• Number of subjects with culture-confirmed bacterial eradication of Neisseria gonorrhoeae from the rectal site at the TOC [ Time Frame: Up to Day 8 ]
  Pre-treatment rectal swab specimen will be obtained for bacteriological culture for N. gonorrhoea. Test-of-Cure is defined by rectal site as culture-confirmed bacterial eradication of N. gonorrhoea observed 3 to 7 days post-treatment.
• Number of subjects with culture-confirmed bacterial eradication of Neisseria gonorrhoeae from the pharyngeal site at the TOC [ Time Frame: Up to Day 8 ]
  Pre-treatment pharyngeal swab specimen will be obtained for bacteriological culture for N. gonorrhoea. Test-of-Cure is defined by pharyngeal site as culture-confirmed bacterial eradication of N. gonorrhoea observed 3 to 7 days post-treatment
• Number of subjects with treatment-emergent adverse events and serious adverse events (SAEs) [ Time Frame: Up to Day 21 ]
  An adverse event (AE) is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity, is a congenital anomaly or birth defect, any other situation that require medical or scientific judgment.
• Change from Baseline in neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count and platelet count [ Time Frame: Baseline and up to Day 8 ]
  Blood samples will be collected for the assessment of neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count and platelet count. All parameters have "Giga cells per Liter" as unit of measure.
• Change from Baseline in hemoglobin level [ Time Frame: Baseline and up to Day 8 ]
  Blood samples will be collected for the assessment of hemoglobin level.
• Change from Baseline in hematocrit level [ Time Frame: Baseline and up to Day 8 ]
  Blood samples will be collected for the assessment of hematocrit level.
• Change from Baseline in red blood cell (RBC) count [ Time Frame: Baseline and up to Day 8 ]
  Blood samples will be collected for the assessment of RBC count.
• Change from Baseline in mean corpuscular hemoglobin (MCH) [ Time Frame: Baseline and up to Day 8 ]
  Blood samples will be collected for the assessment of MCH.
• Change from Baseline in mean corpuscular volume (MCV) [ Time Frame: Baseline and up to Day 8 ]
  Blood samples will be collected for the assessment of MCV.
• Change from Baseline in blood urea nitrogen, glucose non-fasting, calcium, chloride, sodium and potassium levels [ Time Frame: Baseline and up to Day 8 ]
  Blood samples will be collected for the assessment of blood urea nitrogen, glucose non-fasting, calcium, chloride, sodium and potassium levels. All parameters have "Millimole per Liter" as unit of measure.
• Change from Baseline in total bilirubin, direct bilirubin and creatinine levels [ Time Frame: Baseline and up to Day 8 ]
  Blood samples will be collected for the assessment of total bilirubin, direct bilirubin and creatinine levels. All parameters have "Micromoles per liter" as unit of measure.
• Change from Baseline in albumin and total protein levels [ Time Frame: Baseline and up to Day 8 ]
  Blood samples will be collected for the assessment of albumin and total protein levels. All parameters have "Gram per liter" as unit of measure.
• Change from Baseline in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase levels [ Time Frame: Baseline and up to Day 8 ]
  Blood samples will be collected for the assessment of AST, ALT and alkaline phosphatase levels. All parameters have "International units per Liter" as unit of measure.
• Number of subjects with abnormal urinalysis Dipstick results [ Time Frame: Up to Day 8 ]
  Urine samples will be collected to assess pH, glucose, protein, blood and ketones by Dipstick method.
• Change from Baseline in specific gravity of urine [ Time Frame: Baseline and up to Day 8 ]
  Urine samples will be collected for the measurement of specific gravity.
• Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) [ Time Frame: Baseline and up to Day 8 ]
  SBP and DBP will be assessed in the semi-supine position after 5 minutes rest.
• Change from Baseline in pulse rate [ Time Frame: Baseline and up to Day 8 ]
  Pulse measurements will be assessed in the semi-supine position after 5 minutes rest.
• Change from Baseline in body temperature [ Time Frame: Baseline and up to Day 8 ]
  Changes in body temperature from Baseline will be assessed.

• Drug: Gepotidacin
  Gepotidacin will be administered as 3000 milligram (mg) oral dose (4 X 750 mg tablets) at the study site followed by 3000 mg oral dose (4 X 750 mg tablets) as an outpatient. Each dose should be taken after food consumption and with water.
• Drug: Ceftriaxone
  Ceftriaxone is available as sterile powder for reconstitution. It will be administered as one 500-mg IM dose at the study site.
• Drug: Azithromycin
  Azithromycin will be administered as 1000 mg oral dose (2 X 500 mg tablets) at the study site. Dose should be taken after food consumption and with water.

