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CompletedNCT03568942Updated Jun 29, 2020Results posted

Pharmacokinetic Study of Oral Gepotidacin (GSK2140944) in Subjects With Uncomplicated Urinary Tract Infection (Acute Cystitis)

A Phase 2 interventional study of Gepotidacin in Infections, Bacterial, sponsored by GlaxoSmithKline. Completed at 1 site in United States. Open to female participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2020-06-29.

Sponsored by GlaxoSmithKline · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
22
Allocation
Not applicable
Ages
18 Years to 65 Years
Sex
Female
01

Study summary

Gepotidacin (GSK2140944) is a novel triazaacenaphthylene bacterial type II topoisomerase inhibitor that is being developed for the treatment of uncomplicated urinary tract infections (UTIs; acute cystitis). This Phase IIa study will evaluate plasma and urine pharmacokinetics of gepotidacin in female subjects with acute cystitis. Eligible female subjects will receive twice daily (BID) dose of gepotidacin 1500 milligram (mg) for 5 days via oral route. Pre-treatment and post-treatment samples for pharmacokinetic (PK) assessments will be collected throughout the study. The total duration of the study is approximately 28 days.

02

Conditions studied

  • Infections, Bacterial

Keywords

  • gepotidacin
  • GSK2140944
  • acute cystitis
  • pharmacokinetics
  • urinary tract infections
03

In context

Bacterial Infections

665 studies on the registry are indexed under Bacterial Infections; 99 are open to participants now.

This study's enrollment of 22 is below the median of 80 across 410 interventional studies indexed under Bacterial Infections.

Browse Bacterial Infections studies →

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,647 studies on the registry; 118 are open to participants now.

Of its 264 completed or terminated interventional studies of FDA-regulated products, 239 (91%) have results posted.

Browse GlaxoSmithKline studies →

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

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
Female
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Subject must be >=18 to \<=65 years of age inclusive, at the time of signing the informed consent.
  • The subject has 2 or more of the following clinical signs and symptoms of acute cystitis with onset \<=72 hours of the screening assessment: dysuria, frequency, urgency, or lower abdominal pain.
  • The subject has pyuria (>=10 white blood cells per cubic millimeters [WBC/mm\^3] or the presence of leukocyte esterase) and/or nitrite from a pretreatment clean-catch midstream urine sample based on local laboratory procedures.
  • The subject is female. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: a) Not a woman of childbearing potential (WOCBP) OR b) A WOCBP who agrees to follow the contraceptive guidance from the Baseline Visit through completion of the Test of Cure (TOC) Visit.
  • Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.

Exclusion criteria

Exclusion Criteria:

  • The subject resides in a nursing home or dependent care-type facility.
  • The subject has a body mass index >=40.0 kilogram per square meter (kg/m\^2) or a body mass index >=35.0 kg/m\^2 with obesity-related health conditions such as high blood pressure or uncontrolled diabetes.
  • The subject has a history of sensitivity to the study treatment, or components thereof, or a history of a drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates her participation.
  • The subject is immunocompromised or has altered immune defenses that may predispose the subject to a higher risk of treatment failure and/or complications (e.g., renal transplant recipients, subjects with clinically significant persistent granulocytopenia [absolute neutrophil count \<1000/microliter (µL)], and subjects receiving immunosuppressive therapy, including corticosteroid therapy [>40 mg/day prednisolone or equivalent for >1 week or >=20 milligrams per day (mg/day) prednisolone or equivalent for >6 weeks; or prednisolone or equivalent >=10 mg/day for >6 weeks]). Subjects with a known cluster of differentiation 4 (CD4) count of \<200 cells/mm\^3 should not be enrolled.
  • The subject has uncontrolled diabetes, defined as a non-fasting glucose value >300 milligrams per deciliter (mg/dL) or based on investigator judgment.
  • The subject has any of the following: A medical condition that requires medication that may be aggravated by inhibition of acetylcholinesterase, such as: a) Poorly controlled asthma or chronic obstructive pulmonary disease at Baseline and, in the opinion of the investigator, not stable on current therapy; b) Acute severe pain, uncontrolled with conventional medical management; c) Active peptic ulcer disease; d) Parkinson disease; e) Myasthenia gravis; f) A history of seizure disorder requiring medications for control (this does not include a history of childhood febrile seizures) OR Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study drug (e.g., ileostomy or malabsorption syndrome). Subjects who have had a gastric bypass or a cholecystectomy are excluded from the study OR Hemoglobin value \<12 grams per deciliter (g/dL) or a known uncorrected iron deficiency.
  • The subject, in the judgment of the investigator, would not be able or willing to comply with the protocol or complete study follow-up.
  • The subject has a serious underlying disease that could be imminently life threatening, or the subject is unlikely to survive for the duration of the study period.
  • The subject has acute cystitis that is known or suspected to be due to fungal, parasitic, or viral pathogens; or known or suspected to be due to Pseudomonas aeruginosa or Enterobacteriaceae (other than Escherichia coli [E. coli]) as the contributing pathogen.
  • The subject has symptoms known or suspected to be caused by another disease process such as asymptomatic bacteriuria or chronic interstitial cystitis.
  • The subject has an anatomical or physiological anomaly that predisposes the subject to UTIs or may be a source of persistent bacterial colonization, including calculi, obstruction or stricture of the urinary tract, primary renal disease (e.g., polycystic renal disease), or neurogenic bladder, or the subject has a history of anatomical or functional abnormalities of the urinary tract (e.g., chronic vesico-ureteral reflux, detrusor insufficiency).
  • The subject has an indwelling catheter, nephrostomy, ureter stent, or other foreign material in the urinary tract.
  • The subject who, in the opinion of the investigator, has an otherwise complicated UTI, an active upper UTI (e.g., pyelonephritis, urosepsis), signs and symptoms onset >=96 hours before the Screening assessment, or a temperature >=101 degree Fahrenheit, flank pain, chills, or any other manifestations suggestive of upper UTI.
  • The subject has anuria, oliguria, or significant impairment of renal function (creatinine clearance \<30 milliliters per minute [mL/min] or clinically significant elevated serum creatinine).
  • The subject presents with vaginal discharge at Baseline (e.g., suspected sexually transmitted disease).
  • The subject has congenital long QT syndrome or known prolongation of the corrected QT (QTc) interval.
  • The subject has uncompensated heart failure, defined as New York Heart Association Class >=III.
  • The subject has severe left ventricular hypertrophy.
  • The subject has a family history of QT prolongation or sudden death.
  • The subject has a recent history of vasovagal syncope or episodes of symptomatic bradycardia or bradyarrhythmia within the last 12 months.
  • The subject is taking QT-prolonging drugs or drugs known to increase the risk of torsades de points (TdP) per the www.crediblemeds.org "Known Risk of TdP" category at the time of her Baseline Visit, which cannot be safely discontinued from the Baseline Visit to the TOC Visit; or the subject is taking a strong cytochrome P450 enzyme 3A4 (CYP3A4) inhibitor or a strong P-glycoprotein (P-gp) inhibitor.
  • The subject has a QT interval corrected for heart rate (QTc) >450 milliseconds (msec) or a QTc >480 msec for subjects with bundle-branch block.
  • The subject has a known ALT value >2 times upper limit of normal (ULN).
  • The subject has a known bilirubin value >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
  • The subject has a current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones), including symptomatic viral hepatitis or moderate-to-severe liver insufficiency (Child Pugh class B or C).
  • The subject has received treatment with other systemic antimicrobials or systemic antifungals within 1 week before study entry.
  • The subject must agree not to use the medications or nondrug therapies from the Baseline Visit through the TOC Visit.
  • The subject has been previously enrolled in this study or has previously been treated with gepotidacin.
  • The subject has participated in a clinical trial and has received an investigational product within 30 days or 5 half-lives, whichever is longer.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
22 participants (actual)

