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

NCT04010539 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 1165772018-001780-23
• Study Type: interventional
• Target: 628
• Locations: 6 countries
• Sites: 51

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.

Conditions

Gonorrhea

Keywords

Urogenital Gonorrhea; Gepotidacin; Neisseria gonorrhoeae; Efficacy; Phase 3

Outcome Measures

Primary Outcomes (1)

• 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)

  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.

  Baseline (Day 1) and TOC visit (Day 4 to 8)

Secondary Outcomes (19)

• 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)

• Number of Participants With Any Treatment-emergent Adverse Events (TEAEs) and Any Serious Adverse Events (SAEs)

  Up to 21 days

• 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)

Study Arms (2)

Participants receiving Gepotidacin

EXPERIMENTAL

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

Participants receiving Ceftriaxone plus Azithromycin

ACTIVE COMPARATOR

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; Drug: Azithromycin

Interventions

Gepotidacin DRUG

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.

Participants receiving Gepotidacin

Ceftriaxone DRUG

Ceftriaxone is available as sterile powder for reconstitution. It will be administered as one 500-mg IM dose at the study site.

Participants receiving Ceftriaxone plus Azithromycin

Azithromycin DRUG

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.

Participants receiving Ceftriaxone plus Azithromycin

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (51)

GSK Investigational Site

Los Angeles, California, 90036, United States

Location

GSK Investigational Site

Palm Springs, California, 92262, United States

Location

GSK Investigational Site

DeLand, Florida, 32720, United States

Location

GSK Investigational Site

Orlando, Florida, 32803, United States

Location

GSK Investigational Site

Decatur, Georgia, 30033, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46202, United States

Location

GSK Investigational Site

New Orleans, Louisiana, 70119, United States

Location

GSK Investigational Site

Springfield, Massachusetts, 01105, United States

Location

GSK Investigational Site

Fayetteville, North Carolina, 28303-5537, United States

Location

GSK Investigational Site

Greensboro, North Carolina, 27405, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44109, United States

Location

GSK Investigational Site

Houston, Texas, 77098, United States

Location

GSK Investigational Site

Longview, Texas, 75602, United States

Location

GSK Investigational Site

Darlinghurst, New South Wales, 2010, Australia

Location

GSK Investigational Site

Darlinghurst, Sydney, New South Wales, 2010, Australia

Location

GSK Investigational Site

Southport, Queensland, 4215, Australia

Location

GSK Investigational Site

Carlton, Victoria, 3053, Australia

Location

GSK Investigational Site

Prahran, Victoria, 3181, Australia

Location

GSK Investigational Site

Munich, Bavaria, 81675, Germany

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60590, Germany

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60596, Germany

Location

GSK Investigational Site

Cologne, North Rhine-Westphalia, 50924, Germany

Location

GSK Investigational Site

Berlin, 10243, Germany

Location

GSK Investigational Site

Berlin, 10439, Germany

Location

GSK Investigational Site

Hamburg, 20146, Germany

Location

GSK Investigational Site

München, 80336, Germany

Location

GSK Investigational Site

Guadalajara, Jalisco, 44160, Mexico

Location

GSK Investigational Site

Guadalajara, Jalisco, 44280, Mexico

Location

GSK Investigational Site

Monterrey, 64460, Mexico

Location

GSK Investigational Site

Barcelona, 08036, Spain

Location

GSK Investigational Site

Barcelona, 08041, Spain

Location

GSK Investigational Site

Barcelona, 08950, Spain

Location

GSK Investigational Site

Barcelona, ?08015, Spain

Location

GSK Investigational Site

Barcelona, ?08907, Spain

Location

GSK Investigational Site

Bilbao, 48010, Spain

Location

GSK Investigational Site

Madrid, 28010, Spain

Location

GSK Investigational Site

Madrid, 28034, Spain

Location

GSK Investigational Site

Madrid, 28040, Spain

Location

GSK Investigational Site

Madrid, 28046, Spain

Location

GSK Investigational Site

Seville, 41013, Spain

Location

GSK Investigational Site

Birmingham, B4 6DH, United Kingdom

Location

GSK Investigational Site

Brighton, BN2 1ES, United Kingdom

Location

GSK Investigational Site

Edinburgh, EH3 9ES, United Kingdom

Location

GSK Investigational Site

Leeds, LS1 3EX, United Kingdom

Location

GSK Investigational Site

London, E9 6SR, United Kingdom

Location

GSK Investigational Site

London, W2 1NY, United Kingdom

Location

GSK Investigational Site

London, W6 7AL, United Kingdom

Location

GSK Investigational Site

London, WC1E 6JB, United Kingdom

Location

GSK Investigational Site

Manchester, M13 0FH, United Kingdom

Location

GSK Investigational Site

Reading, RG1 5SL, United Kingdom

Location

GSK Investigational Site

St Helens, WA9 3DA, United Kingdom

Location

Related Publications (3)

• Ross JDC, Wilson J, Workowski KA, Taylor SN, Lewis DA, Gatsi S, Flight W, Scangarella-Oman NE, Jakielaszek C, Lythgoe D, Powell M, Janmohamed S, Absalon J, Perry C. Oral gepotidacin for the treatment of uncomplicated urogenital gonorrhoea (EAGLE-1): a phase 3 randomised, open-label, non-inferiority, multicentre study. Lancet. 2025 May 3;405(10489):1608-1620. doi: 10.1016/S0140-6736(25)00628-2. Epub 2025 Apr 14.

  PMID: 40245902 DERIVED

• Perry CR, Scangarella-Oman NE, Millns H, Flight W, Gatsi S, Jakielaszek C, Janmohamed S, Lewis DA. Efficacy and Safety of Gepotidacin as Treatment of Uncomplicated Urogenital Gonorrhea (EAGLE-1): Design of a Randomized, Comparator-Controlled, Phase 3 Study. Infect Dis Ther. 2023 Sep;12(9):2307-2320. doi: 10.1007/s40121-023-00862-6. Epub 2023 Sep 26.

  PMID: 37751016 DERIVED

• 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.

  PMID: 36255258 DERIVED

MeSH Terms

Conditions

Gonorrhea

Interventions

gepotidacin; Ceftriaxone; Azithromycin

Condition Hierarchy (Ancestors)

Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sexually Transmitted Diseases, Bacterial; Sexually Transmitted Diseases; Communicable Diseases; Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2019
• First Posted: July 8, 2019
• Study Start: October 21, 2019
• Primary Completion: October 10, 2023
• Study Completion: October 10, 2023
• Last Updated: May 30, 2024
• Results First Posted: May 30, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

GB (11); ES (11); DE (8); ME (3); US (13); AU (5)