median · Hours
Cohort 1: Time to Reach Maximum Observed Concentration (Tmax) of Gepotidacin in Plasma
HoursCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Cohort 1: Time to Reach Maximum Observed Concentration (Tmax) of Gepotidacin in Plasma2.500 (1.00 to 4.00)2.500 (1.00 to 4.00)
Statistical analysis
  • Cohort 1: Gepotidacin 1500 mg vs Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg · Median difference (final values): -0.250 · 90% CI -0.750 to 0.742The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate.
PrimaryCohort 1: Terminal Phase Half-life (t1/2) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Hours
Cohort 1: Terminal Phase Half-life (t1/2) of Gepotidacin in Plasma
HoursCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Cohort 1: Terminal Phase Half-life (t1/2) of Gepotidacin in Plasma11.344 (10.282 to 12.516)12.415 (11.207 to 13.754)
Statistical analysis
  • Cohort 1: Gepotidacin 1500 mg vs Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg · Ratio of geometric ls mean: 1.094 · 90% CI 0.959 to 1.249
PrimaryCohort 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Hours*micrograms per milliliter
Cohort 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Gepotidacin in Plasma
Hours*micrograms per milliliterCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Cohort 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Gepotidacin in Plasma20.3 (17.7 to 23.3)23.4 (20.4 to 26.9)
Statistical analysis
  • Cohort 1: Gepotidacin 1500 mg vs Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg · Ratio of geometric ls mean: 1.157 · 90% CI 1.059 to 1.265
PrimaryCohort 1: AUC From Time 0 (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Hours* micrograms per milliliter
Cohort 1: AUC From Time 0 (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) of Gepotidacin in Plasma
Hours* micrograms per milliliterCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Cohort 1: AUC From Time 0 (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) of Gepotidacin in Plasma20.6 (18.0 to 23.6)23.9 (20.8 to 27.4)
Statistical analysis
  • Cohort 1: Gepotidacin 1500 mg vs Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg · Ratio of geometric ls mean: 1.158 · 90% CI 1.062 to 1.264
PrimaryCohort 2: Cmax of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Micrograms per milliliter
Cohort 2: Cmax of Gepotidacin in Plasma
Micrograms per milliliterCohort 2:Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
Cohort 2: Cmax of Gepotidacin in Plasma3.735 (3.209 to 4.347)2.728 (2.323 to 3.202)
Statistical analysis
  • Cohort 2:Period 1: Gepotidacin 1500 mg vs Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg · Ratio of geometric ls mean: 0.730 · 90% CI 0.635 to 0.840
PrimaryCohort 2: Lag Time Before Observation of Drug Concentrations (Tlag) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Median · Hours
Cohort 2: Lag Time Before Observation of Drug Concentrations (Tlag) of Gepotidacin in Plasma
HoursCohort 2:Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
Cohort 2: Lag Time Before Observation of Drug Concentrations (Tlag) of Gepotidacin in Plasma0.000 (0 to 1.00)0.000 (0 to 0.50)
Statistical analysis
  • Cohort 2:Period 1: Gepotidacin 1500 mg vs Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg · Median difference (final values): 0.000 · 90% CI 0.000 to 0.000The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate.
PrimaryCohort 2: Tmax of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Median · Hours
Cohort 2: Tmax of Gepotidacin in Plasma
HoursCohort 2:Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
Cohort 2: Tmax of Gepotidacin in Plasma2.500 (1.00 to 6.00)2.000 (1.00 to 4.00)
Statistical analysis
  • Cohort 2:Period 1: Gepotidacin 1500 mg vs Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg · Median difference (final values): -0.467 · 90% CI -1.000 to 0.492The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate
PrimaryCohort 2: AUC(0-t) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Hours*micrograms per milliliter
Cohort 2: AUC(0-t) of Gepotidacin in Plasma
Hours*micrograms per milliliterCohort 2:Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
Cohort 2: AUC(0-t) of Gepotidacin in Plasma19.0 (16.9 to 21.3)9.0 (8.0 to 10.2)
Statistical analysis
  • Cohort 2:Period 1: Gepotidacin 1500 mg vs Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg · Ratio of geometric ls mean: 0.476 · 90% CI 0.433 to 0.525
PrimaryCohort 2: AUC(0-infinity) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Hours*micrograms per milliliter
Cohort 2: AUC(0-infinity) of Gepotidacin in Plasma
Hours*micrograms per milliliterCohort 2:Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
Cohort 2: AUC(0-infinity) of Gepotidacin in Plasma19.3 (17.2 to 21.7)9.3 (8.2 to 10.4)
Statistical analysis
  • Cohort 2:Period 1: Gepotidacin 1500 mg vs Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg · Ratio of geometric ls mean: 0.478 · 90% CI 0.435 to 0.526
PrimaryCohort 3: Cmax of Digoxin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Picograms per milliliter
Cohort 3: Cmax of Digoxin in Plasma
Picograms per milliliterCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: Cmax of Digoxin in Plasma1553.135 (1318.390 to 1829.676)2381.259 (2013.503 to 2816.185)
Statistical analysis
  • Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg vs Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg · Ratio of geometric ls mean: 1.533 · 90% CI 1.274 to 1.845
PrimaryCohort 3: Tlag of Digoxin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Median · Hours
Cohort 3: Tlag of Digoxin in Plasma
HoursCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: Tlag of Digoxin in Plasma0.000 (0 to 0)0.000 (0 to 0)
Statistical analysis
  • Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg vs Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg · Median difference (final values): 0.000 · 90% CI 0.000 to 0.000The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate.
PrimaryCohort 3: Tmax of Digoxin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Median · Hours
Cohort 3: Tmax of Digoxin in Plasma
HoursCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: Tmax of Digoxin in Plasma2.000 (0.50 to 4.00)1.275 (0.50 to 4.00)
Statistical analysis
  • Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg vs Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg · Median difference (final values): -0.500 · 90% CI -1.000 to -0.233The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate.
PrimaryCohort 3: AUC(0-t) of Digoxin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Hours*picograms per milliliter
Cohort 3: AUC(0-t) of Digoxin in Plasma
Hours*picograms per milliliterCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: AUC(0-t) of Digoxin in Plasma25353.1 (22490.9 to 28579.6)30842.3 (27241.5 to 34919.0)
Statistical analysis
  • Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg vs Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg · Ratio of geometric ls mean: 1.217 · 90% CI 1.085 to 1.363
PrimaryCohort 3: AUC(0-infinity) of Digoxin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Hours*picograms per milliliter
Cohort 3: AUC(0-infinity) of Digoxin in Plasma
Hours*picograms per milliliterCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: AUC(0-infinity) of Digoxin in Plasma30743.6 (27425.5 to 34463.1)34456.5 (30652.1 to 38733.1)
Statistical analysis
  • Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg vs Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg · Ratio of geometric ls mean: 1.121 · 90% CI 0.983 to 1.278
PrimaryCohort 3: Cmax of Midazolam in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Nanograms per milliliter
Cohort 3: Cmax of Midazolam in Plasma
Nanograms per milliliterCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: Cmax of Midazolam in Plasma5.238 (4.436 to 6.185)6.507 (5.492 to 7.711)
Statistical analysis
  • Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg vs Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg · Ratio of geometric ls mean: 1.242 · 90% CI 1.046 to 1.475
PrimaryCohort 3: Tlag of Midazolam in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Median · Hours
Cohort 3: Tlag of Midazolam in Plasma
HoursCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: Tlag of Midazolam in Plasma0.000 (0 to 0)0.000 (0 to 0)
Statistical analysis
  • Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg vs Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg · Median difference (final values): 0.000 · 90% CI 0.000 to 0.000The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate.
PrimaryCohort 3: Tmax of Midazolam in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Median · Hours
Cohort 3: Tmax of Midazolam in Plasma
HoursCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: Tmax of Midazolam in Plasma0.650 (0.50 to 2.50)0.500 (0.50 to 4.00)
Statistical analysis
  • Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg vs Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg · Median difference (final values): 0.000 · 90% CI -0.250 to 0.800The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate.
PrimaryCohort 3: AUC(0-t) of Midazolam in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Hours*nanograms per milliliter
Cohort 3: AUC(0-t) of Midazolam in Plasma
Hours*nanograms per milliliterCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: AUC(0-t) of Midazolam in Plasma23.3 (19.5 to 27.9)44.8 (37.4 to 53.8)
Statistical analysis
  • Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg vs Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg · Ratio of geometric ls mean: 1.923 · 90% CI 1.622 to 2.278
PrimaryCohort 3: AUC(0-infinity) of Midazolam in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Hours*nanograms per milliliter
Cohort 3: AUC(0-infinity) of Midazolam in Plasma
Hours*nanograms per milliliterCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: AUC(0-infinity) of Midazolam in Plasma24.9 (21.1 to 29.6)47.4 (39.9 to 56.4)
Statistical analysis
  • Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg vs Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg · Ratio of geometric ls mean: 1.902 · 90% CI 1.619 to 2.234
PrimaryCohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Micrograms per milliliter
Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma
Micrograms per milliliterCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg Fasted
Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma5.436 ± 27.85.143 ± 34.2
PrimaryCohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Median · Hours
Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma
HoursCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg Fasted
Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma2.000 (1.50 to 4.00)1.500 (1.00 to 4.00)
PrimaryCohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 24 Hours Post-dose (AUC[0-24]) of Gepotidacin Following Single Dose of 1500 mg in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 24 Hours Post-dose (AUC[0-24]) of Gepotidacin Following Single Dose of 1500 mg in Plasma
Hours*micrograms per milliliterCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg Fasted
Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 24 Hours Post-dose (AUC[0-24]) of Gepotidacin Following Single Dose of 1500 mg in Plasma20.9 ± 16.819.0 ± 12.9
PrimaryCohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 48 Hours Post-dose (AUC[0-48]) of Gepotidacin Following Single Dose of 1500 mg in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 48 Hours Post-dose (AUC[0-48]) of Gepotidacin Following Single Dose of 1500 mg in Plasma
Hours*micrograms per milliliterCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg Fasted
Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 48 Hours Post-dose (AUC[0-48]) of Gepotidacin Following Single Dose of 1500 mg in Plasma21.9 ± 16.020.0 ± 13.2
PrimaryCohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma
Hours*micrograms per milliliterCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg Fasted
Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma21.9 ± 16.020.0 ± 13.2
PrimaryCohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma
Hours*micrograms per milliliterCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg Fasted
Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma22.3 ± 15.520.4 ± 13.3
PrimaryCohort 4: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Reported as:
Geometric mean · Micrograms per milliliter
Cohort 4: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State
Micrograms per milliliterCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State11.204 ± 45.0
PrimaryCohort 4: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Reported as:
Median · Hours
Cohort 4: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State
HoursCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State2.000 (1.00 to 4.00)
PrimaryCohort 4: AUC From Time 0 (Predose) to Time Tau (AUC[0-tau]) of Gepotidacin in Plasma After the First Dose of 3000 Mg-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 4: AUC From Time 0 (Predose) to Time Tau (AUC[0-tau]) of Gepotidacin in Plasma After the First Dose of 3000 Mg-Fed State
Hours*micrograms per milliliterCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: AUC From Time 0 (Predose) to Time Tau (AUC[0-tau]) of Gepotidacin in Plasma After the First Dose of 3000 Mg-Fed State37.3 ± 25.4
PrimaryCohort 4: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Reported as:
Geometric mean · Micrograms per milliliter
Cohort 4: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
Micrograms per milliliterCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State12.363 ± 21.3
PrimaryCohort 4: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Reported as:
Median · Hours
Cohort 4: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
HoursCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State2.000 (1.00 to 3.00)
PrimaryCohort 4: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Evening Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 4: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Evening Dose)-Fed State
Hours*micrograms per milliliterCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Evening Dose)-Fed State46.7 ± 23.1
PrimaryCohort 4: Accumulation Ratio Based on Cmax (RoCmax) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Reported as:
Geometric mean · Ratio
Cohort 4: Accumulation Ratio Based on Cmax (RoCmax) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
RatioCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: Accumulation Ratio Based on Cmax (RoCmax) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State1.103 ± 39.3
PrimaryCohort 4: Accumulation Ratio Based on AUC(0-tau) (RoAUC) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) after the second dose, where 0 is the timepoint prior to second dose, divided by AUC(0-tau) after the first dose, where 0 is the predose timepoint prior to the first dose.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Reported as:
Geometric mean · Ratio
Cohort 4: Accumulation Ratio Based on AUC(0-tau) (RoAUC) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
RatioCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: Accumulation Ratio Based on AUC(0-tau) (RoAUC) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State1.254 ± 13.1
PrimaryCohort 4: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24 Hours post-dose in Treatment Period 3
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 4: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
Hours*micrograms per milliliterCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State84.6 ± 23.1
PrimaryCohort 4: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48 Hours post-dose in Treatment Period 3
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 4: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
Hours*micrograms per milliliterCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State90.8 ± 22.9
PrimaryCohort 4: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 4: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
Hours*micrograms per milliliterCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State91.4 ± 23.0
PrimaryCohort 4: Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE)

