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

NCT ID: NCT04010539

Last Updated: 2024-05-30

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

628 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-21

Study Completion Date

2023-10-10

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.

Detailed Description

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Conditions

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Gonorrhea

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Gepotidacin

Intervention Type 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 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.

Group Type ACTIVE_COMPARATOR

Ceftriaxone

Intervention Type DRUG

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

Azithromycin

Intervention Type 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.

Interventions

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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.

Intervention Type DRUG

Ceftriaxone

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

Intervention Type 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.

Intervention Type DRUG

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.
Minimum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

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GSK Investigational Site

Los Angeles, California, United States

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Palm Springs, California, United States

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DeLand, Florida, United States

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Orlando, Florida, United States

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Decatur, Georgia, United States

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Indianapolis, Indiana, United States

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New Orleans, Louisiana, United States

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Springfield, Massachusetts, United States

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Fayetteville, North Carolina, United States

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Greensboro, North Carolina, United States

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Cleveland, Ohio, United States

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Houston, Texas, United States

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Longview, Texas, United States

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Darlinghurst, New South Wales, Australia

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Darlinghurst, Sydney, New South Wales, Australia

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Southport, Queensland, Australia

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Carlton, Victoria, Australia

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Prahran, Victoria, Australia

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Munich, Bavaria, Germany

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Frankfurt am Main, Hesse, Germany

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Frankfurt am Main, Hesse, Germany

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Cologne, North Rhine-Westphalia, Germany

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Berlin, , Germany

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Berlin, , Germany

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Hamburg, , Germany

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München, , Germany

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Guadalajara, Jalisco, Mexico

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Guadalajara, Jalisco, Mexico

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Monterrey, , Mexico

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Barcelona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Bilbao, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Seville, , Spain

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Birmingham, , United Kingdom

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Brighton, , United Kingdom

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Edinburgh, , United Kingdom

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Leeds, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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London, , United Kingdom

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Manchester, , United Kingdom

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Reading, , United Kingdom

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St Helens, , United Kingdom

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Countries

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United States Australia Germany Mexico Spain United Kingdom

References

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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.

Reference Type DERIVED
PMID: 40245902 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37751016 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36255258 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2018-001780-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

116577

Identifier Type: -

Identifier Source: org_study_id

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