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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 3

Conditions: Urinary Tract Infections

Treatments: Drug: Placebo matching gepotidacin; Drug: Gepotidacin; Drug: Nitrofurantoin; Drug: Placebo matching nitrofurantoin

Study type: Interventional

Funder types: Industry

Identifiers

NCT04187144

212390

2020-000553-27 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 1,606 patients

Sex: Female

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

1,606 participants in 2 patient groups

Gepotidacin

Experimental group

Description:

Participants will be administered oral doses of 1500 milligrams (mg) gepotidacin plus nitrofurantoin matching placebo BID; approximately every 12 hours for 5 days.

Treatment:

Drug: Gepotidacin

Drug: Placebo matching nitrofurantoin

Nitrofurantoin

Active Comparator group

Description:

Participants will be administered oral doses of 100 mg nitrofurantoin plus gepotidacin matching placebo BID; approximately every 12 hours for 5 days.

Treatment:

Drug: Nitrofurantoin

Drug: Placebo matching gepotidacin