A Study Evaluating Efficacy and Safety of Gepotidacin Compared With Ceftriaxone Plus Azithromycin in the Treatment of Uncomplicated Urogenital Gonorrhea

Study Overview
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Brief Summary
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This is a phase III, randomized, multicenter, open-label study which will be performed to evaluate efficacy and safety of oral Gepotidacin compared to intramuscular (IM) ceftriaxone plus oral azithromycin for the treatment of uncomplicated urogenital infection caused by Neisseria gonorrhoeae (N. gonorrhoeae) in adolescent and adult participants. In this study, participants will be randomly assigned to receive either oral gepotidacin or IM ceftriaxone plus oral azithromycin.

Official Title
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A Phase III, Randomized, Multicenter, Open-Label Study in Adolescent and Adult Participants Comparing the Efficacy and Safety of Gepotidacin to Ceftriaxone Plus Azithromycin in the Treatment of Uncomplicated Urogenital Gonorrhea Caused by Neisseria Gonorrhoeae

Conditions
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Gonorrhea

Intervention / Treatment
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* Drug: Gepotidacin
* Drug: Ceftriaxone
* Drug: Azithromycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be >=12 years of age at the time of signing the informed consent. Participants having body weight of >45 kilogram (kg). Participants having clinical suspicion of a urogenital gonococcal infection with or without pharyngeal and/or rectal gonococcal infection and have one of the following: male participants with purulent yellow, green, or white urethral discharge or female participants with abnormal cervical or vaginal mucopurulent discharge upon physical examination; or a prior positive culture for N. gonorrhoeae from up to 5 days before screening (as long as the participant has not received any treatment for this infection); or a Gram or equivalent stain (urogenital specimens only) positive or presumptive for Gram-negative intracellular diplococci from up to 5 days before screening (as long as the participant has not received any treatment for this infection); or a prior positive nucleic acid amplification test assay for N. gonorrhoeae from up to 7 days before screening (as long as the participant has not received any treatment for this infection). Participants 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 participants having his or her original urogenital anatomy at birth. Male participant must agree to use contraception (male condoms) during intercourse from the Baseline Visit through completion of the TOC Visit. Female participant 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. Participants 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 participants with a current diagnosis of epididymitis and/or orchitis at the time of the Baseline Visit. Participant 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. Participant 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. Participant 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. Participant is immunocompromised or has altered immune defenses that may predispose the participant to a higher risk of treatment failure and/or complications. Participants with a known cluster of differentiation 4 (CD4) count of <200 cells per cubic millimeter (cells/mm^3). Participant has any of the following: poorly controlled asthma or chronic obstructive pulmonary disease, 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 or participant has any surgical or medical condition that may interfere with drug absorption, distribution, metabolism, or excretion of the study treatment. Participant 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). Participant in the judgment of the investigator, would not be able or willing to comply with the protocol or complete study follow-up. 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 congenital long QT syndrome or known prolongation of corrected QT interval (QTc). 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 bradyarrhythmia 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 his or 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-glycoprotein (P-gp) inhibitor. For any participant >=12 to <18 years, the participant has an abnormal electrocardiogram (ECG) reading. The 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 history of cholestatic jaundice or hepatic dysfunction associated with prior use of azithromycin. 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%). 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 been previously randomized in this study or has previously been treated with Gepotidacin. Participant has participated in a clinical trial and has received an investigational product within 30 days or 5 half-lives, whichever is longer. Participant 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. Participant has received any antibacterial therapy for the treatment of a gonococcal infection within 14 days before the Baseline Visit. Participant has received any systemic, topical, or intravaginal antibiotics or any systemic antifungals within 7 days before the Baseline Visit. Participant must not use St John's wort or ergot derivatives from within 14 days before the Baseline Visit through the TOC Visit.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants receiving Gepotidacin<br>Participants 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 10 to 12 hours after the first dose. | Drug: Gepotidacin<br>* 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.<br>|