Study arms

  • Experimental
    Female subjects with acute cystitis

    Adult female subjects with suspected acute cystitis based on clinical presentation and pyuria (\>=10 WBC/mm\^3 or presence of leukocyte esterase) and/or nitrite will be included. Subjects will be administered 1500 mg gepotidacin BID for 5 days via the oral route.

    Drug: Gepotidacin

Interventions

  • DrugGepotidacin

    Gepotidacin tablets will be available at a dose strength of 750 mg. Tablets will be administered BID with water after consumption of food.

06

What researchers measure

Primary outcomes

  1. Area Under the Plasma Concentration-time Curve (AUC) From Zero (Pre-dose) Over the Dosing Interval (AUC[0-tau]) of Gepotidacin

    Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. PK Parameter Population consisted of all participants who received gepotidacin 1500 mg BID through the completion of all PK collections for whom valid and evaluable plasma PK parameters were derived for gepotidacin.

    Time frame: Days 1 and 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose

  2. Maximum Plasma Concentration (Cmax) of Gepotidacin

    Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.

    Time frame: Days 1 and 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose

  3. Time of Occurrence of Cmax (Tmax) of Gepotidacin

    Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.

    Time frame: Days 1 and 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose

  4. Apparent Steady State Clearance (CLss/F) of Gepotidacin

    Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. CLss/F was calculated as Dose divided by AUC(0-tau).

    Time frame: Day 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose

  5. Accumulation Ratio (Ro) of Gepotidacin

    Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. Accumulation ratio (Ro) was calculated as ratio of AUC(0-tau) at Day 4 to AUC(0-tau) at Day 1.

    Time frame: Days 1 and 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose

  6. Plasma Pre-dose Concentration (Ctau) of Gepotidacin

    Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.

    Time frame: Days 1 to 5: Pre-dose

Secondary outcomes

  1. Amount of Drug Excreted Over 12 Hours (Ae12hours) of Gepotidacin

    Urine samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. Ae12hours was calculated by adding all the fractions of drug collected over all the allotted time intervals.

    Time frame: Days 1 and 4: Pre-dose and at 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 10 hours, and 10 to 12 hours post-dose

  2. Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin

    Ae(t1-t2) measure the amount of drug excreted in urine in a time intervals 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 10 hours, and 10 to 12 hours post-dose on Days 1 and 4. The PK parameters were calculated by standard non-compartmental analysis.

    Time frame: Days 1 and 4: Pre-dose and at 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 10 hours, and 10 to 12 hours post-dose

  3. Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin

    Urine samples were collected to evaluate the PK of gepotidacin at the indicated time points. fe% was calculated as fe% = (Ae 12 hours/Dose) multiply by 100. The PK parameters were calculated by standard non-compartmental analysis.

    Time frame: Days 1 and 4: Pre-dose and at 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 10 hours, and 10 to 12 hours post-dose

  4. Renal Clearance (CLr) of Gepotidacin

    Urine samples were collected to evaluate the PK of gepotidacin at the indicated time points. CLr was calculated as CLr = Ae 12 hours/AUC(0-tau). The PK parameters were calculated by standard non-compartmental analysis.

    Time frame: Days 1 and 4: Pre-dose and at 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 10 hours, and 10 to 12 hours post-dose

  5. Urine Pre-dose Concentration (Ctau) of Gepotidacin

    Urine samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.

    Time frame: Days 1 to 5: Pre-dose

  6. Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious AEs (SAEs)

    An AEs is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; and other important medical events which may require medical or surgical intervention. Safety Population consisted of all participants who received at least 1 dose of gepotidacin.

