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CompletedNCT05630833EAGLE-JUpdated Mar 17, 2025Results posted

A Study to Investigate the Efficacy and Safety With Gepotidacin in Japanese Female Participants With Uncomplicated Urinary Tract Infection (Acute Cystitis)

A Phase 3 interventional study of Gepotidacin and Nitrofurantoin in Urinary Tract Infections, sponsored by GlaxoSmithKline. Completed at 27 sites in Japan. Open to female participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2025-03-17.

Sponsored by GlaxoSmithKline · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
380
Allocation
Randomized
Ages
12 Years and older
Sex
Female
01

Study summary

The purpose of this study is to evaluate the consistency of therapeutic response of gepotidacin in female participants with acute uncomplicated cystitis with qualifying bacterial uropathogen(s) at baseline that all are susceptible to nitrofurantoin in Japan, with that from global studies (Studies 204989 [NCT04020341] and 212390 [NCT04187144]).

02

Conditions studied

  • Urinary Tract Infections

Keywords

  • Acute cystitis
  • Efficacy
  • Gepotidacin
  • Nitrofurantoin
  • Urinary Tract Infection
  • Japanese Female
03

Who can participate

Ages eligible
12 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

Inclusion criteria

  • The participant has a body weight >=40 kilograms (kg).
  • The participant has 2 or more of the following clinical signs and symptoms of acute cystitis with onset less than (\<) 96 hours prior to study entry: dysuria, frequency, urgency, or lower abdominal pain.
  • The participant has nitrite or pyuria (greater than [>]15 white blood cell [WBC]/high-power field [HPF] or the presence of 3 plus (+) /large leukocyte esterase) from a pretreatment clean-catch midstream urine sample based on local laboratory procedures.
  • The participant is capable of giving signed informed consent/assent.

Exclusion criteria

Exclusion Criteria:

  • The participant resides in a nursing home or dependent care type facility.
  • The participant has a body mass index >=40.0 kilogram per meter square (kg/m\^2) or a body mass index >=35.0 kg/m\^2 and is experiencing obesity-related health conditions such as uncontrolled high blood pressure or uncontrolled diabetes.
  • The participant is immunocompromised or has altered immune defenses that may predispose the participant to a higher risk of treatment failure and/or complications.

  • The participant has any of the following:

    • Poorly controlled asthma or chronic obstructive pulmonary disease; Acute severe pain; Active peptic ulcer disease; Parkinson disease; Myasthenia gravis; a history of seizure disorder requiring medications for control (this does not include a history of childhood febrile seizures); Or
    • Known acute porphyria.
    • Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study intervention.
  • The participant has a known glucose-6-phosphate dehydrogenase deficiency.
  • The participant, in the judgment of the investigator, would not be able or willing to comply with the protocol or complete study follow-up.
  • The participant has acute uncomplicated 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 Enterobacterales (other than E. coli) as the contributing pathogen.
  • The participant has symptoms known or suspected to be caused by another disease process, such as asymptomatic bacteriuria, overactive bladder, chronic incontinence, or chronic interstitial cystitis, that may interfere with the clinical efficacy assessments or preclude complete resolution of acute cystitis symptoms.
  • The participant has an anatomical or physiological anomaly that predisposes the participant 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 participant has a history of anatomical or functional abnormalities of the urinary tract (e.g., chronic vesicoureteral reflux, detrusor insufficiency).
  • The participant has an indwelling catheter, nephrostomy, ureter stent, or other foreign material in the urinary tract.
  • The participant who, in the opinion of the investigator, has an otherwise complicated UTI, an active upper UTI (e.g., pyelonephritis, urosepsis), signs and symptom onset >=96 hours before study entry, or a temperature >=38 Degrees Celsius [°C], flank pain, chills, or any other manifestations suggestive of upper UTI.
  • The participant has known anuria, oliguria, or significant impairment of renal function (creatinine clearance \<60 milliliters per minute (mL/min) or clinically significant elevated serum creatinine as determined by the investigator).
  • The participant presents with vaginal discharge at Baseline (e.g., suspected sexually transmitted disease).
  • The participant has congenital long QT syndrome or known prolongation of the corrected QT (QTc) interval.
  • The participant has uncompensated heart failure.
  • The participant has severe left ventricular hypertrophy.
  • The participant has a family history of QT prolongation or sudden death.
  • The participant has a recent history of vasovagal syncope or episodes of symptomatic bradycardia or brady arrhythmia within the last 12 months.
  • The participant is taking QT-prolonging drugs or drugs known to increase the risk of torsades de pointes (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 participant is taking a strong cytochrome P450 enzyme 3A4 (CYP3A4) inhibitor.
  • For any participant >=12 to \<18 years of age, the participant has an abnormal ECG reading at Baseline.
  • The participant has a QTc >450 msec or a QTc >480 msec for participants with bundle branch block.
  • The participant has a documented or recent history of uncorrected hypokalemia within the past 3 months.
  • The participant has a known alanine aminotransferase (ALT) value >2 times upper limit of normal (ULN).
  • The participant has a known total bilirubin value >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent [%]).
  • The participant has cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice.
  • The participant has a previous history of cholestatic jaundice/hepatic dysfunction associated with nitrofurantoin.
  • The participant has received treatment with other systemic antimicrobials or systemic antifungals within 1 week before study entry.
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
380 participants (actual)

Study arms

  • Experimental
    Gepotidacin + Placebo

    Drug: Gepotidacin · Drug: Placebo

  • Active comparator
    Nitrofurantoin + Placebo

    Drug: Nitrofurantoin · Drug: Placebo

Interventions

  • DrugGepotidacin

    Gepotidacin will be administered.

  • DrugNitrofurantoin

    Nitrofurantoin will be administered.

  • DrugPlacebo

    Placebo will be administered.

05

What researchers measure

Primary outcomes

  1. Number of Participants With Therapeutic Response (TR) (Combined Per-participant Microbiological and Clinical Success) for Gepotidacin at the Test of Cure (TOC) Visit

    TR at TOC (success/failure) is a measure of the overall efficacy response. A therapeutic success at TOC referred to participant who have been deemed both a microbiological success (reduction of all qualifying bacterial uropathogens recovered at BL to \<10\^3 colony forming units per milliliter \[CFU/mL\] without receiving other systemic antimicrobials \[AB\] before the TOC visit) and a clinical success (resolution of symptoms of acute cystitis present at BL and no new symptoms without receiving other AB before the TOC visit \[or AB for uUTI on day of TOC visit\]). Lack of clinical or microbiological success (including missing outcome assessments) was considered as therapeutic failure.

    Time frame: At TOC visit (Days 9 to 16)

Secondary outcomes

  1. Number of Participants With Therapeutic Response (TR) of Gepotidacin Compared to Nitrofurantoin at the Test of Cure (TOC) Visit - Micro-ITT NTF-S Population

    TR at TOC (success/failure) is a measure of the overall efficacy response. A therapeutic success at TOC referred to participant who have been deemed both a microbiological success (reduction of all qualifying bacterial uropathogens recovered at BL to \<10\^3 colony forming units per milliliter \[CFU/mL\] without receiving other systemic antimicrobials \[AB\] before the TOC visit) and a clinical success (resolution of symptoms of acute cystitis present at BL and no new symptoms without receiving other AB before the TOC visit \[or AB for uUTI on day of TOC visit\]). Lack of clinical or microbiological success (including missing outcome assessments) was considered as therapeutic failure.

