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

• ClinicalTrials.gov Identifier: NCT04010539
• Recruitment Status: Completed
• First Posted: July 8, 2019
• Last Update Posted: December 14, 2023
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Tracking Information

• First Submitted Date: July 2, 2019
• First Posted Date: July 8, 2019
• Last Update Posted Date: December 14, 2023
• Actual Study Start Date: October 21, 2019
• Actual Primary Completion Date: October 10, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 15, 2023)

Number of participants with culture-confirmed bacterial eradication of Neisseria gonorrhoeae from the urogenital site at the Test-of-Cure (TOC) [ Time Frame: From Day 4 to Day 8 ]

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.

Original Primary Outcome Measures (submitted: July 5, 2019)

Number of subjects with culture-confirmed bacterial eradication of Neisseria gonorrhoeae from the urogenital site at the Test-of-Cure (TOC) [ Time Frame: Up to Day 8 ]

Pre-treatment urogenital swab specimen will be obtained for bacteriological culture for N. gonorrhoea. Test-of-Cure is defined by urogenital site as culture-confirmed bacterial eradication of N. gonorrhoea observed 3 to 7 days post-treatment.

Current Secondary Outcome Measures (submitted: March 15, 2023)

• Number of participants with culture-confirmed bacterial eradication of Neisseria gonorrhoeae from the rectal site at the TOC [ Time Frame: From Day 4 to Day 8 ]
  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.
• Number of participants with culture-confirmed bacterial eradication of Neisseria gonorrhoeae from the pharyngeal site at the TOC [ Time Frame: From Day 4 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 4 to 8 days post-treatment
• Number of participants 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 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.
• Change from Baseline in neutrophil count, lymphocyte count, monocyte count, eosinophil count, basophil count and platelet count (Giga cells per liter) [ Time Frame: Baseline (Day 1) and from Day 4 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.
• Change from Baseline in hemoglobin level (Grams per Liter) [ Time Frame: Baseline (Day 1) and from Day 4 to Day 8 ]
  Blood samples will be collected for the assessment of hemoglobin level.
• Change from Baseline in hematocrit level (Proportion of red blood cells in blood) [ Time Frame: Baseline (Day 1) and from Day 4 to Day 8 ]
  Blood samples will be collected for the assessment of hematocrit level.
• Change from Baseline in red blood cell (RBC) count (Trillion cells per liter) [ Time Frame: Baseline (Day 1) and from Day 4 to Day 8 ]
  Blood samples will be collected for the assessment of RBC count.
• Change from Baseline in mean corpuscular hemoglobin (MCH) (Picograms) [ Time Frame: Baseline (Day 1) and from Day 4 to Day 8 ]
  Blood samples will be collected for the assessment of MCH.
• Change from Baseline in mean corpuscular volume (MCV) (Femtoliters) [ Time Frame: Baseline (Day 1) and from Day 4 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, magnesium and potassium levels (Millimoles per Liter) [ Time Frame: Baseline (Day 1) and from Day 4 to Day 8 ]
  Blood samples will be collected for the assessment of blood urea nitrogen, glucose non-fasting, calcium, chloride, sodium, magnesium and potassium levels.
• Change from Baseline in total bilirubin, direct bilirubin and creatinine levels (Micromoles per liter) [ Time Frame: Baseline (Day 1) and from Day 4 to Day 8 ]
  Blood samples will be collected for the assessment of total bilirubin, direct bilirubin and creatinine levels.
• Change from Baseline in albumin and total protein levels (Grams per liter) [ Time Frame: Baseline (Day 1) and from Day 4 to Day 8 ]
  Blood samples will be collected for the assessment of albumin and total protein levels.
• Change from Baseline in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase levels (International units per Liter) [ Time Frame: Baseline (Day 1) and from Day 4 to Day 8 ]
  Blood samples will be collected for the assessment of AST, ALT and alkaline phosphatase levels.
• Number of participants with abnormal urinalysis Dipstick results [ Time Frame: From Day 4 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 (Ratio) [ Time Frame: Baseline (Day 1) and from Day 4 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) (Millimeters of mercury) [ Time Frame: Baseline (Day 1) and from Day 4 to Day 8 ]
  SBP and DBP will be assessed in the semi-supine position after 5 minutes rest.
• Change from Baseline in pulse rate (Beats per minute) [ Time Frame: Baseline (Day 1) and from Day 4 to Day 8 ]
  Pulse measurements will be assessed in the semi-supine position after 5 minutes rest.
• Change from Baseline in body temperature (Degrees Celsius) [ Time Frame: Baseline (Day 1) and from Day 4 to Day 8 ]
  Changes in body temperature from Baseline will be assessed.

Original Secondary Outcome Measures (submitted: July 5, 2019)

• 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study Evaluating Efficacy and Safety of Gepotidacin Compared With Ceftriaxone Plus Azithromycin in the Treatment of Uncomplicated Urogenital Gonorrhea
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Gonorrhea

Intervention

• 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.

Study Arms

• Experimental: Participants receiving Gepotidacin
  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.
  Intervention: Drug: Gepotidacin
• Active Comparator: Participants receiving Ceftriaxone plus Azithromycin
  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.
  Interventions:

  • Drug: Ceftriaxone
  • Drug: Azithromycin

• Publications *: Fishman C, Caverly Rae JM, Posobiec LM, Laffan SB, Lerman SA, Pearson N, Janmohamed S, Dumont E, Nunn-Floyd D, Stanislaus DJ. Novel Bacterial Topoisomerase Inhibitor Gepotidacin Demonstrates Absence of Fluoroquinolone-Like Arthropathy in Juvenile Rats. Antimicrob Agents Chemother. 2022 Nov 15;66(11):e0048322. doi: 10.1128/aac.00483-22. Epub 2022 Oct 18.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 13, 2023): 628
• Original Estimated Enrollment (submitted: July 5, 2019): 600
• Actual Study Completion Date: October 10, 2023
• Actual Primary Completion Date: October 10, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Germany, Mexico, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04010539
• Other Study ID Numbers: 116577; 2018-001780-23 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: 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/
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: 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.
• Access Criteria: 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.
• URL: https://www.gsk.com/en-gb/innovation/trials/data-transparency/

• Current Responsible Party: GlaxoSmithKline
• Original Responsible Party: Same as current
• Current Study Sponsor: GlaxoSmithKline
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

• PRS Account: GlaxoSmithKline
• Verification Date: December 2023