    Time frame: Up to Day 31

  7. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

    Vital signs including SBP and DBP were measured in semi-supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was defined as the latest non-missing value at Day -1 or at Day 1 pre-dose. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

    Time frame: Baseline, Day 2, Day 3, Day 4, Day 5 and Days 10 to 13 (Test-of-cure visit)

  8. Change From Baseline in Pulse Rate

    Vital sign including pulse rate was measured in semi-supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was defined as the latest non-missing value at Day -1 or at Day 1 pre-dose. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

    Time frame: Baseline, Day 2, Day 3, Day 4, Day 5 and Days 10 to 13 (Test-of-cure visit)

  9. Change From Baseline in Body Temperature

    Vital sign including body temperature was measured in semi-supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was defined as the latest non-missing value at Day -1 or at Day 1 pre-dose. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

    Time frame: Baseline, Day 2, Day 3, Day 4, Day 5 and Days 10 to 13 (Test-of-cure visit)

  10. Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Bazett's Formula (QTcB) and Corrected QT Interval Using Fridericia's Formula (QTcF)

    A 12-lead ECG was measured in semi-supine position using an ECG machine that measured PR interval, QRS duration, QT interval, QTcB and QTcF. Baseline was defined as the latest non-missing value at Day -1 or at Day 1 pre-dose. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

    Time frame: Baseline; Day 1: 2 hours; Day 4: pre-dose and 2 hours

  11. Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet Counts

    Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet counts. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

    Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)

  12. Change From Baseline in Hematology Parameter: Hemoglobin

    Blood samples were collected to analyze the hematology parameter: Hemoglobin. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

    Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)

  13. Change From Baseline in Hematology Parameter: Hematocrit

    Blood samples were collected to analyze the hematology parameter: Hematocrit. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

    Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)

  14. Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Hemoglobin

    Blood samples were collected to analyze the hematology parameter: Erythrocyte Mean Corpuscular Hemoglobin. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

    Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)

  15. Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Volume

    Blood samples were collected to analyze the hematology parameter: Erythrocyte Mean Corpuscular Volume. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

    Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)

  16. Change From Baseline in Hematology Parameter: Red Blood Cell Count

    Blood samples were collected to analyze the hematology parameter: Red blood cell count. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

    Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)

  17. Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein

    Blood samples were collected to analyze the chemistry parameters: Albumin and Protein. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

    Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)

  18. Change From Baseline in Clinical Chemistry Parameters: Creatinine and Bilirubin

    Blood samples were collected to analyze the chemistry parameters: Creatinine and Bilirubin. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

    Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)

  19. Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (ALP)

    Blood samples were collected to analyze the chemistry parameters: ALT, AST and ALP. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

    Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)

  20. Change From Baseline in Clinical Chemistry Parameters: Glucose, Calcium, Chloride, Potassium, Sodium and Urea

    Blood samples were collected to analyze the chemistry parameters: Glucose, Calcium, Chloride, Potassium, Sodium and Urea. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

    Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)

  21. Number of Participants With Urinalysis Dipstick Results: Glucose and Nitrites

    Urine samples were collected at indicated time points to analyze parameters including glucose and nitrites by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative and positive in the urine sample. Baseline was defined as Day -1. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13. Only categories with significant values have been presented.

    Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)

  22. Number of Participants With Urinalysis Dipstick Results: Ketones

    Urine samples were collected at indicated time points to analyze parameter including ketones by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative, 5 indicates 5 milligrams per deciliter (mg/dL) and 20 indicates 20 mg/dL in the urine sample. Baseline was defined as Day -1. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13. Only categories with significant values have been presented.

    Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)

  23. Number of Participants With Urinalysis Dipstick Results: Leukocyte Esterase

    Urine samples were collected at indicated time points to analyze parameter including leukocyte esterase by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative, Trace indicates 15 Leukocytes per microliter (Leuko/mcL), Small indicates 70 Leuko/mcL, Moderate indicates 125 Leuko/mcL and Large indicates 500 Leuko/mcL in the urine sample. Baseline was defined as Day -1. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13. Only categories with significant values have been presented.

    Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)

  24. Number of Participants With Urinalysis Dipstick Results: Occult Blood

    Urine samples were collected at indicated time points to analyze parameter including occult blood by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative, Small indicates 25 Erythrocytes per microliter (Ery/mcL), Moderate indicates 50 Ery/mcL and Large indicates 250 Ery/mcL in the urine sample. Baseline was defined as Day -1. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13. Only categories with significant values have been presented.

    Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)

  25. Number of Participants With Urinalysis Dipstick Results: Protein

    Urine samples were collected at indicated time points to analyze parameter including protein by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative indicates \<10 mg/dL, 1+ indicates 30 mg/dL and 2+ indicates 100 mg/dL in the urine sample. Baseline was defined as Day -1. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13. Only categories with significant values have been presented.

    Time frame: Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)

  26. Number of Participants With Abnormal Physical Examination Findings

    Physical examinations included assessments of the respiratory, cardiovascular, abdominal, gastrointestinal, neurological and urogenital systems. This analysis was planned but data was not collected and captured in the database.

    Time frame: Up to Day 31

07

Results

Posted Jan 7, 2020

Participant flow

This was an open-label study to evaluate the pharmacokinetic (PK) of repeat oral doses of gepotidacin in adult female participants with clinical signs and symptoms of acute cystitis.

Participant flow — Overall Study
MilestoneGepotidacin 1500 mg
Started22
Completed20
Not completed2
Withdrew: Family emergency1
Withdrew: Lost to follow-up1

Outcome measures

PrimaryArea Under the Plasma Concentration-time Curve (AUC) From Zero (Pre-dose) Over the Dosing Interval (AUC[0-tau]) of Gepotidacin

Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. PK Parameter Population consisted of all participants who received gepotidacin 1500 mg BID through the completion of all PK collections for whom valid and evaluable plasma PK parameters were derived for gepotidacin.