    Time frame: At TOC visit (Days 9 to 16)

  2. Number of Participants With Clinical Outcome at the TOC Visit - Micro-ITT NTF-S Population

    Clinical outcome at TOC was categorized as clinical resolution, clinical improvement, clinical worsening and unable to determine. Clinical resolution at TOC was defined as resolution of signs and symptoms of acute cystitis present at BL (and no symptoms) without receiving any other AB before the TOC visit. Clinical improvement at TOC was defined as improvement (but not complete resolution) in total symptom score (CSS) from BL, without receiving any other AB before the TOC visit. Clinical worsening at TOC was defined as worsening or no change in CSS from BL or received other AB for the current infection (uUTI) before or on the date of the TOC visit. Unable to determine outcome criteria were: BL score is missing (and thus improvement/worsening cannot be determined), TOC assessment is missing, or receipt of other AB not for the current infection before the TOC visit (unless clinical worsening outcome criteria were met).

    Time frame: At TOC visit (Days 9 to 16)

  3. Number of Participants With Clinical Response at the TOC Visit - Micro-ITT NTF-S Population

    Clinical response at TOC was categorized as clinical success and clinical failure. Clinical success at TOC was defined as resolution of symptoms of acute cystitis present at BL (and no new symptoms), without receiving any other AB before the TOC visit. Lack of resolution, including receipt of an AB for uUTI at the TOC visit, or a missing outcome assessment was defined as Clinical Failure at TOC.

    Time frame: At TOC visit (Days 9 to 16)

  4. Number of Participants With Microbiological Outcome (MO) at the TOC Visit -Micro-ITT NTF-S Population

    Participant-level MO at TOC was categorized as microbiological eradication (ME), microbiological persistence (MP), microbiological recurrence (MR) and unable to determine (UTD). ME at TOC was defined as all baseline qualifying uropathogens (QUP) have an outcome of eradication at TOC (i.e., \<10\^3 CFU/mL without the participant receiving other systemic antimicrobials before the TOC Visit). MP at TOC was defined as at least 1 QUP has an outcome of persistence (≥10\^3 CFU/mL) at TOC. MR at TOC was defined as at least 1 QUP had an outcome of recurrence and none have an outcome of persistence at TOC. UTD at TOC was defined as all QUP outcomes are UTD at TOC.

    Time frame: At TOC visit (Days 9 to 16)

  5. Number of Participants With Microbiological Response at the TOC Visit -Micro-ITT NTF-S Population

    Participant-level microbiological response at TOC was categorized as microbiological success and microbiological failure. Microbiological success at TOC was defined as all baseline qualifying uropathogens (QUP) had a microbiological outcome of eradication at TOC visit. Microbiological failure was defined as lack of microbiological success, including those participants with UTD outcomes.

    Time frame: At TOC visit (Days 9 to 16)

  6. Number of Participants With Therapeutic Response (TR) at the TOC Visit

    TR at TOC (success/failure) is a measure of the overall efficacy response. A therapeutic success at TOC referred to participant who have been deemed both a microbiological success (reduction of all qualifying bacterial uropathogens recovered at BL to \<10\^3 colony forming units per milliliter \[CFU/mL\] without receiving other systemic antimicrobials \[AB\] before the TOC visit) and a clinical success (resolution of symptoms of acute cystitis present at BL and no new symptoms without receiving other AB before the TOC visit \[or AB for uUTI on day of TOC visit\]). Lack of clinical or microbiological success (including missing outcome assessments) was considered as therapeutic failure.

    Time frame: At TOC visit (Days 9 to 16)

  7. Number of Participants With Clinical Outcome at the TOC Visit

    Clinical outcome at TOC was categorized as clinical resolution, clinical improvement, clinical worsening and unable to determine. Clinical resolution at TOC was defined as resolution of signs and symptoms of acute cystitis present at BL (and no symptoms) without receiving any other AB before the TOC visit. Clinical improvement at TOC was defined as improvement (but not complete resolution) in CSS from BL, without receiving any other AB before the TOC visit. Clinical worsening at TOC was defined as worsening or no change in CSS from BL or received other AB for the current infection (uUTI) before or on the date of the TOC visit. Unable to determine outcome criteria were: BL score is missing (and thus improvement/worsening cannot be determined), TOC assessment is missing, or receipt of other AB not for the current infection before the TOC visit (unless clinical worsening outcome criteria were met).

    Time frame: At TOC visit (Days 9 to 16)

  8. Number of Participants With Clinical Response at the TOC Visit

    Clinical response at TOC was categorized as clinical success and clinical failure. Clinical success at TOC was defined as resolution of symptoms of acute cystitis present at BL (and no new symptoms), without receiving any other AB before the TOC visit. Lack of resolution, including receipt of an AB for uUTI at the TOC visit, or a missing outcome assessment was defined as Clinical Failure at TOC.

    Time frame: At TOC visit (Days 9 to 16)

  9. Number of Participants With Microbiological Outcome at the TOC Visit

    Participant-level MO at TOC was categorized as microbiological eradication (ME), microbiological persistence (MP), microbiological recurrence (MR) and unable to determine (UTD). ME at TOC was defined as all baseline qualifying uropathogens (QUP) have an outcome of eradication at TOC (i.e., \<10\^3 CFU/mL without the participant receiving other systemic antimicrobials before the TOC Visit). MP at TOC was defined as at least 1 QUP has an outcome of persistence (≥10\^3 CFU/mL) at TOC. MR at TOC was defined as at least 1 QUP had an outcome of recurrence and none have an outcome of persistence at TOC. UTD at TOC was defined as all QUP outcomes are UTD at TOC.

    Time frame: At TOC visit (Days 9 to 16)

  10. Number of Participants With Microbiological Response at the TOC Visit

    Participant-level microbiological response at TOC was categorized as microbiological success and microbiological failure. Microbiological success at TOC was defined as all baseline qualifying uropathogens (QUP) had a microbiological outcome of eradication at TOC visit. Microbiological failure was defined as lack of microbiological success, including those participants with UTD outcomes.

    Time frame: At TOC visit (Days 9 to 16)

  11. Number of Participants With Investigator Assessed Clinical Response

    Clinical response as assessed by investigator at TOC was categorized as clinical success and clinical failure. Clinical success at TOC was defined as sufficient resolution of acute cystitis signs and symptoms such that no additional systemic AB was required for the current infection. No apparent response to treatment, use of additional systemic AB for the current infection and death related to acute cystitis prior to the visit was considered as Clinical failure. Indeterminate/Missing was defined as participant lost to follow-up and/or the clinical assessment was not undertaken, use of confounding systemic AB for another infection, and death prior to the visit where acute cystitis was clearly noncontributory.

    Time frame: At TOC visit (Days 9 to 16)

  12. Number of Participants With Treatment-emergent Adverse Events (TEAEs)

    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 AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. TEAE is defined as any AE with an onset date on or after treatment start date/time. AEs were coded using Medical Dictionary for Regulatory Activities (MedDRA).

    Time frame: From first dose (Day 1) to Follow-up visit (Days 21 to 31)

  13. Number of Participants With Serious AEs (SAEs) and Adverse Events of Special Interest (AESIs)

    An SAE is defined as any untoward medical occurrence that, at any dose may result in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity or is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. Adverse events of special interest (AESI) for gepotidacin included clostridium difficile, cardiovascular \& gastrointestinal events and potential acetylcholinesterase-inhibition AESIs. SAEs were coded using MedDRA.

    Time frame: From first dose (Day 1) to Follow-up visit (Days 21 to 31)

  14. Number of Participants With Urinalysis Dipstick Results

    Urine samples were collected for urinalysis: Urine Glucose (GLU), Urine Ketones (KET), Urine Nitrite (NIT) and Urine Protein (PRO). Baseline is defined as the latest pre-dose assessment with a non-missing value. The dipstick test gives results in a semi-quantitative manner, and results can be read as Negative, Positive, 2777.55 micromole per liter (µmol/l), \>=27775.5 µmol/l, 8332.65 µmol/l, 5 milligram/dl (mg/dL), 20 mg/dL, \>=80 mg/dL, 300 mg/dL, 1000 mg/dL, \>=5000 mg/dL indicating concentrations in the urine sample. In the row title (GLU, Baseline, 2777.55 micromole per liter), GLU indicates parameter, Baseline is the visit and 2777.55 micromole per liter indicates the concentration/presence in the urine sample. Data is presented in similar way for other parameters.