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.

Time frame:
Up to 22 days
Reported as:
Count of participants · Participants
Cohort 4: Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE)
ParticipantsCohort 4: PlaceboCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg FastedCohort 4: Gepotidacin 3000 mg Fed
Any SAE0000
Any non-SAE0124
PrimaryCohort 4: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, Erythrocyte Mean Corpuscular Hemoglobin (MCH), Erythrocyte Mean Corpuscular Volume (MCV), Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose laboratory (lab) value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 (%). High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

Time frame:
Up to 22 days
Reported as:
Count of participants · Participants
Cohort 4: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
ParticipantsCohort 4: PlaceboCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg FastedCohort 4: Gepotidacin 3000 mg Fed
Basophils; To Low0000
Basophils; To Normal or No Change311910
Basophils; To High0021
Eosinophils; To Low0000
Eosinophils; To Normal or No Change3101010
Eosinophils; To High0111
MCH; To Low0000
MCH; To Normal or No Change3111111
MCH; To High0000
MCV; To Low0000
MCV; To Normal or No Change210109
MCV; To High1112
Erythrocytes; To Low0001
Erythrocytes; To Normal or No Change3101110
Erythrocytes; To High0100
Hematocrit; To Low0000
Hematocrit; To Normal or No Change3101110
Hematocrit; To High0101
Hemoglobin; To Low0000
Hemoglobin; To Normal or No Change3101111
Hemoglobin; To High0100
Leukocytes; To Low0001
Leukocytes; To Normal or No Change3111110
Leukocytes; To High0000
Lymphocytes; To Low0000
Lymphocytes; To Normal or No Change3111111
Lymphocytes; To High0000
Monocytes; To Low0000
Monocytes; To Normal or No Change3111111
Monocytes; To High0000
Neutrophils; To Low0011
Neutrophils; To Normal or No Change3111010
Neutrophils; To High0000
Platelets; To Low0001
Platelets; To Normal or No Change3111110
Platelets; To High0000
PrimaryCohort 4: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase (Alk Phos), Aspartate Aminotransferase (AST), Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, Blood Urea Nitrogen (BUN). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

Time frame:
Up to 22 days
Reported as:
Count of participants · Participants
Cohort 4: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
ParticipantsCohort 4: PlaceboCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg FastedCohort 4: Gepotidacin 3000 mg Fed
ALT; To Low0000
ALT; To Normal or No Change3111111
ALT; To High0000
Albumin; To Low1000
Albumin; To Normal or No Change2111111
Albumin; To High0000
Alk Phos; To Low0000
Alk Phos; To Normal or No Change3111111
Alk Phos; To High0000
AST; To Low0000
AST; To Normal or No Change3111111
AST; To High0000
Bilirubin; To Low0000
Bilirubin; To Normal or No Change2111111
Bilirubin; To High1000
Calcium; To Low0000
Calcium; To Normal or No Change3111111
Calcium; To High0000
Carbon Dioxide; To Low0010
Carbon Dioxide; To Normal or No Change3111011
Carbon Dioxide; To High0000
Chloride; To Low0000
Chloride; To Normal or No Change3111111
Chloride; To High0000
Creatine Kinase; To Low1001
Creatine Kinase; To Normal or No Change211119
Creatine Kinase; To High0001
Creatinine; To Low0000
Creatinine; To Normal or No Change3111111
Creatinine;To High0000
Direct Bilirubin; To Low0000
Direct Bilirubin; To Normal or No Change2111111
Direct Bilirubin; To High1000
Glucose; To Low0000
Glucose; To Normal or No Change3111111
Glucose; To High0000
Magnesium; To Low0000
Magnesium; To Normal or No Change3111111
Magnesium; To High0000
Potassium; To Low0000
Potassium; To Normal or No Change2111111
Potassium; To High1000
Protein; To Low0000
Protein; To Normal or No Change3111111
Protein; To High0000
Sodium; To Low0000
Sodium; To Normal or No Change3111111
Sodium; To High0000
BUN; To Low0000
BUN; To Normal or No Change3111111
BUN; To High0000
PrimaryCohort 4: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline

