Zoliflodacin in Uncomplicated Gonorrhoea
- Conditions
- Gonorrhea
- Interventions
- Registration Number
- NCT03959527
- Lead Sponsor
- Global Antibiotics Research and Development Partnership
- Brief Summary
This trial is a multi-center, open label, randomized controlled, non-inferiority phase III trial evaluating the safety and efficacy of a 3 g oral dose of zoliflodacin compared to a combination of a single intra-muscular 500 mg dose of ceftriaxone and a single 1 g oral dose of azithromycin for the treatment of uncomplicated gonorrhoea.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1011
- Age ≥ 12 years old (if enrolment of minors is in agreement with local regulations and Ethics guidance)
- Weight ≥ 35 kg
- Signs and symptoms consistent with urethral or cervical gonorrhoea OR Urethral or cervical uncomplicated gonorrhoea as determined by either a positive culture or NAAT or Gram stain or methylene blue test/gentian violet stain in the past 14 days prior to screening OR Unprotected sexual contact with an individual reported to be infected with NG in the past 14 days prior to screening (confirmation by a positive NAAT, Gram stain or methylene blue test/ gentian violet stain or culture)
- For females of child-bearing potential, a negative urine pregnancy test at screening
- For females of child bearing potential, use of highly effective contraception for at least 28 days prior to screening and during at least 28 days after treatment. Females on oral contraceptives must also use a barrier contraception method during participation in the study.
- For males with a female partner of child-bearing age, willingness to delay conception for 28 days after treatment
- Willingness to comply with trial protocol
- Willingness to undergo HIV testing
- Willingness to abstain from sexual intercourse or use condoms for vaginal, anal and oral sex until end of trial visit
- Willingness and ability to give written informed consent or be consented by a legal representative or provide assent and parental consent (for minors, as appropriate).
- Confirmed or suspected complicated or disseminated gonorrhoea
- Pregnant or breastfeeding women
- Known concomitant infection which would require immediate additional systemic antibiotics with activity against NG (e.g. CT infection)
- Use of any systemic or intravaginal antibiotics with activity against NG within 30 days prior to screening
- Use of systemic corticoid drugs or other immunosuppressive therapy within 30 days prior to screening
- Use of moderate or strong CYP3A4 inducers (e.g. efavirenz, rifampicin, carbamazepine, phenobarbital) within 30 days or five half-lives of the drug, whichever is greater, prior to screening
- Cytotoxic or radiation therapy within 30 days prior to screening
- Known chronic renal, hepatic, hematologic impairment or other condition interfering with the absorption, distribution or elimination of the drug based on medical history and physical examination
- History of urogenital sex-reassignment surgery
- Immunosuppression as evidenced by medical history, clinical examination or a recent (≤ 1 month) CD4 count <200 cells/μL
- Know clinically relevant cardiac pro-arrhythmic conditions such as cardiac arrhythmia, congenital or documented QT prolongation
- Known history of severe allergy to cephalosporin, penicillin, monobactams, carbapenems or macrolide antibiotics
- Known or suspected allergies or hypersensitivities to lidocaine, methylparaben, lactose or any of the components of the study drugs (refer to the zoliflodacin IB and SmPC for the comparators treatments)
- Receipt or planned receipt of an investigational product in a clinical trial within 30 days or five half-lives of the drug, whichever is greater, prior to screening until end of participation to this clinical trial
- History of alcohol or drug abuse within 12 months prior to screening which would compromise trial participation in the judgment of the investigator
- Severe medical or psychiatric condition which, in the opinion of the investigator, may increase the risk associated with trial participation or may interfere with the interpretation of trial results or affect the individual's ability to provide informed consent
- Individuals whom, in the judgement of the investigator, are unlikely or unable to comply with this trial protocol
- Previous randomisation in this clinical trial.