    Time frame: Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)

  15. Change From Baseline (CFB) in Electrocardiograms (ECGs): Heart Rate

    Triplicate 12-lead ECGs (over an approximate 5 to 10 minute period) were performed using an ECG machine that automatically calculated the heart rate, measured PR, QRS, QT, and QT interval corrected for heart rate according to Fridericia's formula (QTcF). Baseline is defined as the latest pre-dose assessment with a non-missing value.

    Time frame: Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)

  16. Change From Baseline (CFB) in Electrocardiograms (ECGs): PR, QRS, QT and QTcF

    Triplicate 12-lead ECGs (over an approximate 5 to 10 minute period) were performed using an ECG machine that automatically calculated the heart rate, measured PR, QRS, QT, and QTcF. Baseline is defined as the latest pre-dose assessment with a non-missing value.

    Time frame: Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)

  17. Change From Baseline (CFB) in Vital Sign: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

    SBP and DBP were measured in a semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment with a non-missing value.

    Time frame: Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)

  18. Change From Baseline (CFB) in Vital Sign: Temperature

    Temperature was measured in a semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment with a non-missing value.

    Time frame: Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)

  19. Change From Baseline (CFB) in Vital Sign: Pulse Rate

    Pulse rate was measured in a semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment with a non-missing value.

    Time frame: Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)

  20. Plasma Concentrations of Gepotidacin

    Blood samples were collected for plasma concentration of Gepotidacin.

    Time frame: Baseline (Day 1 at 0-2h & >2h Post dose), Day 2 to 5 at Pre-dose, 0-2h & >2h Post Dose

  21. Urine Concentrations of Gepotidacin

    Urine samples were collected for urine concentration of Gepotidacin.

    Time frame: Baseline (Day 1 at 0-2h & >2h Post dose), Day 2 to 5 at Pre-dose, 0-2h & >2h Post Dose

  22. Change From Baseline (CFB) in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets at On Therapy and Test of Cure Visit

    Blood samples were collected for the analysis of hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, and platelets. Baseline is defined as the latest pre-dose assessment with a non-missing value.

    Time frame: Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)

  23. Change From Baseline (CFB) in Hematology Parameter-Hemoglobin Level at On Therapy and Test of Cure Visit

    Blood samples were collected for the analysis of hemoglobin level. Baseline is defined as the latest pre-dose assessment with a non-missing value

    Time frame: Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)

  24. Change From Baseline (CFB) in Hematology Parameter- Hematocrit Level at On Therapy and Test of Cure Visit

    Blood samples were collected for the analysis of hematocrit level. Baseline is defined as the latest pre-dose assessment with a non-missing value.

    Time frame: Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)

  25. Change From Baseline (CFB) in Hematology Parameter- Erythrocytes Count at On Therapy and Test of Cure Visit

    Blood samples were collected for the analysis of erythrocytes count. Baseline is defined as the latest pre-dose assessment with a non-missing value.

    Time frame: Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)

  26. Change From Baseline (CFB) in Hematology Parameter - Mean Corpuscular Hemoglobin (MCH) at On Therapy and Test of Cure Visit

    Blood samples were collected for the analysis of MCH. Baseline is defined as the latest pre-dose assessment with a non-missing value.

    Time frame: Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)

  27. Change From Baseline (CFB) in Hematology Parameter - Mean Corpuscular Volume (MCV) at On Therapy and Test of Cure Visit

    Blood samples were collected for the analysis of MCV. Baseline is defined as the latest pre-dose assessment with a non-missing value.

    Time frame: Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)

  28. Change From Baseline (CFB) in Clinical Chemistry Parameters - Calcium, Glucose, Potassium, Magnesium, Phosphate, Sodium, and Urea Nitrogen Levels at On Therapy and Test of Cure Visit

    Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.

    Time frame: Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)

  29. Change From Baseline (CFB) in Clinical Chemistry Parameters - Serum Chloride at On Therapy and Test of Cure Visit

    Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value

    Time frame: Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)

  30. Change From Baseline (CFB) in Clinical Chemistry Parameters - Direct Bilirubin, Total Bilirubin and Creatinine Levels at On Therapy and Test of Cure Visit

    Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.

    Time frame: Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)

  31. Change From Baseline (CFB) in Clinical Chemistry Parameters - Creatinine Clearance at On Therapy and Test of Cure Visit

    Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.

    Time frame: Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)

  32. Change From Baseline (CFB) in Clinical Chemistry Parameters - Albumin and Protein Levels at On Therapy and Test of Cure Visit

    Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.

    Time frame: Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)

  33. Change From Baseline (CFB) in Clinical Chemistry Parameters - Alkaline Phosphatase (ALP) and Alanine Aminotransferase (ALT) Levels at On Therapy and Test of Cure Visit

    Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.

    Time frame: Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)

  34. Change From Baseline (CFB) in Clinical Chemistry Parameter - Aspartate Aminotransferase (AST) Levels at On Therapy and Test of Cure Visit

    Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.

    Time frame: Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)

06

Results

Posted Mar 17, 2025
Limitations and caveats
GlaxoSmithKline (GSK) was informed of suspected GCP violations in a Japanese site management organization which provided site management services to one of the sites for this study, at which 6 participants were enrolled (5 gepotidacin participants; 1 nitrofurantoin participant). These 6 participants were excluded from the analysis due to data integrity issues including undeniable suspected data falsification that resulted in unreliable data.

Participant flow

Participant flow — Overall Study
MilestoneGepotidacinNitrofurantoin
Started28694
Itt population28193
Microbiological itt (micro-itt)8829
Micro-itt ntf-s8325
Micro-itt mdr183
Safety28193
Completed27992
Not completed72
Withdrew: Adverse event30
Withdrew: Lack of efficacy01
Withdrew: Lost to follow-up10
Withdrew: Withdrawal by subject31

Outcome measures

PrimaryNumber of Participants With Therapeutic Response (TR) (Combined Per-participant Microbiological and Clinical Success) for Gepotidacin at the Test of Cure (TOC) Visit

TR at TOC (success/failure) is a measure of the overall efficacy response. A therapeutic success at TOC referred to participant who have been deemed both a microbiological success (reduction of all qualifying bacterial uropathogens recovered at BL to \<10\^3 colony forming units per milliliter \[CFU/mL\] without receiving other systemic antimicrobials \[AB\] before the TOC visit) and a clinical success (resolution of symptoms of acute cystitis present at BL and no new symptoms without receiving other AB before the TOC visit \[or AB for uUTI on day of TOC visit\]). Lack of clinical or microbiological success (including missing outcome assessments) was considered as therapeutic failure.

Time frame:
At TOC visit (Days 9 to 16)
Reported as:
Count of participants · Participants
Number of Participants With Therapeutic Response (TR) (Combined Per-participant Microbiological and Clinical Success) for Gepotidacin at the Test of Cure (TOC) Visit
ParticipantsGepotidacin
Therapeutic Success69
Therapeutic Failure14
Statistical analysis
  • Gepotidacin · Lower 10th percentile (%): 48.2Lower 10th percentile of therapeutic successes was calculated from the predictive distribution.
SecondaryNumber of Participants With Therapeutic Response (TR) of Gepotidacin Compared to Nitrofurantoin at the Test of Cure (TOC) Visit - Micro-ITT NTF-S Population

TR at TOC (success/failure) is a measure of the overall efficacy response. A therapeutic success at TOC referred to participant who have been deemed both a microbiological success (reduction of all qualifying bacterial uropathogens recovered at BL to \<10\^3 colony forming units per milliliter \[CFU/mL\] without receiving other systemic antimicrobials \[AB\] before the TOC visit) and a clinical success (resolution of symptoms of acute cystitis present at BL and no new symptoms without receiving other AB before the TOC visit \[or AB for uUTI on day of TOC visit\]). Lack of clinical or microbiological success (including missing outcome assessments) was considered as therapeutic failure.

