Last updated: 04/18/2025 11:50:37
A study evaluating efficacy and safety of gepotidacin compared with ceftriaxone plus azithromycin in the treatment of uncomplicated urogenital gonorrhea
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:
Number of participants with culture-confirmed bacterial eradication of Neisseria gonorrhoeae from the urogenital site at the Test-of-Cure (TOC)
Timeframe: From Day 4 to Day 8
Secondary outcomes:
Number of participants with culture-confirmed bacterial eradication of Neisseria gonorrhoeae from the rectal site at the TOC
Timeframe: From Day 4 to Day 8
Number of participants with culture-confirmed bacterial eradication of Neisseria gonorrhoeae from the pharyngeal site at the TOC
Timeframe: From Day 4 to Day 8
Number of participants with treatment-emergent adverse events and serious adverse events (SAEs)
Timeframe: 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)
Timeframe: Baseline (Day 1) and from Day 4 to Day 8
Change from Baseline in hemoglobin level (Grams per Liter)
Timeframe: Baseline (Day 1) and from Day 4 to Day 8
Change from Baseline in hematocrit level (Proportion of red blood cells in blood)
Timeframe: Baseline (Day 1) and from Day 4 to Day 8
Change from Baseline in red blood cell (RBC) count (Trillion cells per liter)
Timeframe: Baseline (Day 1) and from Day 4 to Day 8
Change from Baseline in mean corpuscular hemoglobin (MCH) (Picograms)
Timeframe: Baseline (Day 1) and from Day 4 to Day 8
Change from Baseline in mean corpuscular volume (MCV) (Femtoliters)
Timeframe: 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)
Timeframe: Baseline (Day 1) and from Day 4 to Day 8
Change from Baseline in total bilirubin, direct bilirubin and creatinine levels (Micromoles per liter)
Timeframe: Baseline (Day 1) and from Day 4 to Day 8
Change from Baseline in albumin and total protein levels (Grams per liter)
Timeframe: 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)
Timeframe: Baseline (Day 1) and from Day 4 to Day 8
Number of participants with abnormal urinalysis Dipstick results
Timeframe: From Day 4 to Day 8
Change from Baseline in specific gravity of urine (Ratio)
Timeframe: 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)
Timeframe: Baseline (Day 1) and from Day 4 to Day 8
Change from Baseline in pulse rate (Beats per minute)
Timeframe: Baseline (Day 1) and from Day 4 to Day 8
Change from Baseline in body temperature (Degrees Celsius)
Timeframe: Baseline (Day 1) and from Day 4 to Day 8
Interventions:
Drug: Gepotidacin
Drug: Ceftriaxone
Drug: Azithromycin
Enrollment:
628
Observational study model:
Not applicable
Primary completion date:
2023-10-10
Time perspective:
Not applicable
Clinical publications:
Jonathan D C Ross, Janet Wilson, Kimberly A Workowski, Stephanie N Taylor, David A Lewis, Sally Gatsi, William Flight, Nicole E Scangarella-Oman, Charles Jakielaszek, Dan Lythgoe, Marcy Powell, Salim Janmohamed, Judith Absalon, Caroline Perry. Oral gepotidacin for the treatment of uncomplicated urogenital gonorrhoea (EAGLE-1): a phase 3 randomised, open-label, non-inferiority, multicentre study. The Lancet. 2025-4; doi:10.1016/S0140-6736(25)00628-2 https://doi.org/10.1016/s0140-6736(25)00628-2
PMID: 40245902
DOI: 10.1016/S0140-6736(25)00628-2
Medical condition
Gonorrhea
Product
Not applicable
Collaborators
NA
Study date(s)
October 2019 to October 2023
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
12+ years
Accepts healthy volunteers
No
- Participants must be >=12 years of age at the time of signing the informed consent.
- Participants having body weight of >45 kilogram (kg).
- 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.
Inclusion and exclusion 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.
Trial location(s)
Location
GSK Investigational Site
Fayetteville, NC, United States, 28303-5537
Status
Study Complete
Location
GSK Investigational Site
Indianapolis, IN, United States, 46202
Status
Study Complete
Location
GSK Investigational Site
New Orleans Louisiana, LA, United States, 70119
Status
Study Complete
Location
GSK Investigational Site
Palm Springs, CA, United States, 92262
Status
Study Complete
Location
GSK Investigational Site
Reading Berkshire, United Kingdom, RG1 5SL
Status
Study Complete
Study documents
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2023-10-10
Actual study completion date
2023-10-10
Plain language summaries
Summary of results in plain language
Available language(s): English, Catalan, German, Spanish (Mexico), Spanish, Spanish (United States)
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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