Urine samples were collected at indicated time points for the analysis of urinalysis parameters including potential of hydrogen (pH) of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

Time frame:
Up to 22 days
Reported as:
Count of participants · Participants
Cohort 4: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
ParticipantsCohort 4: PlaceboCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg FastedCohort 4: Gepotidacin 3000 mg Fed
Bilirubin; To Normal or No Change3111111
Bilirubin; To Abnormal0000
Glucose; To Normal or No Change3111111
Glucose; To Abnormal0000
Ketones; To Normal or No Change2111111
Ketones; To Abnormal1000
Leukocyte Esterase; To Normal or No Change29119
Leukocyte Esterase; To Abnormal1202
Nitrite; To Normal or No Change3111110
Nitrite; To Abnormal0001
Occult Blood; To Normal or No Change2111010
Occult Blood; To Abnormal1011
Protein; To Normal or No Change3111111
Protein; To Abnormal0000
pH; To Low0000
pH; To Normal or No Change3111111
pH; To High0000
Specific Gravity; To Low0000
Specific Gravity; To Normal or No Change3111111
Specific Gravity; To High0000
PrimaryCohort 4: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline

Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

Time frame:
Up to 22 days
Reported as:
Count of participants · Participants
Cohort 4: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
ParticipantsCohort 4: PlaceboCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg FastedCohort 4: Gepotidacin 3000 mg Fed
DBP; To Low0100
DBP; To Normal or No Change3101111
DBP; To High0000
SBP; To Low0110
SBP; To Normal or No Change3101011
SBP; To High0000
Pulse rate; To Low0000
Pulse rate; To Normal or No Change3111111
Pulse rate; To High0000
PrimaryCohort 4: Number of Participants With Any Increase in Maximum Post-Baseline Electrocardiogram (ECG) Parameter Corrected QT (QTc) Interval

A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of \>450 milliseconds in corrected QT interval using the Bazett formula (QTcB) Interval and corrected QT interval using the Fridericia formula (QTcF) Interval has been reported.

Time frame:
Up to 22 days
Reported as:
Count of participants · Participants
Cohort 4: Number of Participants With Any Increase in Maximum Post-Baseline Electrocardiogram (ECG) Parameter Corrected QT (QTc) Interval
ParticipantsCohort 4: PlaceboCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg FastedCohort 4: Gepotidacin 3000 mg Fed
QTcB Interval1839
QTcF Interval1102
PrimaryCohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Micrograms per milliliter
Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
Micrograms per milliliterCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg Fasted
Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants5.421 (4.610 to 6.374)5.158 (4.386 to 6.065)
Statistical analysis
  • Cohort 4: Gepotidacin 1500 mg Fed vs Cohort 4: Gepotidacin 1500 mg Fasted · Ratio of geometric ls mean: 1.051 · 90% CI 0.824 to 1.340
PrimaryCohort 4: Tlag of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Median · Hours
Cohort 4: Tlag of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
HoursCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg Fasted
Cohort 4: Tlag of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants0.000 (0 to 0.50)0.000 (0 to 0)
Statistical analysis
  • Cohort 4: Gepotidacin 1500 mg Fed vs Cohort 4: Gepotidacin 1500 mg Fasted · Median difference (final values): 0.000 · 90% CI 0.000 to 0.250The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate.
PrimaryCohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Median · Hours
Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
HoursCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg Fasted
Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants2.000 (1.50 to 4.00)1.500 (1.00 to 4.00)
Statistical analysis
  • Cohort 4: Gepotidacin 1500 mg Fed vs Cohort 4: Gepotidacin 1500 mg Fasted · Median difference (final values): 0.500 · 90% CI -0.500 to 1.250The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate.
PrimaryCohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Hours*Micrograms per milliliter
Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
Hours*Micrograms per milliliterCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg Fasted
Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants21.9 (20.3 to 23.7)20.0 (18.5 to 21.6)
Statistical analysis
  • Cohort 4: Gepotidacin 1500 mg Fed vs Cohort 4: Gepotidacin 1500 mg Fasted · Ratio of geometric ls mean: 1.094 · 90% CI 0.987 to 1.212
PrimaryCohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Hours*Micrograms per milliliter
Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
Hours*Micrograms per milliliterCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg Fasted
Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants22.3 (20.7 to 24.1)20.4 (18.9 to 22.0)
Statistical analysis
  • Cohort 4: Gepotidacin 1500 mg Fed vs Cohort 4: Gepotidacin 1500 mg Fasted · Ratio of geometric ls mean: 1.095 · 90% CI 0.991 to 1.209
SecondaryCohort 1: AUC (0-24) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 1: AUC (0-24) of Gepotidacin in Plasma
Hours*micrograms per milliliterCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Cohort 1: AUC (0-24) of Gepotidacin in Plasma19.3 ± 32.621.9 ± 29.7
SecondaryCohort 1: AUC(0-48) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 1: AUC(0-48) of Gepotidacin in Plasma
Hours*micrograms per milliliterCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Cohort 1: AUC(0-48) of Gepotidacin in Plasma20.3 ± 31.423.0 ± 28.4
SecondaryCohort 1: Tlag of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Median · Hours
Cohort 1: Tlag of Gepotidacin in Plasma
HoursCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Cohort 1: Tlag of Gepotidacin in Plasma0.000 (0 to 0.50)0.000 (0 to 0)
Statistical analysis
  • Cohort 1: Gepotidacin 1500 mg vs Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg · Median difference (final values): 0.000 · 90% CI -0.250 to 0.000The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate.
SecondaryCohort 1: Apparent Volume of Distribution (Vz/F) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Liters
Cohort 1: Apparent Volume of Distribution (Vz/F) of Gepotidacin in Plasma
LitersCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Cohort 1: Apparent Volume of Distribution (Vz/F) of Gepotidacin in Plasma1190.16 ± 34.01143.29 ± 30.6
SecondaryCohort 1: Apparent Oral Clearance (CL/F) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Liters per Hour
Cohort 1: Apparent Oral Clearance (CL/F) of Gepotidacin in Plasma
Liters per HourCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Cohort 1: Apparent Oral Clearance (CL/F) of Gepotidacin in Plasma72.72 ± 31.264.14 ± 28.0
SecondaryCohort 1: Total Unchanged Drug (Ae Total) of Gepotidacin in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2
Reported as:
Geometric least squares mean · Milligrams
Cohort 1: Total Unchanged Drug (Ae Total) of Gepotidacin in Urine
MilligramsCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Cohort 1: Total Unchanged Drug (Ae Total) of Gepotidacin in Urine337.92 (281.14 to 406.16)410.10 (343.16 to 490.08)
Statistical analysis
  • Cohort 1: Gepotidacin 1500 mg vs Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg · Ratio of geometric ls mean: 1.214 · 90% CI 1.000 to 1.473
SecondaryCohort 1: AUC(0-24) of Gepotidacin in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours Post-dose in each Treatment periods 1 and 2
Reported as:
Geometric least squares mean · Hours*micrograms per milliliter
Cohort 1: AUC(0-24) of Gepotidacin in Urine
Hours*micrograms per milliliterCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Cohort 1: AUC(0-24) of Gepotidacin in Urine3292.1 (2639.2 to 4106.5)3612.4 (2888.5 to 4517.7)
Statistical analysis
  • Cohort 1: Gepotidacin 1500 mg vs Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg · Ratio of geometric ls mean: 1.097 · 90% CI 0.948 to 1.270
SecondaryCohort 1: AUC(0-48) of Gepotidacin in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2
Reported as:
Geometric least squares mean · Hours*micrograms per milliliter
Cohort 1: AUC(0-48) of Gepotidacin in Urine
Hours*micrograms per milliliterCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Cohort 1: AUC(0-48) of Gepotidacin in Urine3578.2 (2890.1 to 4430.0)3831.1 (3087.7 to 4753.4)
Statistical analysis
  • Cohort 1: Gepotidacin 1500 mg vs Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg · Ratio of geometric ls mean: 1.071 · 90% CI 0.939 to 1.221
SecondaryCohort 1: Renal Clearance (CLr) of Gepotidacin