Time frame:
Days 1 and 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
Reported as:
Geometric mean · Hours* nanogram per milliliter (h*ng/mL)
Area Under the Plasma Concentration-time Curve (AUC) From Zero (Pre-dose) Over the Dosing Interval (AUC[0-tau]) of Gepotidacin
Hours* nanogram per milliliter (h*ng/mL)Gepotidacin 1500 mg
Day 1, n=2020236.2 ± 28.6
Day 4, n=2129313.8 ± 31.8
PrimaryMaximum Plasma Concentration (Cmax) of Gepotidacin

Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.

Time frame:
Days 1 and 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
Reported as:
Geometric mean · Nanogram per milliliter (ng/mL)
Maximum Plasma Concentration (Cmax) of Gepotidacin
Nanogram per milliliter (ng/mL)Gepotidacin 1500 mg
Day 1, n=205891 ± 47.3
Day 4, n=218437 ± 38.0
PrimaryTime of Occurrence of Cmax (Tmax) of Gepotidacin

Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.

Time frame:
Days 1 and 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
Reported as:
Median · Hours
Time of Occurrence of Cmax (Tmax) of Gepotidacin
HoursGepotidacin 1500 mg
Day 1, n=201.500 (0.47 to 3.07)
Day 4, n=211.917 (0.45 to 4.12)
PrimaryApparent Steady State Clearance (CLss/F) of Gepotidacin

Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. CLss/F was calculated as Dose divided by AUC(0-tau).

Time frame:
Day 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
Reported as:
Geometric mean · Liters per hour
Apparent Steady State Clearance (CLss/F) of Gepotidacin
Liters per hourGepotidacin 1500 mg
Apparent Steady State Clearance (CLss/F) of Gepotidacin51.17 ± 31.8
PrimaryAccumulation Ratio (Ro) of Gepotidacin

Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. Accumulation ratio (Ro) was calculated as ratio of AUC(0-tau) at Day 4 to AUC(0-tau) at Day 1.

Time frame:
Days 1 and 4: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 12 hours post-dose
Reported as:
Geometric mean · Ratio
Accumulation Ratio (Ro) of Gepotidacin
RatioGepotidacin 1500 mg
Accumulation Ratio (Ro) of Gepotidacin1.402 ± 20.4
PrimaryPlasma Pre-dose Concentration (Ctau) of Gepotidacin

Blood samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.

Time frame:
Days 1 to 5: Pre-dose
Reported as:
Geometric mean · ng/mL
Plasma Pre-dose Concentration (Ctau) of Gepotidacin
ng/mLGepotidacin 1500 mg
Day 1, Pre-dose, n=22NA ± NA
Day 2, Pre-dose, n=21620.5 ± 62.3
Day 3, Pre-dose, n=21789.3 ± 37.4
Day 4, Pre-dose, n=21851.4 ± 41.4
Day 5, Pre-dose, n=21818.9 ± 46.4
SecondaryAmount of Drug Excreted Over 12 Hours (Ae12hours) of Gepotidacin

Urine samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis. Ae12hours was calculated by adding all the fractions of drug collected over all the allotted time intervals.

Time frame:
Days 1 and 4: Pre-dose and at 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 10 hours, and 10 to 12 hours post-dose
Reported as:
Geometric mean · mg
Amount of Drug Excreted Over 12 Hours (Ae12hours) of Gepotidacin
mgGepotidacin 1500 mg
Day 1, n=20298.7 ± 107.6
Day 4, n=21460.0 ± 55.8
SecondaryAmount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin

Ae(t1-t2) measure the amount of drug excreted in urine in a time intervals 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 10 hours, and 10 to 12 hours post-dose on Days 1 and 4. The PK parameters were calculated by standard non-compartmental analysis.

Time frame:
Days 1 and 4: Pre-dose and at 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 10 hours, and 10 to 12 hours post-dose
Reported as:
Geometric mean · mg
Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin
mgGepotidacin 1500 mg
Day 1, Ae (0-2),n=17NA ± NA
Day 4, Ae (0-2),n=1863.05 ± 151.7
Day 1, Ae (2-4),n=17131.9 ± 59.5
Day 4, Ae (2-4),n=12168.1 ± 96.5
Day 1, Ae (4-6) ,n=1487.01 ± 90.0
Day 4, Ae (4-6),n=18128.6 ± 96.8
Day 1, Ae (6-8),n=1654.60 ± 72.1
Day 4, Ae (6-8),n=1784.08 ± 92.0
Day 1, Ae (8-10),n=918.51 ± 49.9
Day 4, Ae (8-10),n=1034.68 ± 69.2
Day 1, Ae (10-12),n=1418.03 ± 151.2
Day 4, Ae (10-12),n=1532.77 ± 83.5
SecondaryPercentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin

Urine samples were collected to evaluate the PK of gepotidacin at the indicated time points. fe% was calculated as fe% = (Ae 12 hours/Dose) multiply by 100. The PK parameters were calculated by standard non-compartmental analysis.

Time frame:
Days 1 and 4: Pre-dose and at 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 10 hours, and 10 to 12 hours post-dose
Reported as:
Geometric mean · Percentage of dose
Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin
Percentage of doseGepotidacin 1500 mg
Day 1, n=2019.91 ± 107.6
Day 4, n=2130.67 ± 55.8
SecondaryRenal Clearance (CLr) of Gepotidacin

Urine samples were collected to evaluate the PK of gepotidacin at the indicated time points. CLr was calculated as CLr = Ae 12 hours/AUC(0-tau). The PK parameters were calculated by standard non-compartmental analysis.