• Active Comparator: Gepotidacin
  Subjects will receive Gepotidacin orally at the study site during the Baseline (Day 1) visit followed by self-administration of a second oral dose as an outpatient 6 to 12 hours after the first dose.
  Intervention: Drug: Gepotidacin
• Active Comparator: Ceftriaxone plus Azithromycin
  Subjects will receive a single IM dose of Ceftriaxone plus a single oral dose of Azithromycin at the study site during the Baseline (Day 1) visit.
  Interventions:

  • Drug: Ceftriaxone
  • Drug: Azithromycin

Inclusion Criteria:

• Subjects must be >=12 years of age at the time of signing the informed consent.
• Subjects having body weight of >45 kilogram (kg).
• Subjects having clinical suspicion of a urogenital gonococcal infection with or without pharyngeal and/or rectal gonococcal infection and have one of the following: a prior positive culture for Neisseria gonorrhoeae from up to 5 days before screening (as long as the subject has not received any treatment for this infection) or a Gram stain (urogenital specimens only) positive or presumptive for Gram-negative intracellular diplococci from up to 5 days before screening (as long as the subject has not received any treatment for this infection) or a prior positive nucleic acid amplification test assay for Neisseria gonorrhoeae from up to 7 days before screening (as long as the subject has not received any treatment for this infection).
• Subjects who are willing to avoid anal, oral, and vaginal sexual intercourse or use condoms for all forms of intercourse from the Baseline Visit through the TOC Visit.
• Male or female subjects having his or her original urogenital anatomy at birth.
• Male subject must agree to use contraception (male condoms) during intercourse from the Baseline Visit through completion of the TOC Visit.
• Female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) or WOCBP who agrees to follow the contraceptive guidance (male partners of WOCBP must use a male condom during intercourse) from the Baseline Visit through completion of the TOC Visit.
• Subjects who are capable of giving signed informed consent or assent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) or assent form and in study protocol.

Exclusion Criteria:

• Male subjects with a current diagnosis of epididymitis and/or orchitis at the time of the Baseline Visit.
• Subject who is suspected or confirmed to have a Chlamydia trachomatis infection and per the investigator's judgement standard-of-care treatment for this infection cannot be safely postponed until the TOC Visit.
• Subject has a body mass index >=40 kilogram per square meter (kg/m^2) or has a body mass index >=35.0 kg/m^2 and is experiencing obesity-related health conditions such as high blood pressure or diabetes.
• Subject has a history of sensitivity to the study treatments, or components thereof, or a history of a drug (including erythromycin and any macrolide or ketolide drug) or other allergy that, in the opinion of the investigator or medical monitor, contraindicates his or her participation.
• Subject is immunocompromised or has altered immune defenses that may predispose the subject to a higher risk of treatment failure and/or complications. For example, subjects with diabetes, renal transplant recipients, subjects with clinically significant persistent granulocytopenia (absolute neutrophil count <1000 per microliter [μL]) and subjects receiving immunosuppressive therapy, including corticosteroid therapy (>40 mg per day prednisolone or equivalent for >1 week, >=20 mg per day prednisolone or equivalent for >2 weeks, or prednisolone or equivalent >=10 mg per day for >6 weeks). Subjects with a known cluster of differentiation 4 (CD4) count of <200 cells per cubic millimeter (cells/mm^3) should not be enrolled.
• Subject has a medical condition that requires medication that may be impacted by inhibition of acetylcholinesterase, such as, poorly controlled asthma or chronic obstructive pulmonary disease at the Baseline Visit 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 subject has any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study treatment (For example., ileostomy or malabsorption syndrome).
• Subject has known anuria, oliguria, or severe impairment of renal function (creatinine clearance <30 milliliter per minute [mL/min] or clinically significant elevated serum creatinine as determined by the investigator).
• Subject in the judgment of the investigator, would not be able or willing to comply with the protocol or complete study follow-up.
• Subject has a serious underlying disease that could be imminently life threatening, or the subject is unlikely to survive for the duration of the study period.
• Subject has congenital long QT syndrome or known prolongation of corrected QT interval (QTc).
• Subject has uncompensated heart failure.
• Subject has severe left ventricular hypertrophy.
• Subject has a family history of QT prolongation or sudden death.
• Subject has a recent history of vasovagal syncope or episodes of symptomatic bradycardia or bradyarrhythmia within the last 12 months.
• With the exception of azithromycin study treatment, the subject 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 his or her Baseline Visit, which cannot be safely discontinued from the Baseline Visit to the TOC Visit; or the subject is taking a strong cytochrome P450 enzyme 3A4 (CYP3A4) inhibitor or a strong P-glycoprotein (P-gp) inhibitor.
• For any subject >=12 to <18 years, the subject has an abnormal electrocardiogram (ECG) reading.
• The subject has a QTc >450 millisecond (msec) or a QTc >480 msec for subjects with bundle-branch block.
• Subject has a documented or recent history of uncorrected hypokalemia within the past 3 months.
• Subject has a known history of cholestatic jaundice or hepatic dysfunction associated with prior use of azithromycin.
• Subject has a known alanine aminotransferase (ALT) value >2 times upper limit of normal (ULN).
• Subject 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%).
• Subject 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).
• Subject has been previously enrolled in this study or has previously been treated with Gepotidacin.
• Subject has participated in a clinical trial and has received an investigational product within 30 days or 5 half-lives, whichever is longer.
• Subject has any of the following gonococcal infections that require a different dose or duration of treatment: suspected or confirmed pelvic inflammatory disease or suspected or confirmed gonococcal arthritis or suspected or confirmed gonococcal conjunctivitis or suspected or confirmed gonococcal endocarditis or other evidence of disseminated gonococcal infection.
• Subject has received any antibacterial therapy for the treatment of a gonococcal infection within 14 days before the Baseline Visit.
• Subject has received any systemic, topical, or intravaginal antibiotics or any systemic antifungals within 7 days before the Baseline Visit.
• Subject must not use St John's wort or ergot derivatives from within 14 days before the Baseline Visit through the TOC Visit.