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2
Reported as:
Geometric least squares mean · Liters per Hour
Cohort 1: Renal Clearance (CLr) of Gepotidacin
Liters per HourCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Cohort 1: Renal Clearance (CLr) of Gepotidacin16.06 (14.18 to 18.18)17.59 (15.62 to 19.81)
Statistical analysis
  • Cohort 1: Gepotidacin 1500 mg vs Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg · Ratio of geometric ls mean: 1.096 · 90% CI 0.930 to 1.292
SecondaryCohort 1: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.

Time frame:
0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment periods 1 and 2
Reported as:
Geometric mean · Milligrams
Cohort 1: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin
MilligramsCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Ae (0-2), n=14, 1328.66 ± 185.9NA ± NA
Ae (2-4), n=14, 1289.18 ± 120.8142.99 ± 42.7
Ae (4-6), n=14, 1350.52 ± 119.182.77 ± 44.0
Ae (6-8); n=14, 1334.38 ± 56.246.22 ± 55.3
Ae (8-12), n=12, 1329.90 ± 38.330.97 ± 38.0
Ae (12-24), n=14, 1325.44 ± 38.122.04 ± 121.3
Ae (24-36), n=14, 1310.88 ± 43.18.76 ± 89.6
Ae (36-48), n=14, 134.50 ± 39.34.08 ± 88.5
SecondaryCohort 1: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 percent (%).

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2
Reported as:
Geometric mean · Percent dose excreted
Cohort 1: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin
Percent dose excretedCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Cohort 1: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin22.72 ± 53.226.90 ± 21.3
SecondaryCohort 1: Number of Participants With SAE and Non-SAE

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.

Time frame:
Up to 17 days
Reported as:
Count of participants · Participants
Cohort 1: Number of Participants With SAE and Non-SAE
ParticipantsCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Any SAE00
Any non-SAE00
SecondaryCohort 1: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 %. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

Time frame:
Up to 17 days
Reported as:
Count of participants · Participants
Cohort 1: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
ParticipantsCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Basophils; To Low00
Basophils; To Normal or No Change1411
Basophils; To High02
Eosinophils; To Low00
Eosinophils; To Normal or No Change1413
Eosinophils; To High00
MCH; To Low00
MCH; To Normal or No Change1413
MCH; To High00
MCV; To Low00
MCV; To Normal or No Change1313
MCV; To High10
Erythrocytes; To Low02
Erythrocytes; To Normal or No Change1411
Erythrocytes; To High00
Hematocrit; To Low01
Hematocrit; To Normal or No Change1312
Hematocrit; To High10
Hemoglobin; To Low00
Hemoglobin; To Normal or No Change1413
Hemoglobin; To High00
Leukocytes; To Low00
Leukocytes; To Normal or No Change1313
Leukocytes; To High10
Lymphocytes; To Low00
Lymphocytes; To Normal or No Change1412
Lymphocytes; To High01
Monocytes; To Low00
Monocytes; To Normal or No Change1313
Monocytes; To High10
Neutrophils; To Low01
Neutrophils; To Normal or No Change1312
Neutrophils; To High10
Platelets; To Low00
Platelets; To Normal or No Change1413
Platelets; To High00
SecondaryCohort 1: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

Time frame:
Up to 17 days
Reported as:
Count of participants · Participants
Cohort 1: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
ParticipantsCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
ALT; To Low00
ALT; To Normal or No Change1411
ALT; To High02
Albumin; To Low01
Albumin; To Normal or No Change1412
Albumin; To High00
Alk Phos; To Low00
Alk Phos; To Normal or No Change1413
Alk Phos; To High00
AST; To Low00
AST; To Normal or No Change1412
AST; To High01
Bilirubin; To Low01
Bilirubin; To Normal or No Change1412
Bilirubin; To High00
Calcium; To Low00
Calcium; To Normal or No Change1413
Calcium; To High00
Carbon Dioxide; To Low10
Carbon Dioxide; To Normal or No Change1313
Carbon Dioxide; To High00
Chloride; To Low00
Chloride; To Normal or No Change1412
Chloride; To High01
Creatine Kinase; To Low10
Creatine Kinase; To Normal or No Change1313
Creatine Kinase; To High00
Creatinine; To Low00
Creatinine; To Normal or No Change1410
Creatinine; To High03
Direct Bilirubin; To Low00
Direct Bilirubin; To Normal or No Change1413
Direct Bilirubin; To High00
Glucose; To Low00
Glucose; To Normal or No Change1413
Glucose; To High00
Magnesium; To Low00
Magnesium; To Normal or No Change1413
Magnesium; To High00
Potassium; To Low00
Potassium; To Normal or No Change1412
Potassium; To High01
Protein; To Low00
Protein; To Normal or No Change1413
Protein; To High00
Sodium; To Low00
Sodium; To Normal or No Change1413
Sodium; To High00
BUN; To Low00
BUN; To Normal or No Change1413
BUN; To High00
SecondaryCohort 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline

Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

Time frame:
Up to 17 days
Reported as:
Count of participants · Participants
Cohort 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
ParticipantsCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
Bilirubin; To Normal or No Change1413
Bilirubin; To Abnormal00
Glucose; To Normal or No Change1413
Glucose; To Abnormal00
Ketones; To Normal or No Change1413
Ketones; To Abnormal00
Leukocyte Esterase; To Normal or No Change1213
Leukocyte Esterase; To Abnormal20
Nitrite; To Normal or No Change1413
Nitrite; To Abnormal00
Occult Blood; To Normal or No Change1311
Occult Blood; To Abnormal12
Protein; To Normal or No Change1413
Protein; To Abnormal00
pH; To Low00
pH; To Normal or No Change1413
pH; To High00
Specific Gravity; To Low00
Specific Gravity; To Normal or No Change1313
Specific Gravity; To High10
SecondaryCohort 1: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline

Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

Time frame:
Up to 17 days
Reported as:
Count of participants · Participants
Cohort 1: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
ParticipantsCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
DBP; To Low00
DBP; To Normal or No Change1413
DBP; To High00
SBP; To Low00
SBP; To Normal or No Change1413
SBP; To High00
Pulse rate; To Low00
Pulse rate; To Normal or No Change1413
Pulse rate; To High00
SecondaryCohort 1: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval

A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of \>450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported.

