The study will be conducted to evaluate the clinical symptom improvement and safety of oral gepotidacin for treatment of uncomplicated UTI (acute cystitis) in adolescent and adult female participants.

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).
• 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 (presence of 3 plus (+)/large leukocyte esterase) on a urine dipstick test from a pre-treatment clean-catch midstream urine sample.
• The participant is capable of giving signed informed consent/assent.
• The participant is female.

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 defences 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
• Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study intervention.
• 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 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 overactive bladder, chronic incontinence, or chronic interstitial cystitis, that may interfere with the clinical efficacy assessments or preclude complete resolution of uUTI 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 <30 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 torsade 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-gp inhibitor
• The participant has a mean triplicate QTc >450 msec or a mean triplicate 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 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).
• The participant has received treatment with other systemic antimicrobials or systemic antifungals within 1 week before study entry.
• The participant plans to use any of the prohibited medications or nondrug therapies from the Baseline Visit through 7 days after the first dose of study intervention.
• 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.

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/

Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.

Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.