Comparative Study to Evaluate Efficacy and Safety of Gepotidacin to Nitrofurantoin in 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 at a unit dose strength of 750mg. Participants will administer two 750 mg tablets, BID. Each dose will be taken with water after consumption of food.; Placebo matching nitrofurantoin will be available as over-encapsulated unit-dose capsules. Participants will administer 1 capsule BID. Each dose should be taken with water after consumption of food.; Nitrofurantoin will be available as over-encapsulated 100 mg capsules containing 25 mg nitrofurantoin macrocrystals and 75 mg nitrofurantoin. Participants will administer one 100 mg capsule, BID. 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. Participants will administer two tablets, BID. 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: 1606.0
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:

          -  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 <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 female.

          -  The participant is capable of giving signed informed consent/assent.

        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 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 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:

               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 intervention
                  .

          -  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 Enterobacterales (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 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 (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).

          -  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 >=101.4 degree Fahrenheit (>=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 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.

          -  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 times upper limit of normal (ULN).

          -  The 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
             [%]).

          -  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.