Time frame:
Up to 17 days
Reported as:
Count of participants · Participants
Cohort 1: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval
ParticipantsCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg
QTcB Interval34
QTcF Interval01
SecondaryCohort 2: AUC(0-24) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 2: AUC(0-24) of Gepotidacin in Plasma
Hours*micrograms per milliliterCohort 2:Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
Cohort 2: AUC(0-24) of Gepotidacin in Plasma17.9 ± 28.68.9 ± 29.6
SecondaryCohort 2: AUC(0-48) of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 2: AUC(0-48) of Gepotidacin in Plasma
Hours*micrograms per milliliterCohort 2:Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
Cohort 2: AUC(0-48) of Gepotidacin in Plasma19.0 ± 27.79.5 ± 28.5
SecondaryCohort 2: T1/2 of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours
Cohort 2: T1/2 of Gepotidacin in Plasma
HoursCohort 2:Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
Cohort 2: T1/2 of Gepotidacin in Plasma10.882 ± 25.510.972 ± 17.2
SecondaryCohort 2: Vz/F of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Liters
Cohort 2: Vz/F of Gepotidacin in Plasma
LitersCohort 2:Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
Cohort 2: Vz/F of Gepotidacin in Plasma1217.45 ± 37.02460.46 ± 39.2
SecondaryCohort 2: CL/F of Gepotidacin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Liters per Hour
Cohort 2: CL/F of Gepotidacin in Plasma
Liters per HourCohort 2:Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
Cohort 2: CL/F of Gepotidacin in Plasma77.55 ± 27.6155.43 ± 27.9
SecondaryCohort 2: Ae Total of Gepotidacin in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Milligrams
Cohort 2: Ae Total of Gepotidacin in Urine
MilligramsCohort 2:Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
Cohort 2: Ae Total of Gepotidacin in Urine312.73 (286.95 to 340.82)156.05 (141.81 to 171.72)
Statistical analysis
  • Cohort 2:Period 1: Gepotidacin 1500 mg vs Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg · Ratio of geometric ls mean: 0.499 · 90% CI 0.441 to 0.565
SecondaryCohort 2: AUC(0-24) of Gepotidacin in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Hours*micrograms per milliliter
Cohort 2: AUC(0-24) of Gepotidacin in Urine
Hours*micrograms per milliliterCohort 2:Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
Cohort 2: AUC(0-24) of Gepotidacin in Urine3081.3 (2327.4 to 4079.5)1352.4 (1014.2 to 1803.4)
Statistical analysis
  • Cohort 2:Period 1: Gepotidacin 1500 mg vs Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg · Ratio of geometric ls mean: 0.439 · 90% CI 0.370 to 0.521
SecondaryCohort 2: AUC(0-48) of Gepotidacin in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Hours*micrograms per milliliter
Cohort 2: AUC(0-48) of Gepotidacin in Urine
Hours*micrograms per milliliterCohort 2:Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
Cohort 2: AUC(0-48) of Gepotidacin in Urine3370.1 (2571.4 to 4417.0)1476.8 (1119.2 to 1948.6)
Statistical analysis
  • Cohort 2:Period 1: Gepotidacin 1500 mg vs Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg · Ratio of geometric ls mean: 0.438 · 90% CI 0.372 to 0.516
SecondaryCohort 2: CLr of Gepotidacin

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Liters per Hour
Cohort 2: CLr of Gepotidacin
Liters per HourCohort 2:Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
Cohort 2: CLr of Gepotidacin16.49 (15.02 to 18.09)17.07 (15.47 to 18.84)
Statistical analysis
  • Cohort 2:Period 1: Gepotidacin 1500 mg vs Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg · Ratio of geometric ls mean: 1.036 · 90% CI 0.950 to 1.129
SecondaryCohort 2: Ae(t1-t2) of Gepotidacin

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.

Time frame:
0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Milligrams
Cohort 2: Ae(t1-t2) of Gepotidacin
MilligramsCohort 2:Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
Ae (0-2)12.67 ± 567.5NA ± NA
Ae (2-4)79.84 ± 65.655.81 ± 47.4
Ae (4-6)67.48 ± 44.321.66 ± 66.4
Ae (6-8)33.92 ± 50.513.82 ± 56.1
Ae (8-12)27.59 ± 63.19.19 ± 50.7
Ae (12-24)21.17 ± 79.211.51 ± 36.4
Ae (24-36)11.04 ± 77.94.74 ± 42.7
Ae (36-48)3.61 ± 90.32.75 ± 31.8
SecondaryCohort 2: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Percent dose excreted
Cohort 2: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin
Percent dose excretedCohort 2:Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
Cohort 2: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin20.85 ± 16.910.42 ± 25.4
SecondaryCohort 2: Number of Participants With SAE and Non-SAE

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.

Time frame:
Up to 26 days
Reported as:
Count of participants · Participants
Cohort 2: Number of Participants With SAE and Non-SAE
ParticipantsCohort 2: Period 1: Gepotidacin 1500 mgCohort 2: Period 2 (Days 1 to 7) Rifampicin 600 mgCohort 2: Period 2 (Days 8 to 9) Gepotidacin 1500 mg + Rifampicin 600 mg
Any SAE000
Any non-SAE322
SecondaryCohort 2: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

Time frame:
Up to 26 days
Reported as:
Count of participants · Participants
Cohort 2: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
ParticipantsCohort 2: Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
Basophils; To Low00
Basophils; To Normal or No Change1716
Basophils; To High01
Eosinophils; To Low00
Eosinophils; To Normal or No Change1514
Eosinophils; To High23
MCH; To Low00
MCH; To Normal or No Change1717
MCH; To High00
MCV; To Low00
MCV; To Normal or No Change1717
MCV; To High00
Erythrocytes; To Low00
Erythrocytes; To Normal or No Change1717
Erythrocytes; To High00
Hematocrit; To Low00
Hematocrit; To Normal or No Change1415
Hematocrit; To High32
Hemoglobin; To Low00
Hemoglobin; To Normal or No Change1717
Hemoglobin; To High00
Leukocytes; To Low01
Leukocytes; To Normal or No Change1716
Leukocytes; To High00
Lymphocytes; To Low00
Lymphocytes; To Normal or No Change1715
Lymphocytes; To High02
Monocytes; To Low13
Monocytes; To Normal or No Change1514
Monocytes; To High10
Neutrophils; To Low04
Neutrophils; To Normal or No Change1713
Neutrophils; To High00
Platelets; To Low00
Platelets; To Normal or No Change1716
Platelets; To High01
SecondaryCohort 2: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

Time frame:
Up to 26 days
Reported as:
Count of participants · Participants
Cohort 2: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
ParticipantsCohort 2: Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
ALT; To Low00
ALT; To Normal or No Change1715
ALT; To High02
Albumin; To Low00
Albumin; To Normal or No Change1717
Albumin; To High00
Alk Phos; To Low00
Alk Phos; To Normal or No Change1717
Alk Phos; To High00
AST; To Low00
AST; To Normal or No Change1716
AST; To High01
Bilirubin; To Low02
Bilirubin; To Normal or No Change1715
Bilirubin; To High00
Calcium; To Low00
Calcium; To Normal or No Change1717
Calcium; To High00
Carbon Dioxide; To Low03
Carbon Dioxide; To Normal or No Change1714
Carbon Dioxide; To High00
Chloride; To Low00
Chloride; To Normal or No Change1717
Chloride; To High00
Creatine Kinase; To Low00
Creatine Kinase; To Normal or No Change1717
Creatine Kinase; To High00
Creatinine; To Low00
Creatinine; To Normal or No Change1616
Creatinine; To High11
Direct Bilirubin; To Low00
Direct Bilirubin; To Normal or No Change1717
Direct Bilirubin; To High00
Glucose; To Low00
Glucose; To Normal or No Change1716
Glucose; To High01
Magnesium; To Low00
Magnesium; To Normal or No Change1717
Magnesium; To High00
Potassium; To Low00
Potassium; To Normal or No Change1615
Potassium; To High12
Protein; To Low00
Protein; To Normal or No Change1717
Protein; To High00
Sodium; To Low00
Sodium; To Normal or No Change1717
Sodium; To High00
BUN; To Low00
BUN; To Normal or No Change1717
BUN; To High00
SecondaryCohort 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline

Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

Time frame:
Up to 26 days
Reported as:
Count of participants · Participants
Cohort 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
ParticipantsCohort 2: Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
Bilirubin; To Normal or No Change1716
Bilirubin; To Abnormal00
Glucose; To Normal or No Change1716
Glucose; To Abnormal00
Ketones; To Normal or No Change1716
Ketones; To Abnormal00
Leukocyte Esterase; To Normal or No Change1614
Leukocyte Esterase; To Abnormal12
Nitrite; To Normal or No Change1715
Nitrite; To Abnormal01
Occult Blood; To Normal or No Change1714
Occult Blood; To Abnormal02
Protein; To Normal or No Change1716
Protein; To Abnormal00
pH; To Low00
pH; To Normal or No Change1716
pH; To High00
Specific Gravity; To Low00
Specific Gravity; To Normal or No Change1415
Specific Gravity; To High31
SecondaryCohort 2: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline

Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

Time frame:
Up to 26 days
Reported as:
Count of participants · Participants
Cohort 2: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
ParticipantsCohort 2: Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
DBP; To Low00
DBP; To Normal or No Change1614
DBP; To High10
SBP; To Low00
SBP; To Normal or No Change1714
SBP; To High00
Pulse rate; To Low00
Pulse rate; To Normal or No Change1714
Pulse rate; To High00
SecondaryCohort 2: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval

A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of \>450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported.