Time frame:
At TOC visit (Days 9 to 16)
Reported as:
Count of participants · Participants
Number of Participants With Therapeutic Response (TR) of Gepotidacin Compared to Nitrofurantoin at the Test of Cure (TOC) Visit - Micro-ITT NTF-S Population
ParticipantsGepotidacinNitrofurantoin
Therapeutic Success6917
Therapeutic Failure148
SecondaryNumber of Participants With Clinical Outcome at the TOC Visit - Micro-ITT NTF-S Population

Clinical outcome at TOC was categorized as clinical resolution, clinical improvement, clinical worsening and unable to determine. Clinical resolution at TOC was defined as resolution of signs and symptoms of acute cystitis present at BL (and no symptoms) without receiving any other AB before the TOC visit. Clinical improvement at TOC was defined as improvement (but not complete resolution) in total symptom score (CSS) from BL, without receiving any other AB before the TOC visit. Clinical worsening at TOC was defined as worsening or no change in CSS from BL or received other AB for the current infection (uUTI) before or on the date of the TOC visit. Unable to determine outcome criteria were: BL score is missing (and thus improvement/worsening cannot be determined), TOC assessment is missing, or receipt of other AB not for the current infection before the TOC visit (unless clinical worsening outcome criteria were met).

Time frame:
At TOC visit (Days 9 to 16)
Reported as:
Count of participants · Participants
Number of Participants With Clinical Outcome at the TOC Visit - Micro-ITT NTF-S Population
ParticipantsGepotidacinNitrofurantoin
Clinical Resolution7119
Clinical Improvement54
Clinical Worsening32
Unable To Determine40
SecondaryNumber of Participants With Clinical Response at the TOC Visit - Micro-ITT NTF-S Population

Clinical response at TOC was categorized as clinical success and clinical failure. Clinical success at TOC was defined as resolution of symptoms of acute cystitis present at BL (and no new symptoms), without receiving any other AB before the TOC visit. Lack of resolution, including receipt of an AB for uUTI at the TOC visit, or a missing outcome assessment was defined as Clinical Failure at TOC.

Time frame:
At TOC visit (Days 9 to 16)
Reported as:
Count of participants · Participants
Number of Participants With Clinical Response at the TOC Visit - Micro-ITT NTF-S Population
ParticipantsGepotidacinNitrofurantoin
Clinical Success7119
Clinical Failure126
SecondaryNumber of Participants With Microbiological Outcome (MO) at the TOC Visit -Micro-ITT NTF-S Population

Participant-level MO at TOC was categorized as microbiological eradication (ME), microbiological persistence (MP), microbiological recurrence (MR) and unable to determine (UTD). ME at TOC was defined as all baseline qualifying uropathogens (QUP) have an outcome of eradication at TOC (i.e., \<10\^3 CFU/mL without the participant receiving other systemic antimicrobials before the TOC Visit). MP at TOC was defined as at least 1 QUP has an outcome of persistence (≥10\^3 CFU/mL) at TOC. MR at TOC was defined as at least 1 QUP had an outcome of recurrence and none have an outcome of persistence at TOC. UTD at TOC was defined as all QUP outcomes are UTD at TOC.

Time frame:
At TOC visit (Days 9 to 16)
Reported as:
Count of participants · Participants
Number of Participants With Microbiological Outcome (MO) at the TOC Visit -Micro-ITT NTF-S Population
ParticipantsGepotidacinNitrofurantoin
Microbiological Eradication (ME)7420
Microbiological Persistence (MP)00
Microbiological Recurrence (MR)13
Unable To Determine (UTD)82
SecondaryNumber of Participants With Microbiological Response at the TOC Visit -Micro-ITT NTF-S Population

Participant-level microbiological response at TOC was categorized as microbiological success and microbiological failure. Microbiological success at TOC was defined as all baseline qualifying uropathogens (QUP) had a microbiological outcome of eradication at TOC visit. Microbiological failure was defined as lack of microbiological success, including those participants with UTD outcomes.

Time frame:
At TOC visit (Days 9 to 16)
Reported as:
Count of participants · Participants
Number of Participants With Microbiological Response at the TOC Visit -Micro-ITT NTF-S Population
ParticipantsGepotidacinNitrofurantoin
Microbiological Success7420
Microbiological Failure95
SecondaryNumber of Participants With Therapeutic Response (TR) at the TOC Visit

TR at TOC (success/failure) is a measure of the overall efficacy response. A therapeutic success at TOC referred to participant who have been deemed both a microbiological success (reduction of all qualifying bacterial uropathogens recovered at BL to \<10\^3 colony forming units per milliliter \[CFU/mL\] without receiving other systemic antimicrobials \[AB\] before the TOC visit) and a clinical success (resolution of symptoms of acute cystitis present at BL and no new symptoms without receiving other AB before the TOC visit \[or AB for uUTI on day of TOC visit\]). Lack of clinical or microbiological success (including missing outcome assessments) was considered as therapeutic failure.

Time frame:
At TOC visit (Days 9 to 16)
Reported as:
Count of participants · Participants
Number of Participants With Therapeutic Response (TR) at the TOC Visit
ParticipantsGepotidacinNitrofurantoin
Therapeutic Success142
Therapeutic Failure41
SecondaryNumber of Participants With Clinical Outcome at the TOC Visit

Clinical outcome at TOC was categorized as clinical resolution, clinical improvement, clinical worsening and unable to determine. Clinical resolution at TOC was defined as resolution of signs and symptoms of acute cystitis present at BL (and no symptoms) without receiving any other AB before the TOC visit. Clinical improvement at TOC was defined as improvement (but not complete resolution) in CSS from BL, without receiving any other AB before the TOC visit. Clinical worsening at TOC was defined as worsening or no change in CSS from BL or received other AB for the current infection (uUTI) before or on the date of the TOC visit. Unable to determine outcome criteria were: BL score is missing (and thus improvement/worsening cannot be determined), TOC assessment is missing, or receipt of other AB not for the current infection before the TOC visit (unless clinical worsening outcome criteria were met).

Time frame:
At TOC visit (Days 9 to 16)
Reported as:
Count of participants · Participants
Number of Participants With Clinical Outcome at the TOC Visit
ParticipantsGepotidacinNitrofurantoin
Clinical Resolution142
Clinical Improvement20
Clinical Worsening11
Unable To Determine10
SecondaryNumber of Participants With Clinical Response at the TOC Visit

Clinical response at TOC was categorized as clinical success and clinical failure. Clinical success at TOC was defined as resolution of symptoms of acute cystitis present at BL (and no new symptoms), without receiving any other AB before the TOC visit. Lack of resolution, including receipt of an AB for uUTI at the TOC visit, or a missing outcome assessment was defined as Clinical Failure at TOC.

Time frame:
At TOC visit (Days 9 to 16)
Reported as:
Count of participants · Participants
Number of Participants With Clinical Response at the TOC Visit
ParticipantsGepotidacinNitrofurantoin
Clinical Success142
Clinical Failure41
SecondaryNumber of Participants With Microbiological Outcome at the TOC Visit

Participant-level MO at TOC was categorized as microbiological eradication (ME), microbiological persistence (MP), microbiological recurrence (MR) and unable to determine (UTD). ME at TOC was defined as all baseline qualifying uropathogens (QUP) have an outcome of eradication at TOC (i.e., \<10\^3 CFU/mL without the participant receiving other systemic antimicrobials before the TOC Visit). MP at TOC was defined as at least 1 QUP has an outcome of persistence (≥10\^3 CFU/mL) at TOC. MR at TOC was defined as at least 1 QUP had an outcome of recurrence and none have an outcome of persistence at TOC. UTD at TOC was defined as all QUP outcomes are UTD at TOC.