Time frame:
Days 1 and 4: Pre-dose and at 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 10 hours, and 10 to 12 hours post-dose
Reported as:
Geometric mean · Liters per hour
Renal Clearance (CLr) of Gepotidacin
Liters per hourGepotidacin 1500 mg
Day 1, n=2014.76 ± 118.2
Day 4, n=2115.69 ± 45.2
SecondaryUrine Pre-dose Concentration (Ctau) of Gepotidacin

Urine samples were collected to evaluate the PK of gepotidacin at the indicated time points. The PK parameters were calculated by standard non-compartmental analysis.

Time frame:
Days 1 to 5: Pre-dose
Reported as:
Geometric mean · Micrograms per milliliter
Urine Pre-dose Concentration (Ctau) of Gepotidacin
Micrograms per milliliterGepotidacin 1500 mg
Day 1, Pre-dose, n=21NA ± NA
Day 2, Pre-dose, n=20279.1 ± 154.7
Day 3, Pre-dose, n=21322.2 ± 138.8
Day 4, Pre-dose, n=21326.7 ± 248.7
Day 5, Pre-dose, n=21351.7 ± 146.5
SecondaryNumber of Participants With Non-serious Adverse Events (Non-SAEs) and Serious AEs (SAEs)

An AEs is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; and other important medical events which may require medical or surgical intervention. Safety Population consisted of all participants who received at least 1 dose of gepotidacin.

Time frame:
Up to Day 31
Reported as:
Count of participants · Participants
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious AEs (SAEs)
ParticipantsGepotidacin 1500 mg
Non-SAEs21
SAEs1
SecondaryChange From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Vital signs including SBP and DBP were measured in semi-supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was defined as the latest non-missing value at Day -1 or at Day 1 pre-dose. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

Time frame:
Baseline, Day 2, Day 3, Day 4, Day 5 and Days 10 to 13 (Test-of-cure visit)
Reported as:
Mean · Millimeters of mercury
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Millimeters of mercuryGepotidacin 1500 mg
SBP, Day 2,n=22-3.1 ± 16.13
SBP, Day 3,n=22-0.3 ± 15.74
SBP, Day 4,n=21-1.5 ± 13.10
SBP, Day 5,n=210.9 ± 15.46
SBP, Days 10 to 13,n=201.5 ± 14.21
DBP, Day 2,n=22-2.3 ± 9.32
DBP, Day 3,n=22-1.1 ± 11.64
DBP, Day 4,n=210.5 ± 9.65
DBP, Day 5,n=214.7 ± 7.23
DBP, Days 10 to 13,n=202.7 ± 8.77
SecondaryChange From Baseline in Pulse Rate

Vital sign including pulse rate was measured in semi-supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was defined as the latest non-missing value at Day -1 or at Day 1 pre-dose. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

Time frame:
Baseline, Day 2, Day 3, Day 4, Day 5 and Days 10 to 13 (Test-of-cure visit)
Reported as:
Mean · Beats per minute
Change From Baseline in Pulse Rate
Beats per minuteGepotidacin 1500 mg
Day 2,n=222.2 ± 9.07
Day 3,n=222.4 ± 10.24
Day 4,n=212.9 ± 12.60
Day 5,n=217.2 ± 9.50
Days 10 to 13,n=200.8 ± 12.38
SecondaryChange From Baseline in Body Temperature

Vital sign including body temperature was measured in semi-supine position after 5 minutes of rest for the participants in a quiet setting without distractions. Baseline was defined as the latest non-missing value at Day -1 or at Day 1 pre-dose. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

Time frame:
Baseline, Day 2, Day 3, Day 4, Day 5 and Days 10 to 13 (Test-of-cure visit)
Reported as:
Mean · Degree Celsius
Change From Baseline in Body Temperature
Degree CelsiusGepotidacin 1500 mg
Day 2,n=22-0.05 ± 0.246
Day 3,n=22-0.06 ± 0.292
Day 4,n=210.02 ± 0.405
Day 5,n=21-0.05 ± 0.287
Days 10 to 13,n=20-0.10 ± 0.270
SecondaryChange From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Bazett's Formula (QTcB) and Corrected QT Interval Using Fridericia's Formula (QTcF)

A 12-lead ECG was measured in semi-supine position using an ECG machine that measured PR interval, QRS duration, QT interval, QTcB and QTcF. Baseline was defined as the latest non-missing value at Day -1 or at Day 1 pre-dose. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value.

Time frame:
Baseline; Day 1: 2 hours; Day 4: pre-dose and 2 hours
Reported as:
Mean · Millisecond
Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Bazett's Formula (QTcB) and Corrected QT Interval Using Fridericia's Formula (QTcF)
MillisecondGepotidacin 1500 mg
PR interval, Day 1: 2 hours, n=22-1.9 ± 11.34
PR interval, Day 4: pre-dose,n=210.1 ± 14.56
PR interval, Day 4: 2 hours,n=21-3.5 ± 10.17
QRS duration, Day 1: 2 hours, n=22-0.7 ± 8.32
QRS duration, Day 4: pre-dose,n=21-0.9 ± 4.10
QRS duration, Day 4: 2 hours,n=212.1 ± 4.29
QT interval, Day 1: 2 hours, n=2215.0 ± 21.56
QT interval, Day 4: pre-dose,n=21-5.4 ± 26.86
QT interval, Day 4: 2 hours,n=218.7 ± 27.46
QTcB interval, Day 1: 2 hours, n=224.5 ± 14.37
QTcB interval, Day 4: pre-dose,n=21-6.2 ± 17.25
QTcB interval, Day 4: 2 hours,n=210.4 ± 27.33
QTcF interval, Day 1: 2 hours, n=228.2 ± 14.45
QTcF interval, Day 4: pre-dose,n=21-5.8 ± 17.57
QTcF interval, Day 4: 2 hours,n=213.4 ± 24.84
SecondaryChange From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet Counts