Time frame:
Up to 26 days
Reported as:
Count of participants · Participants
Cohort 2: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval
ParticipantsCohort 2: Period 1: Gepotidacin 1500 mgCohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg
QTcB Interval22
QTcF Interval01
SecondaryCohort 3: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Micrograms per milliliter
Cohort 3: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)
Micrograms per milliliterCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)7.867 ± 36.8
SecondaryCohort 3: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Median · Hours
Cohort 3: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)
HoursCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)2.500 (1.00 to 4.07)
SecondaryCohort 3: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Median · Hours
Cohort 3: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)
HoursCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)0.250 (0 to 1.00)
SecondaryCohort 3: AUC(0-tau) of Gepotidacin in Plasma First Dose of 3000 mg (First Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 3: AUC(0-tau) of Gepotidacin in Plasma First Dose of 3000 mg (First Dose)
Hours*micrograms per milliliterCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: AUC(0-tau) of Gepotidacin in Plasma First Dose of 3000 mg (First Dose)29.8 ± 30.8
SecondaryCohort 3: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Micrograms per milliliter
Cohort 3: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
Micrograms per milliliterCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)10.051 ± 47.7
SecondaryCohort 3: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Median · Hours
Cohort 3: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
HoursCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)2.000 (1.00 to 6.00)
SecondaryCohort 3: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours* micrograms per milliliter
Cohort 3: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
Hours* micrograms per milliliterCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)41.9 ± 30.2
SecondaryCohort 3: RoCmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Ratio
Cohort 3: RoCmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
RatioCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: RoCmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)1.278 ± 54.4
SecondaryCohort 3: RoAUC of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) after the second dose, where 0 is the timepoint prior to second dose, divided by AUC(0-tau) after the first dose, where 0 is the predose timepoint prior to the first dose.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Ratio
Cohort 3: RoAUC of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
RatioCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: RoAUC of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)1.406 ± 27.5
SecondaryCohort 3: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 3: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
Hours*micrograms per milliliterCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)73.2 ± 26.8
SecondaryCohort 3: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 3: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
Hours*micrograms per milliliterCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)81.2 ± 25.9
SecondaryCohort 3: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 3: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
Hours*micrograms per milliliterCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)85.2 ± 20.1
SecondaryCohort 3: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Liters
Cohort 3: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
LitersCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)959.42 ± 30.0
SecondaryCohort 3: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Liters per Hour
Cohort 3: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
Liters per HourCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)69.99 ± 20.1
SecondaryCohort 3: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose+ Second Dose)

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours
Cohort 3: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose+ Second Dose)
HoursCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose+ Second Dose)9.501 ± 22.5
SecondaryCohort 3: Minimum Observed Concentration (Cmin) of Digoxin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Picograms per milliliter
Cohort 3: Minimum Observed Concentration (Cmin) of Digoxin in Plasma
Picograms per milliliterCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: Minimum Observed Concentration (Cmin) of Digoxin in Plasma44.127 (34.943 to 55.723)77.447 (60.937 to 98.430)
Statistical analysis
  • Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg vs Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg · Ratio of geometric ls mean: 1.755 · 90% CI 1.304 to 2.363
SecondaryCohort 3: T1/2 of Digoxin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Hours
Cohort 3: T1/2 of Digoxin in Plasma
HoursCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: T1/2 of Digoxin in Plasma39.367 (37.263 to 41.589)32.777 (30.975 to 34.683)
Statistical analysis
  • Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg vs Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg · Ratio of geometric ls mean: 0.833 · 90% CI 0.769 to 0.902
SecondaryCohort 3: Vz/F of Digoxin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Liters
Cohort 3: Vz/F of Digoxin in Plasma
LitersCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: Vz/F of Digoxin in Plasma923.75 (810.79 to 1052.46)688.49 (602.73 to 786.46)
Statistical analysis
  • Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg vs Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg · Ratio of geometric ls mean: 0.745 · 90% CI 0.653 to 0.850
SecondaryCohort 3: CL/F of Digoxin in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Liters per Hour
Cohort 3: CL/F of Digoxin in Plasma
Liters per HourCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: CL/F of Digoxin in Plasma16.26 (14.51 to 18.23)14.51 (12.91 to 16.31)
Statistical analysis
  • Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg vs Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg · Ratio of geometric ls mean: 0.892 · 90% CI 0.782 to 1.018
SecondaryCohort 3: Cmin of Midazolam in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Nanograms per milliliter
Cohort 3: Cmin of Midazolam in Plasma
Nanograms per milliliterCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: Cmin of Midazolam in Plasma0.192 (0.157 to 0.234)0.222 (0.181 to 0.273)
Statistical analysis
  • Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg vs Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg · Ratio of geometric ls mean: 1.157 · 90% CI 0.876 to 1.528
SecondaryCohort 3: T1/2 of Midazolam in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Hours
Cohort 3: T1/2 of Midazolam in Plasma
HoursCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: T1/2 of Midazolam in Plasma5.320 (4.702 to 6.018)6.075 (5.358 to 6.887)
Statistical analysis
  • Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg vs Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg · Ratio of geometric ls mean: 1.142 · 90% CI 1.016 to 1.283
SecondaryCohort 3: Vz/F of Midazolam in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Liters
Cohort 3: Vz/F of Midazolam in Plasma
LitersCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: Vz/F of Midazolam in Plasma615.36 (537.88 to 704.01)371.24 (323.51 to 426.01)
Statistical analysis
  • Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg vs Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg · Ratio of geometric ls mean: 0.603 · 90% CI 0.521 to 0.699
SecondaryCohort 3: CL/F of Midazolam in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric least squares mean · Liters per Hour
Cohort 3: CL/F of Midazolam in Plasma
Liters per HourCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: CL/F of Midazolam in Plasma80.17 (67.66 to 94.99)42.16 (35.47 to 50.10)
Statistical analysis
  • Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg vs Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg · Ratio of geometric ls mean: 0.526 · 90% CI 0.448 to 0.618
SecondaryCohort 3: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose )

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Milligrams
Cohort 3: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose )
MilligramsCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose )1066.21 ± 40.4
SecondaryCohort 3: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose)

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Milligrams
Cohort 3: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose)
MilligramsCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Ae (0-2), n=17NA ± NA
Ae (2-4), n=18117.61 ± 101.7
Ae (4-6), n=16103.11 ± 57.3
Ae (6-8); n=1670.98 ± 53.7
Ae (8-12), n=1867.42 ± 44.3
Ae (12-14), n=1764.49 ± 94.1
Ae (14-16), n=15142.36 ± 142.3
Ae (16-18), n=14146.89 ± 59.4
Ae (18-20), n=1593.05 ± 83.5
Ae (20-24), n=1774.44 ± 93.9
Ae (24-36), n=1870.01 ± 105.0
Ae (36-48); n=1820.16 ± 46.4
Ae (48-60), n=188.51 ± 42.7
SecondaryCohort 3: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 3: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)
Hours*micrograms per milliliterCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)4770.8 ± 55.2
SecondaryCohort 3: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 3: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)
Hours*micrograms per milliliterCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)14333.9 ± 59.2
SecondaryCohort 3: AUC (0-48) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 3: AUC (0-48) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)
Hours*micrograms per milliliterCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: AUC (0-48) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)16682.1 ± 59.4
SecondaryCohort 3: Percentage of the Given Dose of Drug Excreted in Urine (fe%) Following Two 3000 mg Doses of Gepotidacin (First Dose + Second Dose )

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Percent dose excreted
Cohort 3: Percentage of the Given Dose of Drug Excreted in Urine (fe%) Following Two 3000 mg Doses of Gepotidacin (First Dose + Second Dose )
Percent dose excretedCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: Percentage of the Given Dose of Drug Excreted in Urine (fe%) Following Two 3000 mg Doses of Gepotidacin (First Dose + Second Dose )17.77 ± 40.4
SecondaryCohort 3: CLr of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose)

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Liters per Hour
Cohort 3: CLr of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose)
Liters per HourCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Cohort 3: CLr of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose)13.19 ± 34.6
SecondaryCohort 3: Number of Participants With SAE and Non-SAE

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.