Time frame:
At TOC visit (Days 9 to 16)
Reported as:
Count of participants · Participants
Number of Participants With Microbiological Outcome at the TOC Visit
ParticipantsGepotidacinNitrofurantoin
Microbiological Eradication162
Microbiological Persistence00
Microbiological Recurrence00
Unable To Determine21
SecondaryNumber of Participants With Microbiological Response at the TOC Visit

Participant-level microbiological response at TOC was categorized as microbiological success and microbiological failure. Microbiological success at TOC was defined as all baseline qualifying uropathogens (QUP) had a microbiological outcome of eradication at TOC visit. Microbiological failure was defined as lack of microbiological success, including those participants with UTD outcomes.

Time frame:
At TOC visit (Days 9 to 16)
Reported as:
Count of participants · Participants
Number of Participants With Microbiological Response at the TOC Visit
ParticipantsGepotidacinNitrofurantoin
Microbiological Success162
Microbiological Failure21
SecondaryNumber of Participants With Investigator Assessed Clinical Response

Clinical response as assessed by investigator at TOC was categorized as clinical success and clinical failure. Clinical success at TOC was defined as sufficient resolution of acute cystitis signs and symptoms such that no additional systemic AB was required for the current infection. No apparent response to treatment, use of additional systemic AB for the current infection and death related to acute cystitis prior to the visit was considered as Clinical failure. Indeterminate/Missing was defined as participant lost to follow-up and/or the clinical assessment was not undertaken, use of confounding systemic AB for another infection, and death prior to the visit where acute cystitis was clearly noncontributory.

Time frame:
At TOC visit (Days 9 to 16)
Reported as:
Count of participants · Participants
Number of Participants With Investigator Assessed Clinical Response
ParticipantsGepotidacinNitrofurantoin
Clinical Success24286
Clinical Failure286
Indeterminate/Missing111
SecondaryNumber of Participants With Treatment-emergent Adverse Events (TEAEs)

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 AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment. TEAE is defined as any AE with an onset date on or after treatment start date/time. AEs were coded using Medical Dictionary for Regulatory Activities (MedDRA).

Time frame:
From first dose (Day 1) to Follow-up visit (Days 21 to 31)
Reported as:
Count of participants · Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
ParticipantsGepotidacinNitrofurantoin
Number of Participants With Treatment-emergent Adverse Events (TEAEs)20118
SecondaryNumber of Participants With Serious AEs (SAEs) and Adverse Events of Special Interest (AESIs)

An SAE is defined as any untoward medical occurrence that, at any dose may result in death or is life-threatening or requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity or is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment or is associated with liver injury and impaired liver function. Adverse events of special interest (AESI) for gepotidacin included clostridium difficile, cardiovascular \& gastrointestinal events and potential acetylcholinesterase-inhibition AESIs. SAEs were coded using MedDRA.

Time frame:
From first dose (Day 1) to Follow-up visit (Days 21 to 31)
Reported as:
Count of participants · Participants
Number of Participants With Serious AEs (SAEs) and Adverse Events of Special Interest (AESIs)
ParticipantsGepotidacinNitrofurantoin
Serious AE (SAE)20
AE of Special Interest (AESIs)19112
SecondaryNumber of Participants With Urinalysis Dipstick Results

Urine samples were collected for urinalysis: Urine Glucose (GLU), Urine Ketones (KET), Urine Nitrite (NIT) and Urine Protein (PRO). Baseline is defined as the latest pre-dose assessment with a non-missing value. The dipstick test gives results in a semi-quantitative manner, and results can be read as Negative, Positive, 2777.55 micromole per liter (µmol/l), \>=27775.5 µmol/l, 8332.65 µmol/l, 5 milligram/dl (mg/dL), 20 mg/dL, \>=80 mg/dL, 300 mg/dL, 1000 mg/dL, \>=5000 mg/dL indicating concentrations in the urine sample. In the row title (GLU, Baseline, 2777.55 micromole per liter), GLU indicates parameter, Baseline is the visit and 2777.55 micromole per liter indicates the concentration/presence in the urine sample. Data is presented in similar way for other parameters.

Time frame:
Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)
Reported as:
Count of participants · Participants
Number of Participants With Urinalysis Dipstick Results
ParticipantsGepotidacinNitrofurantoin
GLU, Baseline, 2777.55 micromole per liter31
GLU, Baseline, >=27775.5 micromole per liter45
GLU, Baseline, NEGATIVE27387
GLU, On-Therapy, 2777.55 micromole per liter51
GLU, On-Therapy, 8332.65 micromole per liter20
GLU, On-Therapy, >=27775.5 micromole per liter26
GLU, On-Therapy, NEGATIVE26686
GLU, Test-of-Cure, 2777.55 micromole per liter13
GLU, Test-of-Cure, 8332.65 micromole per liter10
GLU, Test-of-Cure, >=27775.5 micromole per liter36
GLU, Test-of-Cure, NEGATIVE26783
KET, Baseline, 20 milligrams per deciliter101
KET, Baseline, 5 milligrams per deciliter2613
KET, Baseline, NEGATIVE24479
KET, On-Therapy, 20 milligrams per deciliter61
KET, On-Therapy, 5 milligrams per deciliter227
KET, On-Therapy, >=80 milligrams per deciliter01
KET, On-Therapy, NEGATIVE24784
KET, Test-of-Cure, 20 milligrams per deciliter10
KET, Test-of-Cure, 5 milligrams per deciliter1813
KET, Test-of-Cure, NEGATIVE25379
NIT, Baseline, NEGATIVE21275
NIT, Baseline, POSITIVE6818
NIT, On-Therapy, NEGATIVE27590
NIT, On-Therapy, POSITIVE03
NIT, Test-of-Cure, NEGATIVE25686
NIT, Test-of-Cure, POSITIVE166
PRO, Baseline, 1000 milligrams per deciliter4319
PRO Baseline, 300 milligrams per deciliter6325
PRO, Baseline, >=5000 milligrams per deciliter154
PRO, Baseline, NEGATIVE15945
PRO, On-Therapy, 1000 milligrams per deciliter121
PRO, On-Therapy, 300 milligrams per deciliter4617
PRO, On-Therapy, >=5000 milligrams per deciliter20
PRO, On-Therapy, NEGATIVE21575
PRO, Test-of-Cure, 1000 milligrams per deciliter131
PRO, Test-of-Cure, 300 milligrams per deciliter2411
PRO, Test-of-Cure, >=5000 milligrams per deciliter01
PRO, Test-of-Cure, NEGATIVE23579
SecondaryChange From Baseline (CFB) in Electrocardiograms (ECGs): Heart Rate

Triplicate 12-lead ECGs (over an approximate 5 to 10 minute period) were performed using an ECG machine that automatically calculated the heart rate, measured PR, QRS, QT, and QT interval corrected for heart rate according to Fridericia's formula (QTcF). Baseline is defined as the latest pre-dose assessment with a non-missing value.

Time frame:
Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)
Reported as:
Mean · beats/minute
Change From Baseline (CFB) in Electrocardiograms (ECGs): Heart Rate
beats/minuteGepotidacinNitrofurantoin
Baseline67.2 ± 10.1870.7 ± 13.29
CFB to On-Therapy-0.5 ± 7.84-3.3 ± 12.41
CFB to Test-of-Cure0.5 ± 8.44-1.6 ± 12.90
SecondaryChange From Baseline (CFB) in Electrocardiograms (ECGs): PR, QRS, QT and QTcF

Triplicate 12-lead ECGs (over an approximate 5 to 10 minute period) were performed using an ECG machine that automatically calculated the heart rate, measured PR, QRS, QT, and QTcF. Baseline is defined as the latest pre-dose assessment with a non-missing value.

