Comparative Study to Evaluate Efficacy and Safety of Gepotidacin to Nitrofurantoin in Treatment of Uncomplicated Urinary Tract Infection (UTI)

• Status: Recruiting
• Trial end date: 2023-01-13
• Target enrollment: 0
• Participant gender: Female

Summary

Urinary tract infections (UTIs; acute cystitis) are very common, with approximately 11 percentage of women (>18 years of age) reporting at least 1 episode of acute cystitis per year. The purpose of this study to evaluate the therapeutic response (combined microbiological and clinical efficacy per participant) of oral gepotidacin compared to oral nitrofurantoin for acute cystitis in adolescent and adult female participants. In this study, participants will be randomly assigned in a 1:1 ratio to receive either oral gepotidacin or oral nitrofurantoin. The study will enroll approximately 2000 participants with uncomplicated UTI. The duration of the study will be approximately 28 days with 4 planned study visits.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline
• Treatments: Nitrofurantoin

Criteria

Inclusion Criteria:

• The participant is >=12 years of age at the time of signing the informed consent/assent and has a body weight >=40 kilogram (kg).

• The participant has 2 or more of the following clinical signs and symptoms of acute cystitis with onset <=72 hours prior to study entry: dysuria, frequency, urgency, or lower abdominal pain

• The participant has nitrite or pyuria (>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 female.

• Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

• A female participant is eligible to participate if she is a woman of childbearing potential (WOCBP) who is not pregnant as confirmed by a high sensitivity urine pregnancy test at Baseline (Day 1) regardless of current or prior contraception use or abstinence, is not breastfeeding, or is not a WOCBP.

• Additional requirements for pregnancy testing during and after study intervention are specified.

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

• The participant is capable of giving signed informed consent/assent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF)/assent form and protocol.

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 high blood pressure or uncontrolled diabetes.

• The participant has a history of sensitivity to the study interventions, 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 participant is immunocompromised or has altered immune defenses that may predispose the participant to a higher risk of treatment failure and/or complications (e.g., uncontrolled diabetes, renal transplant recipients, participants with clinically significant persistent granulocytopenia [absolute neutrophil count <1000/microliter (μL)], and participants receiving immunosuppressive therapy, including corticosteroid therapy [>40 milligrams (mg)/day prednisolone or equivalent for >1 week, >=20 mg/day prednisolone or equivalent for >2 weeks, or prednisolone or equivalent >=10 mg/day for >6 weeks]). Participants with a known cluster of differentiation 4 (CD4) count of <200 cells per cubic millimeter (cells/mm^3) should not be enrolled.

• The participant has any of the following: Medical condition that requires medication that may be impacted by inhibition of acetylcholinesterase, such as;

• Medical condition that requires medication that may be impacted by inhibition of acetylcholinesterase, such as:

• Poorly controlled asthma or chronic obstructive pulmonary disease at Baseline and, in the opinion of the investigator, not stable on current therapy

• Acute severe pain, uncontrolled with conventional medical management

• 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

• Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study intervention (e.g., ileostomy or malabsorption syndrome)

• The participant has a known glucose-6 phosphate dehydrogenase deficiency.

• The participant has a serious underlying disease that could be imminently life threatening, or the participant is unlikely to survive for the duration of the study period.

• The participant 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) 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.

• 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 vesico-ureteral 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 >=101 degree Fahrenheit, 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 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 or a strong P-glycoprotein (P-gp) inhibitor.

• For any participant >=12 to <18 years of age, the participant has an abnormal ECG reading at Baseline or during the study intervention.

• 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 ALT value >2 × upper limit of normal (ULN).

• The participant has a known bilirubin value >1.5 × ULN (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

• 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.

• The participant must agree not to use the medications or nondrug therapies from the Baseline Visit through the TOC Visit

• The participant has been previously enrolled in this study or has previously been treated with gepotidacin.

• The participant has participated in a clinical trial and has received an investigational product within 30 days or 5 half-lives, whichever is longer.