Blood samples were collected to analyze the hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet counts. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

Time frame:
Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Reported as:
Mean · 10^9 cells per liter
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelet Counts
10^9 cells per literGepotidacin 1500 mg
Day 3, Basophils, n=160.013 ± 0.0652
Day 5, Basophils, n=14-0.003 ± 0.0164
Days 10 to 13, Basophils, n=150.000 ± 0.0146
Day 3, Eosinophils, n=180.013 ± 0.0550
Day 5, Eosinophils, n=17-0.003 ± 0.0969
Days 10 to 13, Eosinophils, n=160.051 ± 0.0492
Day 3, Lymphocytes, n=190.039 ± 0.5201
Day 5, Lymphocytes, n=180.041 ± 0.4856
Days 10 to 13, Lymphocytes, n=170.232 ± 0.4001
Day 3, Monocytes, n=19-0.053 ± 0.1080
Day 5, Monocytes, n=18-0.069 ± 0.1468
Days 10 to 13, Monocytes, n=17-0.039 ± 0.1415
Day 3, Neutrophils, n=19-0.673 ± 1.9611
Day 5, Neutrophils, n=18-0.948 ± 2.3174
Days 10 to 13, Neutrophils, n=17-0.841 ± 1.4779
Day 3, Platelet counts, n=19-3.6 ± 22.94
Day 5, Platelet counts, n=187.8 ± 32.33
Days 10 to 13, Platelet counts, n=173.7 ± 33.59
SecondaryChange From Baseline in Hematology Parameter: Hemoglobin

Blood samples were collected to analyze the hematology parameter: Hemoglobin. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

Time frame:
Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Reported as:
Mean · Grams per liter
Change From Baseline in Hematology Parameter: Hemoglobin
Grams per literGepotidacin 1500 mg
Day 3, n=19-3.4 ± 8.15
Day 5, n=18-0.6 ± 9.34
Days 10 to 13, n=17-8.2 ± 7.40
SecondaryChange From Baseline in Hematology Parameter: Hematocrit

Blood samples were collected to analyze the hematology parameter: Hematocrit. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

Time frame:
Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Reported as:
Mean · Percentage of red blood cells in blood
Change From Baseline in Hematology Parameter: Hematocrit
Percentage of red blood cells in bloodGepotidacin 1500 mg
Day 3, n=190.75 ± 3.186
Day 5, n=18-0.54 ± 3.643
Days 10 to 13, n=17-2.30 ± 2.956
SecondaryChange From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Hemoglobin

Blood samples were collected to analyze the hematology parameter: Erythrocyte Mean Corpuscular Hemoglobin. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

Time frame:
Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Reported as:
Mean · Picogram
Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Hemoglobin
PicogramGepotidacin 1500 mg
Day 3, n=190.13 ± 0.564
Day 5, n=180.03 ± 0.465
Days 10 to 13, n=170.16 ± 0.348
SecondaryChange From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Volume

Blood samples were collected to analyze the hematology parameter: Erythrocyte Mean Corpuscular Volume. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

Time frame:
Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Reported as:
Mean · Femtoliter
Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Volume
FemtoliterGepotidacin 1500 mg
Day 3, n=194.53 ± 5.814
Day 5, n=18-0.72 ± 4.668
Days 10 to 13, n=171.14 ± 6.252
SecondaryChange From Baseline in Hematology Parameter: Red Blood Cell Count

Blood samples were collected to analyze the hematology parameter: Red blood cell count. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

Time frame:
Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Reported as:
Mean · 10^12 cells per liter
Change From Baseline in Hematology Parameter: Red Blood Cell Count
10^12 cells per literGepotidacin 1500 mg
Day 3, n=19-0.135 ± 0.2574
Day 5, n=18-0.031 ± 0.3060
Days 10 to 13, n=17-0.298 ± 0.2552
SecondaryChange From Baseline in Clinical Chemistry Parameters: Albumin and Protein

Blood samples were collected to analyze the chemistry parameters: Albumin and Protein. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

Time frame:
Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Reported as:
Mean · Grams per liter
Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein
Grams per literGepotidacin 1500 mg
Albumin: Day 3, n=22-2.0 ± 2.45
Albumin: Day 5, n=21-1.4 ± 2.71
Albumin: Days 10 to 13, n=20-1.3 ± 2.90
Protein: Day 3, n=22-3.0 ± 3.82
Protein: Day 5, n=21-2.6 ± 4.52
Protein: Days 10 to 13, n=20-2.4 ± 5.13
SecondaryChange From Baseline in Clinical Chemistry Parameters: Creatinine and Bilirubin

Blood samples were collected to analyze the chemistry parameters: Creatinine and Bilirubin. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

Time frame:
Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Reported as:
Mean · Micromoles per liter
Change From Baseline in Clinical Chemistry Parameters: Creatinine and Bilirubin
Micromoles per literGepotidacin 1500 mg
Creatinine: Day 3, n=222.411 ± 9.9048
Creatinine: Day 5, n=211.684 ± 7.7162
Creatinine: Days 10 to 13, n=200.442 ± 7.2981
Bilirubin: Day 3, n=14-1.8932 ± 4.06405
Bilirubin: Day 5, n=15-1.6986 ± 3.41356
Bilirubin: Days 10 to 13, n=14-1.6856 ± 3.42845
SecondaryChange From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (ALP)

Blood samples were collected to analyze the chemistry parameters: ALT, AST and ALP. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