Time frame:
Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)
Reported as:
Mean · Millisecond (msec)
Change From Baseline (CFB) in Electrocardiograms (ECGs): PR, QRS, QT and QTcF
Millisecond (msec)GepotidacinNitrofurantoin
PR, Baseline154.9 ± 17.88159.3 ± 16.68
PR, CFB to On-Therapy1.6 ± 12.181.4 ± 9.96
PR, CFB to Test-of-Cure0.3 ± 10.470.6 ± 10.49
QRS, Baseline88.1 ± 10.0689.8 ± 9.78
QRS, CFB to On-Therapy1.2 ± 3.770.0 ± 3.57
QRS, CFB to Test-of-Cure-0.6 ± 3.72-0.5 ± 3.57
QT, Baseline404.5 ± 28.16401.1 ± 28.22
QT, CFB to On-Therapy10.4 ± 23.674.8 ± 18.78
QT, CFB to Test-of-Cure-0.7 ± 24.533.4 ± 23.23
QTcF, Baseline418.3 ± 17.75423.2 ± 17.25
QTcF, CFB to On-Therapy10.3 ± 13.441.8 ± 10.82
QTcF, CFB to Test-of-Cure1.3 ± 12.093.6 ± 11.66
SecondaryChange From Baseline (CFB) in Vital Sign: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)

SBP and DBP were measured in a semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment with a non-missing value.

Time frame:
Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)
Reported as:
Mean · Millimeters of mercury (mmHg)
Change From Baseline (CFB) in Vital Sign: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Millimeters of mercury (mmHg)GepotidacinNitrofurantoin
Diastolic Blood Pressure, Baseline72.8 ± 11.9874.5 ± 12.60
Diastolic Blood Pressure, CFB to On-Therapy-2.6 ± 9.45-2.1 ± 9.36
Diastolic Blood Pressure, CFB to Test-of-Cure-2.4 ± 9.76-3.9 ± 9.64
Systolic Blood Pressure, Baseline118.2 ± 18.10118.7 ± 18.38
Systolic Blood Pressure, CFB to On-Therapy-3.1 ± 12.20-3.3 ± 13.32
Systolic Blood Pressure, CFB to Test-of-Cure-3.7 ± 11.63-4.1 ± 11.35
SecondaryChange From Baseline (CFB) in Vital Sign: Temperature

Temperature was measured in a semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment with a non-missing value.

Time frame:
Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)
Reported as:
Mean · Celsius
Change From Baseline (CFB) in Vital Sign: Temperature
CelsiusGepotidacinNitrofurantoin
Baseline36.49 ± 0.36736.44 ± 0.365
CFB to On-Therapy-0.05 ± 0.453-0.03 ± 0.425
CFB to Test-of-Cure-0.07 ± 0.397-0.02 ± 0.396
SecondaryChange From Baseline (CFB) in Vital Sign: Pulse Rate

Pulse rate was measured in a semi-supine position after 5 minutes rest. Baseline is defined as the latest pre-dose assessment with a non-missing value.

Time frame:
Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)
Reported as:
Mean · beats/minute
Change From Baseline (CFB) in Vital Sign: Pulse Rate
beats/minuteGepotidacinNitrofurantoin
Baseline69.7 ± 10.7972.2 ± 10.65
CFB to On-Therapy2.4 ± 10.361.4 ± 10.66
CFB to Test-of-Cure0.4 ± 9.30-0.5 ± 11.54
SecondaryPlasma Concentrations of Gepotidacin

Blood samples were collected for plasma concentration of Gepotidacin.

Time frame:
Baseline (Day 1 at 0-2h & >2h Post dose), Day 2 to 5 at Pre-dose, 0-2h & >2h Post Dose
Reported as:
Mean · Nanogram/ milliliter (ng/mL)
Plasma Concentrations of Gepotidacin
Nanogram/ milliliter (ng/mL)Gepotidacin
Baseline, POST-DOSE, Day 1, 0-2h5210.23 ± 3428.432
Baseline, POST-DOSE, Day 1, >2h5251.54 ± 2097.649
On-Therapy, PRE-DOSE, Day 2-5, pre-dose1960.14 ± 16752.767
On-Therapy, POST-DOSE, Day 2-5, 0-2h17548.67 ± 124724.240
On-Therapy, POST-DOSE, Day 2-5, >2h5976.40 ± 5142.635
SecondaryUrine Concentrations of Gepotidacin

Urine samples were collected for urine concentration of Gepotidacin.

Time frame:
Baseline (Day 1 at 0-2h & >2h Post dose), Day 2 to 5 at Pre-dose, 0-2h & >2h Post Dose
Reported as:
Mean · Microgram/ milliliter (ug/mL)
Urine Concentrations of Gepotidacin
Microgram/ milliliter (ug/mL)Gepotidacin
Baseline, POST-DOSE, Day 1, 0-2h506.988 ± 914.3140
Baseline, POST-DOSE, Day 1, >2h600.729 ± 644.2265
On-Therapy, PRE-DOSE, Day 2-5, pre-dose492.096 ± 565.8822
On-Therapy, POST-DOSE, Day 2-5, 0-2h901.554 ± 1451.8781
On-Therapy, POST-DOSE, Day 2-5, >2h1138.900 ± 1429.7998
SecondaryChange From Baseline (CFB) in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets at On Therapy and Test of Cure Visit

Blood samples were collected for the analysis of hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, and platelets. Baseline is defined as the latest pre-dose assessment with a non-missing value.

Time frame:
Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)
Reported as:
Mean · Giga cells per Liter (10^9 cells/L)
Change From Baseline (CFB) in Hematology Parameters - Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, and Platelets at On Therapy and Test of Cure Visit
Giga cells per Liter (10^9 cells/L)GepotidacinNitrofurantoin
Basophils, Baseline0.050 ± 0.02380.051 ± 0.0223
Basophils, CFB to On-Therapy-0.004 ± 0.0194-0.001 ± 0.0152
Basophils, CFB to Test-of-Cure-0.001 ± 0.0192-0.002 ± 0.0135
Eosinophils, Baseline0.134 ± 0.11990.121 ± 0.0977
Eosinophils, CFB to On-Therapy0.008 ± 0.05670.011 ± 0.0500
Eosinophils, CFB to Test-of-Cure0.028 ± 0.08620.023 ± 0.0630
Lymphocytes, Baseline1.657 ± 0.50011.727 ± 0.5203
Lymphocytes, CFB to On-Therapy-0.044 ± 0.39580.075 ± 0.4024
Lymphocytes, CFB to Test-of-Cure-0.054 ± 0.46980.111 ± 0.4414
Monocytes, Baseline0.388 ± 0.14740.375 ± 0.1394
Monocytes, CFB to On-Therapy-0.057 ± 0.1457-0.059 ± 0.1584
Monocytes, CFB to Test-of-Cure-0.049 ± 0.1503-0.033 ± 0.1393
Neutrophils, Baseline4.805 ± 2.11024.684 ± 2.0992
Neutrophils, CFB to On-Therapy-1.530 ± 1.8841-1.477 ± 1.9168
Neutrophils, CFB to Test-of-Cure-1.713 ± 2.2275-1.493 ± 2.1633
Platelets, Baseline261.0 ± 58.37253.6 ± 56.80
Platelets, CFB to On-Therapy5.7 ± 25.422.6 ± 21.53
Platelets, CFB to Test-of-Cure3.3 ± 34.804.2 ± 37.13
SecondaryChange From Baseline (CFB) in Hematology Parameter-Hemoglobin Level at On Therapy and Test of Cure Visit

Blood samples were collected for the analysis of hemoglobin level. Baseline is defined as the latest pre-dose assessment with a non-missing value

Time frame:
Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)
Reported as:
Mean · Grams per Liter (g/L)
Change From Baseline (CFB) in Hematology Parameter-Hemoglobin Level at On Therapy and Test of Cure Visit
Grams per Liter (g/L)GepotidacinNitrofurantoin
Baseline128.6 ± 10.70128.0 ± 10.91
CFB to On-Therapy-1.3 ± 6.01-1.0 ± 5.61
CFB to Test-of-Cure-2.3 ± 6.22-2.9 ± 6.39
SecondaryChange From Baseline (CFB) in Hematology Parameter- Hematocrit Level at On Therapy and Test of Cure Visit

Blood samples were collected for the analysis of hematocrit level. Baseline is defined as the latest pre-dose assessment with a non-missing value.

