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

GlaxoSmithKline1 site in 1 country628 target enrollmentOctober 21, 2019

ConditionsGonorrhea

InterventionsGepotidacin Ceftriaxone Azithromycin

DrugsGepotidacin Ceftriaxone Azithromycin

Overview

Phase: Phase 3
Intervention: Gepotidacin
Conditions: Gonorrhea
Sponsor: GlaxoSmithKline
Enrollment: 628
Locations: 1
Primary Endpoint: Number of Participants With Culture-Confirmed Bacterial Eradication of Neisseria Gonorrhoeae (NG) From the Urogenital Site at the Test-Of-Cure (TOC) Visit (Day 4 to 8)
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

October 21, 2019

End Date

October 10, 2023

Last Updated

last year

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

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.

Arms & Interventions

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: Gepotidacin

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.

Intervention: Ceftriaxone

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.

Intervention: Azithromycin

Outcomes

Primary Outcomes

Number of Participants With Culture-Confirmed Bacterial Eradication of Neisseria Gonorrhoeae (NG) From the Urogenital Site at the Test-Of-Cure (TOC) Visit (Day 4 to 8)

Time Frame: Baseline (Day 1) and TOC visit (Day 4 to 8)

Urogenital specimens were obtained for bacteriological culture at the Baseline (Day 1) and TOC (Day 4 to 8) visits and were compared to determine microbiological outcome. Microbiological success was defined as culture-confirmed elimination of baseline pathogen (NG) from a bacteriology sample taken at the TOC visit without the participant receiving other systemic antimicrobials before this visit. Microbiological failure was categorized as "Bacterial Persistence (BP)" and "Unable to Determine (UTD)" outcomes. Bacterial persistence was defined as culture-confirmed persistence of baseline NG pathogen from a bacteriology sample taken at the TOC visit without the participant receiving other systemic antimicrobials before this visit. UTD was defined as inability to determine the TOC NG pathogen outcome (e.g., no bacteriological sample taken for culture, sample lost, visit did not occur etc.) or the participant received other systemic antimicrobials before the TOC visit.

Secondary Outcomes

Change From Baseline (CFB) in Hematology Parameters: Basophils, Eosinophil, Leukocytes, Neutrophils, Platelets, Lymphocytes, Monocytes, Neutrophils and Nucleated Erythrocytes(Baseline (Day 1) and TOC visit (Day 4 to 8))
Change From Baseline in Hematology Parameters: Mean Corpuscular Hemoglobin Concentration (MCHC) and Hemoglobin (Hb)(Baseline (Day 1) and TOC visit (Day 4 to 8))
Change From Baseline in Hematology Parameter: Hematocrit(Baseline (Day 1) and TOC visit (Day 4 to 8))
Change From Baseline in Hematology Parameter: Mean Corpuscular Volume (MCV)(Baseline (Day 1) and TOC visit (Day 4 to 8))
Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) and Any Serious Adverse Events (SAEs)(Up to 21 days)
Change From Baseline in Clinical Chemistry Parameters: Urea Nitrogen (UN), Glucose, Calcium, Chloride, Sodium, Magnesium and Potassium(Baseline (Day 1) and TOC visit (Day 4 to 8))
Change From Baseline in Clinical Chemistry Parameters: Bilirubin, Direct Bilirubin and Creatinine(Baseline (Day 1) and TOC visit (Day 4 to 8))
Number of Participants With Culture-Confirmed Bacterial Eradication of NG From the Rectal Site at the TOC Visit(Baseline (Day 1) and TOC visit (Day 4 to 8))
Number of Participants With Culture-Confirmed Bacterial Eradication of NG From the Pharyngeal Site at the TOC Visit(Baseline (Day 1) and TOC visit (Day 4 to 8))
Change From Baseline in Hematology Parameter: Erythrocytes(Baseline (Day 1) and TOC visit (Day 4 to 8))
Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin (MCH)(Baseline (Day 1) and TOC visit (Day 4 to 8))
Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein(Baseline (Day 1) and TOC visit (Day 4 to 8))
Change From Baseline in Clinical Chemistry Parameters: Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) and Alkaline Phosphatase (ALP)(Baseline (Day 1) and TOC visit (Day 4 to 8))
Change From Baseline in Vital Sign: Pulse Rate(Baseline (Day 1) and TOC visit (Day 4 to 8))
Number of Participants With Urinalysis Dipstick Results(Baseline (Day 1) and TOC visit (Day 4 to 8))
Absolute Values in Potential of Hydrogen (pH) of Urine(Baseline (Day 1) and TOC visit (Day 4 to 8))
Change From Baseline in Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(Baseline (Day 1) and TOC visit (Day 4 to 8))
Change From Baseline in Vital Sign: Temperature(Baseline (Day 1) and TOC visit (Day 4 to 8))
Absolute Values in Specific Gravity of Urine(Baseline (Day 1) and TOC visit (Day 4 to 8))