| Active Comparator: Participants receiving Ceftriaxone plus Azithromycin<br>Participants 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. | Drug: Ceftriaxone<br>* Ceftriaxone is available as sterile powder for reconstitution. It will be administered as one 500-mg IM dose at the study site.<br>Drug: Azithromycin<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with culture-confirmed bacterial eradication of Neisseria gonorrhoeae from the urogenital site at the Test-of-Cure (TOC) | Pre-treatment urogenital swab specimen will be obtained for bacteriological culture for N. gonorrhoeae. Test-of-Cure is defined by urogenital site as culture-confirmed bacterial eradication of N. gonorrhoeae observed 4 to 8 days post-treatment. | From Day 4 to Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with culture-confirmed bacterial eradication of Neisseria gonorrhoeae from the rectal site at the TOC | Pre-treatment rectal swab specimen will be obtained for bacteriological culture for N. gonorrhoeae. Test-of-Cure is defined by rectal site as culture-confirmed bacterial eradication of N. gonorrhoeae observed 4 to 8 days post-treatment. | From Day 4 to Day 8 | 
| Number of participants with culture-confirmed bacterial eradication of Neisseria gonorrhoeae from the pharyngeal site at the TOC | 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 4 to 8 days post-treatment | From Day 4 to Day 8 | 
| Number of participants with treatment-emergent adverse events and serious adverse events (SAEs) | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, 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. | Up to Day 21 | 
| Change from Baseline in neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count and platelet count (Giga cells per liter) | Blood samples will be collected for the assessment of neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count and platelet count. | Baseline (Day 1) and from Day 4 to Day 8 | 
| Change from Baseline in hemoglobin level (Grams per Liter) | Blood samples will be collected for the assessment of hemoglobin level. | Baseline (Day 1) and from Day 4 to Day 8 | 
| Change from Baseline in hematocrit level (Proportion of red blood cells in blood) | Blood samples will be collected for the assessment of hematocrit level. | Baseline (Day 1) and from Day 4 to Day 8 | 
| Change from Baseline in red blood cell (RBC) count (Trillion cells per liter) | Blood samples will be collected for the assessment of RBC count. | Baseline (Day 1) and from Day 4 to Day 8 | 
| Change from Baseline in mean corpuscular hemoglobin (MCH) (Picograms) | Blood samples will be collected for the assessment of MCH. | Baseline (Day 1) and from Day 4 to Day 8 | 
| Change from Baseline in mean corpuscular volume (MCV) (Femtoliters) | Blood samples will be collected for the assessment of MCV. | Baseline (Day 1) and from Day 4 to Day 8 | 
| Change from Baseline in blood urea nitrogen, glucose non-fasting, calcium, chloride, sodium, magnesium and potassium levels (Millimoles per Liter) | Blood samples will be collected for the assessment of blood urea nitrogen, glucose non-fasting, calcium, chloride, sodium, magnesium and potassium levels. | Baseline (Day 1) and from Day 4 to Day 8 | 
| Change from Baseline in total bilirubin, direct bilirubin and creatinine levels (Micromoles per liter) | Blood samples will be collected for the assessment of total bilirubin, direct bilirubin and creatinine levels. | Baseline (Day 1) and from Day 4 to Day 8 | 
| Change from Baseline in albumin and total protein levels (Grams per liter) | Blood samples will be collected for the assessment of albumin and total protein levels. | Baseline (Day 1) and from Day 4 to Day 8 | 
| Change from Baseline in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase levels (International units per Liter) | Blood samples will be collected for the assessment of AST, ALT and alkaline phosphatase levels. | Baseline (Day 1) and from Day 4 to Day 8 | 
| Number of participants with abnormal urinalysis Dipstick results | Urine samples will be collected to assess pH, glucose, protein, blood and ketones by Dipstick method. | From Day 4 to Day 8 | 
| Change from Baseline in specific gravity of urine (Ratio) | Urine samples will be collected for the measurement of specific gravity. | Baseline (Day 1) and from Day 4 to Day 8 | 
| Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) (Millimeters of mercury) | SBP and DBP will be assessed in the semi-supine position after 5 minutes rest. | Baseline (Day 1) and from Day 4 to Day 8 | 
| Change from Baseline in pulse rate (Beats per minute) | Pulse measurements will be assessed in the semi-supine position after 5 minutes rest. | Baseline (Day 1) and from Day 4 to Day 8 | 
| Change from Baseline in body temperature (Degrees Celsius) | Changes in body temperature from Baseline will be assessed. | Baseline (Day 1) and from Day 4 to Day 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urogenital Gonorrhea, Gepotidacin, Neisseria gonorrhoeae, Efficacy, Phase 3