Time frame:
Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Reported as:
Mean · International units per liter
Change From Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Alkaline Phosphatase (ALP)
International units per literGepotidacin 1500 mg
ALT: Day 3, n=22-1.5 ± 4.99
ALT: Day 5, n=211.7 ± 7.51
ALT: Days 10 to 13, n=201.7 ± 7.44
AST: Day 3, n=22-1.3 ± 3.22
AST: Day 5, n=211.3 ± 3.77
AST: Days 10 to 13, n=202.1 ± 3.22
ALP: Day 3, n=22-3.3 ± 7.91
ALP: Day 5, n=21-4.3 ± 8.84
ALP: Days 10 to 13, n=20-4.5 ± 7.76
SecondaryChange From Baseline in Clinical Chemistry Parameters: Glucose, Calcium, Chloride, Potassium, Sodium and Urea

Blood samples were collected to analyze the chemistry parameters: Glucose, Calcium, Chloride, Potassium, Sodium and Urea. Baseline was defined as Day -1. Change from Baseline was calculated by subtracting the post-dose visit value from the Baseline value. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13.

Time frame:
Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Reported as:
Mean · Millimoles per liter
Change From Baseline in Clinical Chemistry Parameters: Glucose, Calcium, Chloride, Potassium, Sodium and Urea
Millimoles per literGepotidacin 1500 mg
Day 3, Glucose, n=220.13121 ± 1.237031
Day 5, Glucose, n=210.87495 ± 1.382514
Days 10 to 13, Glucose, n=20-0.05274 ± 0.498607
Day 3, Calcium, n=22-0.05330 ± 0.075175
Day 5, Calcium, n=21-0.05228 ± 0.093648
Days 10 to 13, Calcium, n=20-0.07110 ± 0.095536
Day 3, Chloride, n=220.5 ± 2.42
Day 5, Chloride, n=210.3 ± 2.90
Days 10 to 13, Chloride, n=200.3 ± 2.15
Day 3, Potassium, n=220.04 ± 0.359
Day 5, Potassium, n=21-0.05 ± 0.425
Days 10 to 13, Potassium, n=200.01 ± 0.419
Day 3, Sodium, n=22-0.7 ± 2.29
Day 5, Sodium, n=21-1.6 ± 2.13
Days 10 to 13, Sodium, n=20-0.9 ± 1.65
Day 3, Urea, n=220.1298 ± 1.15836
Day 5, Urea, n=210.0680 ± 1.06275
Days 10 to 13, Urea, n=200.3927 ± 1.18063
SecondaryNumber of Participants With Urinalysis Dipstick Results: Glucose and Nitrites

Urine samples were collected at indicated time points to analyze parameters including glucose and nitrites by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative and positive in the urine sample. Baseline was defined as Day -1. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13. Only categories with significant values have been presented.

Time frame:
Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Reported as:
Count of participants · Participants
Number of Participants With Urinalysis Dipstick Results: Glucose and Nitrites
ParticipantsGepotidacin 1500 mg
Baseline:Glucose,Negative,n=2222
Day 3:Glucose,Negative,n=2222
Day 5:Glucose,Negative,n=2121
Days 10 to 13:Glucose,Negative,n=2020
Baseline: Nitrites,Negative,n=2213
Baseline: Nitrites,Positive,n=229
Day 3: Nitrites,Negative,n=2222
Day 5: Nitrites,Negative,n=2121
Days 10 to 13: Nitrites,Negative,n=2020
SecondaryNumber of Participants With Urinalysis Dipstick Results: Ketones

Urine samples were collected at indicated time points to analyze parameter including ketones by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative, 5 indicates 5 milligrams per deciliter (mg/dL) and 20 indicates 20 mg/dL in the urine sample. Baseline was defined as Day -1. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13. Only categories with significant values have been presented.

Time frame:
Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Reported as:
Count of participants · Participants
Number of Participants With Urinalysis Dipstick Results: Ketones
ParticipantsGepotidacin 1500 mg
Baseline:Ketones,Negative,n=2221
Baseline:Ketones,20,n=221
Day 3:Ketones,Negative,n=2222
Day 5:Ketones,Negative,n=2121
Days 10 to 13:Ketones,Negative,n=2018
Days 10 to 13:Ketones,5,n=202
SecondaryNumber of Participants With Urinalysis Dipstick Results: Leukocyte Esterase

Urine samples were collected at indicated time points to analyze parameter including leukocyte esterase by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative, Trace indicates 15 Leukocytes per microliter (Leuko/mcL), Small indicates 70 Leuko/mcL, Moderate indicates 125 Leuko/mcL and Large indicates 500 Leuko/mcL in the urine sample. Baseline was defined as Day -1. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13. Only categories with significant values have been presented.

Time frame:
Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Reported as:
Count of participants · Participants
Number of Participants With Urinalysis Dipstick Results: Leukocyte Esterase
ParticipantsGepotidacin 1500 mg
Baseline:Leukocyte esterase,Negative,n=224
Baseline:Leukocyte esterase,Trace,n=222
Baseline:Leukocyte esterase,Small,n=224
Baseline:Leukocyte esterase,Moderate,n=221
Baseline:Leukocyte esterase,Large,n=2211
Day 3:Leukocyte esterase,Negative,n=2219
Day 3:Leukocyte esterase,Small,n=221
Day 3:Leukocyte esterase,Moderate,n=222
Day 5:Leukocyte esterase,Negative,n=2116
Day 5:Leukocyte esterase,Trace,n=214
Day 5:Leukocyte esterase,Small,n=211
Days 10 to 13:Leukocyte esterase,Negative,n=2019
Days 10 to 13:Leukocyte esterase,Trace,n=201
SecondaryNumber of Participants With Urinalysis Dipstick Results: Occult Blood

Urine samples were collected at indicated time points to analyze parameter including occult blood by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative, Small indicates 25 Erythrocytes per microliter (Ery/mcL), Moderate indicates 50 Ery/mcL and Large indicates 250 Ery/mcL in the urine sample. Baseline was defined as Day -1. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13. Only categories with significant values have been presented.