Time frame:
Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)
Reported as:
Mean · Proportion of red blood cells in blood
Change From Baseline (CFB) in Hematology Parameter- Hematocrit Level at On Therapy and Test of Cure Visit
Proportion of red blood cells in bloodGepotidacinNitrofurantoin
Baseline0.4355 ± 0.042420.4308 ± 0.05058
CFB to On-Therapy-0.0047 ± 0.032520.0067 ± 0.03567
CFB to Test-of-Cure-0.0082 ± 0.03441-0.0038 ± 0.03533
SecondaryChange From Baseline (CFB) in Hematology Parameter- Erythrocytes Count at On Therapy and Test of Cure Visit

Blood samples were collected for the analysis of erythrocytes count. Baseline is defined as the latest pre-dose assessment with a non-missing value.

Time frame:
Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)
Reported as:
Mean · Tera cells per Liter (10^12 cells/L)
Change From Baseline (CFB) in Hematology Parameter- Erythrocytes Count at On Therapy and Test of Cure Visit
Tera cells per Liter (10^12 cells/L)GepotidacinNitrofurantoin
Baseline4.302 ± 0.36504.245 ± 0.3758
CFB to On-Therapy-0.040 ± 0.2021-0.025 ± 0.1887
CFB to Test-of-Cure-0.085 ± 0.2157-0.098 ± 0.2218
SecondaryChange From Baseline (CFB) in Hematology Parameter - Mean Corpuscular Hemoglobin (MCH) at On Therapy and Test of Cure Visit

Blood samples were collected for the analysis of MCH. Baseline is defined as the latest pre-dose assessment with a non-missing value.

Time frame:
Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)
Reported as:
Mean · Picogram (pg)
Change From Baseline (CFB) in Hematology Parameter - Mean Corpuscular Hemoglobin (MCH) at On Therapy and Test of Cure Visit
Picogram (pg)GepotidacinNitrofurantoin
Baseline29.97 ± 2.06230.26 ± 2.170
CFB to On-Therapy-0.03 ± 0.536-0.05 ± 0.519
CFB to Test-of-Cure0.04 ± 0.6130.00 ± 0.629
SecondaryChange From Baseline (CFB) in Hematology Parameter - Mean Corpuscular Volume (MCV) at On Therapy and Test of Cure Visit

Blood samples were collected for the analysis of MCV. Baseline is defined as the latest pre-dose assessment with a non-missing value.

Time frame:
Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)
Reported as:
Mean · Femtoliter (fL)
Change From Baseline (CFB) in Hematology Parameter - Mean Corpuscular Volume (MCV) at On Therapy and Test of Cure Visit
Femtoliter (fL)GepotidacinNitrofurantoin
Baseline101.48 ± 8.607101.65 ± 10.185
CFB to On-Therapy-0.16 ± 6.3002.40 ± 7.634
CFB to Test-of-Cure0.08 ± 6.7401.61 ± 7.071
SecondaryChange From Baseline (CFB) in Clinical Chemistry Parameters - Calcium, Glucose, Potassium, Magnesium, Phosphate, Sodium, and Urea Nitrogen Levels at On Therapy and Test of Cure Visit

Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.

Time frame:
Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)
Reported as:
Mean · millimoles per liter (mmol/L)
Change From Baseline (CFB) in Clinical Chemistry Parameters - Calcium, Glucose, Potassium, Magnesium, Phosphate, Sodium, and Urea Nitrogen Levels at On Therapy and Test of Cure Visit
millimoles per liter (mmol/L)GepotidacinNitrofurantoin
Calcium, Baseline2.319018 ± 0.08169802.314716 ± 0.0868299
Calcium, CFB to On-Therapy-0.004536 ± 0.0766926-0.012341 ± 0.0695672
Calcium, CFB to Test-of-Cure-0.032315 ± 0.0855497-0.029885 ± 0.0860459
Glucose, Baseline5.196605 ± 1.13519795.458483 ± 1.7589320
Glucose, CFB to On-Therapy0.248377 ± 1.35757800.423189 ± 1.3092369
Glucose, CFB to Test-of-Cure0.057763 ± 1.15078510.156160 ± 1.2016889
Potassium, Baseline4.13 ± 0.3394.16 ± 0.364
Potassium, CFB to On-Therapy0.05 ± 0.3290.02 ± 0.310
Potassium, CFB to Test-of-Cure0.00 ± 0.3650.04 ± 0.370
Magnesium, Baseline0.862 ± 0.06050.860 ± 0.0632
Magnesium, CFB to On-Therapy-0.004 ± 0.0555-0.010 ± 0.0519
Magnesium, CFB to Test-of-Cure-0.010 ± 0.0569-0.014 ± 0.0651
Phosphate, Baseline1.184963 ± 0.15937571.206882 ± 0.1775576
Phosphate, CFB to On-Therapy0.009746 ± 0.1600765-0.031943 ± 0.1706300
Phosphate, CFB to Test-of-Cure0.019541 ± 0.17367310.036903 ± 0.1985578
Sodium, Baseline139.8 ± 2.25139.8 ± 2.13
Sodium, CFB to On-Therapy0.1 ± 2.33-0.2 ± 2.38
Sodium, CFB to Test-of-Cure0.1 ± 2.520.2 ± 2.42
Urea Nitrogen, Baseline4.3094 ± 1.322174.4145 ± 1.33139
Urea Nitrogen, CFB to On-Therapy-0.0948 ± 0.98541-0.1689 ± 0.85458
Urea Nitrogen, CFB to Test-of-Cure0.1423 ± 1.077800.1177 ± 0.91259
SecondaryChange From Baseline (CFB) in Clinical Chemistry Parameters - Serum Chloride at On Therapy and Test of Cure Visit

Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value

Time frame:
Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)
Reported as:
Mean · Milliequivalents per liter (mEq/L)
Change From Baseline (CFB) in Clinical Chemistry Parameters - Serum Chloride at On Therapy and Test of Cure Visit
Milliequivalents per liter (mEq/L)GepotidacinNitrofurantoin
Baseline102.3 ± 2.21102.4 ± 2.38
CFB to On-Therapy0.8 ± 2.230.3 ± 2.36
CFB to Test-of-Cure1.0 ± 2.460.6 ± 2.58
SecondaryChange From Baseline (CFB) in Clinical Chemistry Parameters - Direct Bilirubin, Total Bilirubin and Creatinine Levels at On Therapy and Test of Cure Visit

Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.

Time frame:
Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)
Reported as:
Mean · micromoles per Liter (umol/L)
Change From Baseline (CFB) in Clinical Chemistry Parameters - Direct Bilirubin, Total Bilirubin and Creatinine Levels at On Therapy and Test of Cure Visit
micromoles per Liter (umol/L)GepotidacinNitrofurantoin
Direct Bilirubin, Baseline3.4498 ± 0.238453.4329 ± 0.10767
Direct Bilirubin, CFB to On-Therapy-0.0056 ± 0.24374-0.0129 ± 0.10767
Direct Bilirubin, CFB to Test-of-Cure-0.0063 ± 0.20804-0.0113 ± 0.11053
Total Bilirubin, Baseline7.0731 ± 4.661026.0420 ± 3.11713
Total Bilirubin, CFB to On-Therapy-0.4079 ± 4.143170.3163 ± 3.23527
Total Bilirubin, CFB to Test-of-Cure-0.1723 ± 4.231820.2988 ± 2.99514
Creatinine, Baseline50.964 ± 8.752752.280 ± 11.9212
Creatinine, CFB to On-Therapy3.632 ± 6.6395-1.426 ± 6.9325
Creatinine, CFB to Test-of-Cure0.620 ± 7.90070.000 ± 7.0965
SecondaryChange From Baseline (CFB) in Clinical Chemistry Parameters - Creatinine Clearance at On Therapy and Test of Cure Visit

Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.

