A Study to Evaluate Efficacy and Safety of Gepotidacin in the Treatment of Uncomplicated Urinary Tract Infection (UTI)
Condition: Urinary Tract Infections
MeSH terms: Infections; Communicable Diseases; Urinary Tract Infections
Intervention: Gepotidacin; Placebo matching nitrofurantoin; Nitrofurantoin; Placebo matching gepotidacin
Intervention description: Gepotidacin will be available as tablets containing 750 mg gepotidacin. Each dose should be taken with water after consumption of food.; Placebo matching nitrofurantoin will be available as over-encapsulated unit-dose capsules. Each dose should be taken with water after consumption of food.; Nitrofurantoin will be available as over-encapsulated capsules containing 25 mg nitrofurantoin macrocrystals and 75 mg nitrofurantoin. Each dose should be taken with water after consumption of food.; Placebo matching gepotidacin will be available as unit-dose gepotidacin placebo-to-match tablet. Each dose should be taken with water after consumption of food.
Intervention MeSH terms: Nitrofurantoin; Gepotidacin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1531.0
Sex: Female
Minimum age: 12 Years
Healthy volunteers: No
Keywords: Acute cystitis; Efficacy; Gepotidacin; Nitrofurantoin; Urinary Tract Infection; Simple cystitis

Summary:

      The study will be conducted to evaluate the therapeutic response (combined per participant
      microbiological and clinical response) of oral gepotidacin compared to oral nitrofurantoin
      for treatment of uncomplicated UTI (acute cystitis) in adolescent and adult female
      participants.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants having >=12 years of age at the time of signing the informed
             consent/assent and have a body weight >=40 kilograms (kg).

          -  Participants having 2 or more of the following clinical signs and symptoms of acute
             cystitis with onset <96 hours prior to study entry: dysuria, frequency, urgency, or
             lower abdominal pain.

          -  Participants having nitrite or pyuria (greater than [>]15 white blood cells [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.

          -  Participant is capable of giving signed informed consent/assent.

        Exclusion Criteria:

          -  Participant resides in a nursing home or dependent care type-facility.

          -  Participant has a body mass index >=40.0 kilogram per square meter (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.

          -  Participant has a history of sensitivity to the study treatments, 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.

          -  Participant is immunocompromised or has altered immune defenses that may predispose
             the participant to a higher risk of treatment failure and/or complications.

          -  Participant has any of the following:

               1. Poorly controlled asthma or chronic obstructive pulmonary disease; acute severe
                  pain; active peptic ulcer disease; Parkinson disease; myasthenia gravis; Or

               2. Known acute porphyria.

               3. Any surgical or medical condition (active or chronic) that may interfere with
                  drug absorption, distribution, metabolism, or excretion of the study treatment.

          -  Participant has a known glucose-6-phosphate dehydrogenase deficiency.

          -  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.

          -  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 Enterobacterales (other than Escherichia coli) as the contributing
             pathogen.

          -  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.

          -  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 (for
             example [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).

          -  Participant has an indwelling catheter, nephrostomy, ureter stent, or other foreign
             material in the urinary tract.

          -  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 >=101.4 Degrees Fahrenheit (F) (>=38
             Degrees Celsius [C]), flank pain, chills, or any other manifestations suggestive of
             upper UTI.

          -  Participant has known anuria, oliguria, or significant impairment of renal function
             (creatinine clearance <60 milliliter per minute [mL/min] or clinically significant
             elevated serum creatinine as determined by the investigator).

          -  Participant presents with vaginal discharge at Baseline (e.g., suspected sexually
             transmitted disease).

          -  Participant has congenital long QT syndrome or known prolongation of the corrected QT
             (QTc) interval.

          -  Participant has uncompensated heart failure.

          -  Participant has severe left ventricular hypertrophy.

          -  Participant has a family history of QT prolongation or sudden death.

          -  Participant has a recent history of vasovagal syncope or episodes of symptomatic
             bradycardia or brady-arrhythmia within the last 12 months.

          -  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
             electrocardiogram (ECG) reading.

          -  Participant has a QTc >450 millisecond (msec) or a QTc >480 msec for participants with
             bundle-branch block.

          -  Participant has a documented or recent history of uncorrected hypokalemia within the
             past 3 months.

          -  Participant has a known alanine aminotransferase (ALT) value >2 times upper limit of
             normal (ULN).

          -  Participant 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 percent [%]).

          -  Participant 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).

          -  Participant has a previous history of cholestatic jaundice or hepatic dysfunction
             associated with nitrofurantoin.

          -  Participant has received treatment with other systemic antimicrobials or systemic
             antifungals within 1 week before study entry.