Time frame:
Up to 30 days
Reported as:
Count of participants · Participants
Cohort 3: Number of Participants With SAE and Non-SAE
ParticipantsCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Any SAE00
Any non-SAE111
SecondaryCohort 3: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline

Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

Time frame:
Up to 30 days
Reported as:
Count of participants · Participants
Cohort 3: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
ParticipantsCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Basophils; To Low00
Basophils; To Normal or No Change1918
Basophils; To High00
Eosinophils; To Low00
Eosinophils; To Normal or No Change1916
Eosinophils; To High02
MCH; To Low00
MCH; To Normal or No Change1918
MCH; To High00
MCV; To Low00
MCV; To Normal or No Change1818
MCV; To High10
Erythrocytes; To Low21
Erythrocytes; To Normal or No Change1717
Erythrocytes; To High00
Hematocrit; To Low12
Hematocrit; To Normal or No Change1714
Hematocrit; To High12
Hemoglobin; To Low01
Hemoglobin; To Normal or No Change1815
Hemoglobin; To High12
Leukocytes; To Low00
Leukocytes; To Normal or No Change1917
Leukocytes; To High01
Lymphocytes; To Low00
Lymphocytes; To Normal or No Change1917
Lymphocytes; To High01
Monocytes; To Low01
Monocytes; To Normal or No Change1817
Monocytes; To High10
Neutrophils; To Low00
Neutrophils; To Normal or No Change1917
Neutrophils; To High01
Platelets; To Low00
Platelets; To Normal or No Change1918
Platelets; To High00
SecondaryCohort 3: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline

Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

Time frame:
Up to 30 days
Reported as:
Count of participants · Participants
Cohort 3: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
ParticipantsCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
ALT; To Low00
ALT; To Normal or No Change1917
ALT; To High01
Albumin; To Low10
Albumin; To Normal or No Change1817
Albumin; To High01
Alk Phos; To Low00
Alk Phos; To Normal or No Change1918
Alk Phos; To High00
AST; To Low00
AST; To Normal or No Change1818
AST; To High10
Bilirubin; To Low00
Bilirubin; To Normal or No Change1918
Bilirubin; To High00
Calcium; To Low11
Calcium; To Normal or No Change1817
Calcium; To High00
Carbon Dioxide; To Low00
Carbon Dioxide; To Normal or No Change1918
Carbon Dioxide; To High00
Chloride; To Low00
Chloride; To Normal or No Change1917
Chloride; To High01
Creatine Kinase; To Low00
Creatine Kinase; To Normal or No Change1818
Creatine Kinase; To High10
Creatinine; To Low00
Creatinine; To Normal or No Change1918
Creatinine; To High00
Direct Bilirubin; To Low00
Direct Bilirubin; To Normal or No Change1918
Direct Bilirubin; To High00
Glucose; To Low00
Glucose; To Normal or No Change1918
Glucose; To High00
Magnesium; To Low00
Magnesium; To Normal or No Change1918
Magnesium; To High00
Potassium; To Low00
Potassium; To Normal or No Change1818
Potassium; To High10
Protein; To Low00
Protein; To Normal or No Change1918
Protein; To High00
Sodium; To Low00
Sodium; To Normal or No Change1918
Sodium; To High00
BUN; To Low01
BUN; To Normal or No Change1917
BUN; To High00
SecondaryCohort 3: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline

Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

Time frame:
Up to 30 days
Reported as:
Count of participants · Participants
Cohort 3: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
ParticipantsCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
Bilirubin; To Normal or No Change1918
Bilirubin; To Abnormal00
Glucose; To Normal or No Change1918
Glucose; To Abnormal00
Ketones; To Normal or No Change1617
Ketones; To Abnormal31
Leukocyte Esterase; To Normal or No Change1313
Leukocyte Esterase; To Abnormal65
Nitrite; To Normal or No Change1918
Nitrite; To Abnormal00
Occult Blood; To Normal or No Change1413
Occult Blood; To Abnormal55
Protein; To Normal or No Change1616
Protein; To Abnormal32
pH; To Low00
pH; To Normal or No Change1918
pH; To High00
Specific Gravity; To Low00
Specific Gravity; To Normal or No Chan1610
Specific Gravity; To High38
SecondaryCohort 3: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline

Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.

Time frame:
Up to 30 days
Reported as:
Count of participants · Participants
Cohort 3: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
ParticipantsCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
DBP; To Low00
DBP; To Normal or No Change1918
DBP; To High00
SBP; To Low00
SBP; To Normal or No Change1918
SBP; To High00
Pulse rate; To Low00
Pulse rate; To Normal or No Change1918
Pulse rate; To High00
SecondaryCohort 3: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval

A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of \>450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported.

Time frame:
Up to 30 days
Reported as:
Count of participants · Participants
Cohort 3: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval
ParticipantsCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg
QTcB Interval25
QTcF Interval00
SecondaryCohort 4: T1/2 of Gepotidacin Following Single Dose of 1500 mg in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours
Cohort 4: T1/2 of Gepotidacin Following Single Dose of 1500 mg in Plasma
HoursCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg Fasted
Cohort 4: T1/2 of Gepotidacin Following Single Dose of 1500 mg in Plasma12.848 ± 28.512.540 ± 14.2
SecondaryCohort 4: Vz/F of Gepotidacin Following Single Dose of 1500 mg in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Liters
Cohort 4: Vz/F of Gepotidacin Following Single Dose of 1500 mg in Plasma
LitersCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg Fasted
Cohort 4: Vz/F of Gepotidacin Following Single Dose of 1500 mg in Plasma1246.70 ± 38.81329.83 ± 17.7
SecondaryCohort 4: CL/F of Gepotidacin Following Single Dose of 1500 mg in Plasma

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Liters per Hour
Cohort 4: CL/F of Gepotidacin Following Single Dose of 1500 mg in Plasma
Liters per HourCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg Fasted
Cohort 4: CL/F of Gepotidacin Following Single Dose of 1500 mg in Plasma67.26 ± 15.573.50 ± 13.3
SecondaryCohort 4: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Reported as:
Median · Hours
Cohort 4: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)-Fed State
HoursCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)-Fed State0 (0 to 0)
SecondaryCohort 4: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Reported as:
Geometric mean · Liters
Cohort 4: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
LitersCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State1251.05 ± 34.5
SecondaryCohort 4: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Reported as:
Geometric mean · Liters per Hour
Cohort 4: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
Liters per HourCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State68.83 ± 13.9
SecondaryCohort 4: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose )-Fed State

Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3
Reported as:
Geometric mean · Hours
Cohort 4: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose )-Fed State
HoursCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose )-Fed State12.599 ± 36.6
SecondaryCohort 4: Ae Total of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Milligrams
Cohort 4: Ae Total of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
MilligramsCohort 4: Gepotidacin 1500 mg Fed
Cohort 4: Ae Total of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine293.50 ± 29.0
SecondaryCohort 4: Ae(t1-t2) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Milligrams
Cohort 4: Ae(t1-t2) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
MilligramsCohort 4: Gepotidacin 1500 mg Fed
Ae (0-2)NA ± NA
Ae (2-4)102.23 ± 25.2
Ae (4-6)60.05 ± 57.0
Ae (6-8)31.61 ± 48.9
Ae (8-12)16.51 ± 97.0
Ae (12-24)17.16 ± 49.3
Ae (24-36)5.72 ± 196.5
Ae (36-48)4.28 ± 63.2
SecondaryCohort 4: AUC(0-24) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 4: AUC(0-24) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
Hours*micrograms per milliliterCohort 4: Gepotidacin 1500 mg Fed
Cohort 4: AUC(0-24) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine2142.4 ± 53.5
SecondaryCohort 4: AUC(0-48) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 4: AUC(0-48) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
Hours*micrograms per milliliterCohort 4: Gepotidacin 1500 mg Fed
Cohort 4: AUC(0-48) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine2293.7 ± 53.2
SecondaryCohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) for Gepotidacin 1500 mg Under Fed Condition