Time frame:
Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)
Reported as:
Mean · Milliliter/second (mL/s)
Change From Baseline (CFB) in Clinical Chemistry Parameters - Creatinine Clearance at On Therapy and Test of Cure Visit
Milliliter/second (mL/s)GepotidacinNitrofurantoin
Baseline1.8346749 ± 0.581998421.8690338 ± 0.63944090
CFB to On-Therapy-0.1155781 ± 0.278380720.0331548 ± 0.28390850
CFB to Test-of-Cure-0.0284139 ± 0.27653678-0.0111724 ± 0.24923906
SecondaryChange From Baseline (CFB) in Clinical Chemistry Parameters - Albumin and Protein Levels at On Therapy and Test of Cure Visit

Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.

Time frame:
Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)
Reported as:
Mean · gram per Liter (g/L)
Change From Baseline (CFB) in Clinical Chemistry Parameters - Albumin and Protein Levels at On Therapy and Test of Cure Visit
gram per Liter (g/L)GepotidacinNitrofurantoin
Albumin, Baseline44.7 ± 2.5144.1 ± 2.91
Albumin, CFB to On-Therapy-0.4 ± 2.19-0.3 ± 2.11
Albumin, CFB to Test-of-Cure-1.3 ± 2.36-1.2 ± 2.26
Protein, Baseline70.6 ± 4.1870.7 ± 4.46
Protein, CFB to On-Therapy-0.8 ± 3.50-0.7 ± 3.71
Protein, CFB to Test-of-Cure-2.1 ± 3.80-2.3 ± 3.72
SecondaryChange From Baseline (CFB) in Clinical Chemistry Parameters - Alkaline Phosphatase (ALP) and Alanine Aminotransferase (ALT) Levels at On Therapy and Test of Cure Visit

Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.

Time frame:
Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)
Reported as:
Mean · International Units per Liter (IU/L)
Change From Baseline (CFB) in Clinical Chemistry Parameters - Alkaline Phosphatase (ALP) and Alanine Aminotransferase (ALT) Levels at On Therapy and Test of Cure Visit
International Units per Liter (IU/L)GepotidacinNitrofurantoin
ALP, Baseline68.9 ± 22.0968.4 ± 22.18
ALP, CFB to On-Therapy-0.1 ± 6.10-0.4 ± 8.10
ALP, CFB to Test-of-Cure-2.9 ± 7.12-3.1 ± 9.28
ALT, Baseline17.0 ± 16.8016.7 ± 11.11
ALT, CFB to On-Therapy1.2 ± 6.16-0.2 ± 3.28
ALT, CFB to Test-of-Cure0.6 ± 12.59-1.1 ± 5.98
SecondaryChange From Baseline (CFB) in Clinical Chemistry Parameter - Aspartate Aminotransferase (AST) Levels at On Therapy and Test of Cure Visit

Blood samples were collected for the analysis of clinical chemistry parameters. Baseline is defined as the latest pre-dose assessment with a non-missing value.

Time frame:
Baseline (Day 1), On-Therapy (Days 2 to 5), and at TOC visit (Days 9 to 16)
Reported as:
Mean · Units per Liter (U/L)
Change From Baseline (CFB) in Clinical Chemistry Parameter - Aspartate Aminotransferase (AST) Levels at On Therapy and Test of Cure Visit
Units per Liter (U/L)GepotidacinNitrofurantoin
Baseline20.1 ± 17.2618.7 ± 7.12
CFB to On-Therapy0.4 ± 11.280.0 ± 3.85
CFB to Test-of-Cure0.8 ± 16.01-0.2 ± 4.49

Adverse events

Collected over All cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected from first dose (Day 1) to follow-up visit (Days 21 to 31).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Gepotidacin0/281 (0%)2/281 (0.7%)174/281 (61.9%)
Nitrofurantoin0/93 (0%)0/93 (0%)8/93 (8.6%)
Most frequent serious events
Most frequent serious events
EventGepotidacinNitrofurantoin
DiarrhoeaGastrointestinal disorders1/2810/93
VomitingGastrointestinal disorders1/2810/93
Clostridium difficile infectionInfections and infestations1/2810/93
Most frequent other events
Most frequent other events
EventGepotidacinNitrofurantoin
DiarrhoeaGastrointestinal disorders167/2817/93
NauseaGastrointestinal disorders35/2812/93

Baseline characteristics

ITT population: All participants (except for 6 participants from the site with GCP violation) were randomly assigned to the study treatment.

Age, Continuous
Age, Continuous(YEARS)GepotidacinNitrofurantoinTotal
Mean44.9 ± 18.7846.4 ± 19.2145.2 ± 18.88
Sex: Female, Male
Sex: Female, Male(Participants)GepotidacinNitrofurantoinTotal
Female28193374
Male000
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)GepotidacinNitrofurantoinTotal
Hispanic or Latino000
Not Hispanic or Latino28193374
Unknown or Not Reported000
07

Study locations

27 sites
  • GSK Investigational Site
    Chiba, 263-0043, Japan
  • GSK Investigational Site
    Chiba, 270-0034, Japan
  • GSK Investigational Site
    Chiba, 272-0107, Japan
  • GSK Investigational Site
    Chiba, 286-0201, Japan
  • GSK Investigational Site
    Fukuoka, 810-0001, Japan
  • GSK Investigational Site
    Fukuoka, 811-0120, Japan
  • GSK Investigational Site
    Fukuoka, 814-0013, Japan
  • GSK Investigational Site
    Fukuoka, 816-0943, Japan
  • GSK Investigational Site
    Gunma, 370-0826, Japan
  • GSK Investigational Site
    Hokkaido, 006-0816, Japan
  • GSK Investigational Site
    Ibaraki, 300-0062, Japan
  • GSK Investigational Site
    Ibaraki, 305-0821, Japan
  • GSK Investigational Site
    Kagoshima, 890-0073, Japan
  • GSK Investigational Site
    Kanagawa, 231-0861, Japan
  • GSK Investigational Site
    Kanagawa, 232-0067, Japan
  • GSK Investigational Site
    Kochi, 781-0085, Japan
  • GSK Investigational Site
    Miyagi, 980-0803, Japan
  • GSK Investigational Site
    Osaka, 534-0024, Japan
  • GSK Investigational Site
    Osaka, 564-0063, Japan
  • GSK Investigational Site
    Saga, 840-0831, Japan
  • GSK Investigational Site
    Saitama, 352-0001, Japan
  • GSK Investigational Site
    Saitama, 360-0012, Japan
  • GSK Investigational Site
    Tokyo, 130-0026, Japan
  • GSK Investigational Site
    Tokyo, 162-0804, Japan
  • GSK Investigational Site
    Tokyo, 167-0051, Japan
  • GSK Investigational Site
    Tokyo, 175-0093, Japan
  • GSK Investigational Site
    Tokyo, 186-0002, Japan
08

References and documents

Study documents

  • Study protocol · Nov 7, 2022
  • Statistical analysis plan · Apr 2, 2024

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

Individual participant data

Plan to share: Yes — Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

Supporting information: Study protocol, Sap, Icf, Csr

09

Registry details

Key details

Study ID
NCT05630833
Lead sponsor
GlaxoSmithKline
Responsible party
Sponsor
First posted
Nov 30, 2022
Start date
Jan 11, 2023
Primary completion
Feb 2, 2024
Completion
Feb 2, 2024
Results posted
Mar 17, 2025
Last update
Mar 17, 2025

Study contacts

GSK Clinical Trials
study director · GlaxoSmithKline

Oversight

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

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