Time frame:
Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Reported as:
Count of participants · Participants
Number of Participants With Urinalysis Dipstick Results: Occult Blood
ParticipantsGepotidacin 1500 mg
Baseline:Occult blood,Negative,n=226
Baseline:Occult blood,Small,n=2210
Baseline:Occult blood,Moderate,n=223
Baseline:Occult blood,Large,n=223
Day 3:Occult blood,Negative,n=2219
Day 3:Occult blood,Small,n=221
Day 3:Occult blood,Moderate,n=221
Day 3:Occult blood,Large,n=221
Day 5:Occult blood,Negative,n=2117
Day 5:Occult blood,Small,n=212
Day 5:Occult blood,Moderate,n=212
Days 10 to 13:Occult blood,Negative,n=2018
Days 10 to 13:Occult blood,Small,n=202
SecondaryNumber of Participants With Urinalysis Dipstick Results: Protein

Urine samples were collected at indicated time points to analyze parameter including protein by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative indicates \<10 mg/dL, 1+ indicates 30 mg/dL and 2+ indicates 100 mg/dL in the urine sample. Baseline was defined as Day -1. Assessment at Test-of-cure visit was conducted between any day of Days 10 to 13. Only categories with significant values have been presented.

Time frame:
Baseline, Day 3, Day 5 and Days 10 to 13 (Test-of-cure visit)
Reported as:
Count of participants · Participants
Number of Participants With Urinalysis Dipstick Results: Protein
ParticipantsGepotidacin 1500 mg
Baseline: Protein,Negative,n=2211
Baseline: Protein,1+,n=2210
Baseline: Protein,2+,n=221
Day 3: Protein,Negative,n=2218
Day 3: Protein,1+,n=224
Day 5: Protein,Negative,n=2116
Day 5: Protein,1+,n=215
Days 10 to 13: Protein,Negative,n=2018
Days 10 to 13: Protein,1+,n=202
SecondaryNumber of Participants With Abnormal Physical Examination Findings

Physical examinations included assessments of the respiratory, cardiovascular, abdominal, gastrointestinal, neurological and urogenital systems. This analysis was planned but data was not collected and captured in the database.

Time frame:
Up to Day 31

No measurements were reported for this outcome.

Adverse events

Collected over Non-SAEs and SAEs were collected from start of the treatment (Day 1) up to Day 31. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Gepotidacin 1500 mg0/22 (0%)1/22 (4.5%)21/22 (95.5%)
Most frequent serious events
Most frequent serious events
EventGepotidacin 1500 mg
Major depressionPsychiatric disorders1/22
Most frequent other events
Most frequent other events
EventGepotidacin 1500 mg
DiarrhoeaGastrointestinal disorders18/22
NauseaGastrointestinal disorders17/22
VomitingGastrointestinal disorders5/22
HeadacheNervous system disorders5/22
Viral upper respiratory tract infectionInfections and infestations2/22
Vulvovaginal mycotic infectionInfections and infestations2/22
Back painMusculoskeletal and connective tissue disorders2/22
Chest discomfortGeneral disorders2/22

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Gepotidacin 1500 mg
Mean37.1 ± 12.26
Sex: Female, Male
Sex: Female, Male(Participants)Gepotidacin 1500 mg
Female22
Male0
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Gepotidacin 1500 mg
Black or African American4
White - White/Caucasian/European Heritage18
08

Study locations

1 site
  • GSK Investigational Site
    La Mesa, California 91942, United States
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References and documents

Publications

  • Overcash JS, Tiffany CA, Scangarella-Oman NE, Perry CR, Tao Y, Hossain M, Barth A, Dumont EF. Phase 2a Pharmacokinetic, Safety, and Exploratory Efficacy Evaluation of Oral Gepotidacin (GSK2140944) in Female Participants with Uncomplicated Urinary Tract Infection (Acute Uncomplicated Cystitis). Antimicrob Agents Chemother. 2020 Jun 23;64(7):e00199-20. doi: 10.1128/AAC.00199-20. Print 2020 Jun 23. PubMed 32284384 ↗
  • Nuzzo A, Van Horn S, Traini C, Perry CR, Dumont EF, Scangarella-Oman NE, Gardiner DF, Brown JR. Microbiome recovery in adult females with uncomplicated urinary tract infections in a randomised phase 2A trial of the novel antibiotic gepotidacin (GSK140944). BMC Microbiol. 2021 Jun 15;21(1):181. doi: 10.1186/s12866-021-02245-8. PubMed 34130619 ↗

Study documents

  • Study protocol · May 10, 2018
  • Statistical analysis plan · Nov 14, 2018

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, Statistical analysis plan, Informed consent form, Clinical study report

Time frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)

Access criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Data sharing details ↗ · clinicalstudydatarequest.com

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 29, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT03568942
Lead sponsor
GlaxoSmithKline
Collaborators
Biomedical Advanced Research and Development Authority
Responsible party
Sponsor
First posted
Jun 26, 2018
Start date
Jul 23, 2018
Primary completion
Jan 7, 2019
Completion
Jan 7, 2019
Results posted
Jan 7, 2020
Last update
Jun 29, 2020

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

Oversight

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

Not currently enrolling

This study is completed, as verified in Jun 2020. You cannot join it, but the record below documents what was studied.

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Discussion

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