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100%.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Percent dose excreted
Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) for Gepotidacin 1500 mg Under Fed Condition
Percent dose excretedCohort 4: Gepotidacin 1500 mg Fed
Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) for Gepotidacin 1500 mg Under Fed Condition19.57 ± 29.0
SecondaryCohort 4: CLr of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Liters per Hour
Cohort 4: CLr of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition
Liters per HourCohort 4: Gepotidacin 1500 mg Fed
Cohort 4: CLr of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition13.42 ± 31.9
SecondaryCohort 4: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3
Reported as:
Geometric mean · Milligrams
Cohort 4: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
MilligramsCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State1334.42 ± 25.4
SecondaryCohort 4: Ae(t1-t2) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3
Reported as:
Geometric mean · Milligrams
Cohort 4: Ae(t1-t2) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
MilligramsCohort 4: Gepotidacin 3000 mg Fed
Ae (0-2); n=11NA ± NA
Ae (2-4); n=10221.19 ± 56.7
Ae (4-6); n=11103.68 ± 70.6
Ae (6-8); n=1167.58 ± 49.5
Ae (8-12); n=1165.06 ± 22.7
Ae (12-14); n=11112.83 ± 66.3
Ae (14-16); n=11174.62 ± 85.2
Ae (16-18); n=11136.66 ± 68.1
Ae (18-20); n=1190.81 ± 25.4
Ae (20-24); n=1180.54 ± 20.4
Ae (24-36); n=1157.62 ± 42.9
Ae (36-48); n=1114.47 ± 36.9
Ae (48-60); n=109.67 ± 61.7
SecondaryCohort 4: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 4: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
Hours*micrograms per milliliterCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State4996.9 ± 64.4
SecondaryCohort 4: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours post-dose in Treatment Period 3
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 4: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
Hours*micrograms per milliliterCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State14729.5 ± 59.3
SecondaryCohort 4: AUC(0-48) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours post-dose in Treatment Period 3
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 4: AUC(0-48) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
Hours*micrograms per milliliterCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: AUC(0-48) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State15768.2 ± 58.8
SecondaryCohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin Following Two 3000 mg Doses-Fed State

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3
Reported as:
Geometric mean · Percent dose excreted
Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin Following Two 3000 mg Doses-Fed State
Percent dose excretedCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin Following Two 3000 mg Doses-Fed State22.24 ± 25.4
SecondaryCohort 4: CLr of Gepotidacin Following Two 3000 mg Dose-Fed State

Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3
Reported as:
Geometric mean · Liters per Hour
Cohort 4: CLr of Gepotidacin Following Two 3000 mg Dose-Fed State
Liters per HourCohort 4: Gepotidacin 3000 mg Fed
Cohort 4: CLr of Gepotidacin Following Two 3000 mg Dose-Fed State14.61 ± 19.3
Other pre-specifiedCohort 4: AUC(0-tau) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine

Urine samples were collected at indicated time points. AUC(0-tau) can be calculated only for multiple doses and not for single dose as tau refers to the dosing interval. Hence, AUC(0-tau) could not be calculated for Gepotidacin 1500 mg single dose as mentioned in Reporting and Analysis Plan. The results for this outcome measure will never be posted.

Time frame:
Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2
Reported as:
Geometric mean · Hours*micrograms per milliliter
Cohort 4: AUC(0-tau) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
Hours*micrograms per milliliterCohort 4: Gepotidacin 1500 mg Fed
Cohort 4: AUC(0-tau) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in UrineNA ± NA

Adverse events

Collected over Serious adverse events (SAE) and non-serious adverse events (non-SAE) were collected up to 17 days during Cohort 1; up to 26 days during Cohort 2; up to 30 days during Cohort 3 and up to 22 days during Cohort 4.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cohort 1: Gepotidacin 1500 mg0/14 (0%)0/14 (0%)0/14 (0%)
Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg0/13 (0%)0/13 (0%)0/13 (0%)
Cohort 2: Period 1: Gepotidacin 1500 mg0/17 (0%)0/17 (0%)3/17 (17.6%)
Cohort 2: Period 2 (Days 1 to 7) Rifampicin 600 mg0/17 (0%)0/17 (0%)2/17 (11.8%)
Cohort 2: Period 2 (Days 8 to 9) Gepotidacin 1500 mg + Rifampicin 600 mg0/14 (0%)0/14 (0%)2/14 (14.3%)
Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg0/19 (0%)0/19 (0%)1/19 (5.3%)
Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg0/18 (0%)0/18 (0%)11/18 (61.1%)
Cohort 4: Placebo0/3 (0%)0/3 (0%)0/3 (0%)
Cohort 4: Gepotidacin 1500 mg Fed0/11 (0%)0/11 (0%)1/11 (9.1%)
Cohort 4: Gepotidacin 1500 mg Fasted0/11 (0%)0/11 (0%)2/11 (18.2%)
Cohort 4: Gepotidacin 3000 mg Fed0/11 (0%)0/11 (0%)4/11 (36.4%)
Most frequent other events
Most frequent other events
EventCohort 1: Gepotidacin 1500 mgCohort 1: Gepotidacin 1500 mg + Cimetidine 400 mgCohort 2: Period 1: Gepotidacin 1500 mgCohort 2: Period 2 (Days 1 to 7) Rifampicin 600 mgCohort 2: Period 2 (Days 8 to 9) Gepotidacin 1500 mg + Rifampicin 600 mgCohort 3: Digoxin 0.5 mg + Midazolam 2 mgCohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mgCohort 4: PlaceboCohort 4: Gepotidacin 1500 mg FedCohort 4: Gepotidacin 1500 mg FastedCohort 4: Gepotidacin 3000 mg Fed
DiarrhoeaGastrointestinal disorders0/140/132/170/172/140/196/180/30/110/113/11
NauseaGastrointestinal disorders0/140/131/172/170/140/194/180/31/112/112/11
HeadacheNervous system disorders0/140/132/171/170/140/190/180/30/110/110/11
Electrocardiogram T wave abnormalInvestigations0/140/130/170/170/141/192/180/30/110/110/11

Baseline characteristics

Age, Customized
Age, Customized(Participants)Cohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo FedTotal
<18 years00000000
18-64 years141710965364
>=65 years00000000
Sex: Female, Male
Sex: Female, Male(Participants)Cohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo FedTotal
Female743522225
Male7137443139
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Cohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mgCohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + RifampicinCohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + MidazolamCohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+MidazolamCohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg FedCohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg FedCohort 4: Placebo Fed/ Placebo Fasted/ Placebo FedTotal
BLACK OR AFRICAN AMERICAN876500026
NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER11000002
WHITE454400017
BLACK OR AFRICAN AMERICAN/WHITE10000001
ASIAN(A)/BLACK OR AFRICAN AMERICAN01000001
JAPANESE HERITAGE(H)/EAST A H/SOUTH EAST A H020065316
AMERICAN INDIAN OR ALASKA NATIVE/WHITE01000001
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Study locations

1 site
  • GSK Investigational Site
    Las Vegas, Nevada 89113, United States
09

References and documents

Study documents

  • Study protocol · Jul 13, 2020
  • Statistical analysis plan · Dec 16, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — IPD for this study will be made available via the Clinical Study Data Request site.

Supporting information: Study protocol, Sap, Icf, Csr

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 4, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04493931
Lead sponsor
GlaxoSmithKline
Responsible party
Sponsor
First posted
Jul 30, 2020
Start date
Aug 14, 2020
Primary completion
Dec 21, 2020
Completion
Dec 21, 2020
Results posted
Mar 4, 2022
Last update
Mar 4, 2022

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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