- Use of moderate or strong CYP3A4 inhibitors within 30 days or five half-lives of the drug, whichever is greater, prior to screening
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description zoliflodacin zoliflodacin Participant in this arm will receive a single dose of zoliflodacin. ceftriaxone and azithromycin combination ceftriaxone Participant in this arm will receive a single dose of comparators combination (ceftriaxone and azithromycin). ceftriaxone and azithromycin combination azithromycin Participant in this arm will receive a single dose of comparators combination (ceftriaxone and azithromycin).
- Primary Outcome Measures
Name Time Method Microbiological Cure Rate for Zoliflodacin Compared to a Combination of a Single Dose of Ceftriaxone and Azithromycin. Day 6 (+/- 2) Proportion of participants with microbiological cure as determined by culture at urethral or cervical sites at test of cure visit in micro-ITT (urogenital) analysis set
- Secondary Outcome Measures
Name Time Method Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. Day 30 Incidence, severity, causality and seriousness of treatment-emergent adverse events (including clinically significant abnormal laboratory values/procedures i.e., physical examination per protocol)
Microbiological Cure Rate of Pharyngeal Gonorrhoea of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin. Day 6 Proportion of participants with microbiological cure as determined by NG culture at pharyngeal sites at test of cure visit in micro-ITT (Pharyngeal).
Microbiological Cure Rate of Rectal Gonorrhoea of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin. Day 6 Proportion of participants with microbiological cure as determined by NG culture at rectal sites at test of cure visit in micro-ITT (Rectal).
The Clinical Cure Rate in Male Participants After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin. Day 6 Proportion of male at birth participants experiencing resolution of signs and symptoms of urogenital gonococcal infection that were present at enrolment, at test of cure visit in Clinical Cure Population.
Microbiological Cure Rate Among Females, After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin Day 6 Proportion of female participants with microbiological cure, as determined by NG culture at cervical site of infection, at TOC in micro-ITT (Urogenital) population
Microbiological Cure Rate Among Males, After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin Day 6 Proportion of male participants with microbiological cure as determined by NG culture at urethral site of infection at TOC visit, in micro-ITT population
Eradication of Urogenital NG NAAT at TOC After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin. Day 6 Proportion of participants with a positive NG NAAT result from urethral or cervical sites at baseline and a negative NG NAAT result at test of cure visit in micro-ITT analysis set.
Eradication of Pharyngeal NG NAAT at TOC After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin. Day 6 Proportion of participants with a positive NG NAAT at baseline from pharyngeal sites and a negative NG NAAT at test of cure visit in micro-ITT analysis set.
Eradication of Rectal NG NAAT at TOC After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin. Day 6 Proportion of participants with a positive NG NAAT from rectal sites at baseline and a negative NG NAAT at test of cure visit in micro-ITT analysis set.
Arithmetic Mean Plasma Concentration of Zoliflodacin 24 - 36 h Arithmetic mean plasma concentration (ng/mL) of zoliflodacin following administration of a single oral dose of zoliflodacin 3 g
Evaluation of the Plasma PK Profile (Tlast) After a Single, Oral, 3 g Dose of Zoliflodacin Day 2 Geometric mean time to last (Tlast) plasma concentration above the lower limit of quantitation
Evaluation of the Plasma PK Profile(Tmax) After a Single, Oral, 3 g Dose of Zoliflodacin Day 2 Geometric mean time to maximum plasma concentration (Tmax) after a single, oral, 3 g dose of zoliflodacin
Evaluation of the Plasma PK Profile (Cmax) After a Single, Oral, 3 g Dose of Zoliflodacin Day 2 Geometric mean maximum plasma concentration (Cmax) after a single, oral 3 g dose of zoliflodacin
Evaluation of the Plasma PK Profile After a Single, Oral, 3 g Dose of Zoliflodacin Day 2 Geometric mean plasma area under the concentration-time curve (AUC0-last) from time zero to the last concentration above lower level of quantification
Antimicrobial Susceptibility (Azithromycin) Profile of NG Isolates Obtained at Baseline (Day 1) Day 1 Antimicrobial susceptibility to azithromycin (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline (Day 1)
Antimicrobial Susceptibility (Azithromycin) Profile of NG Isolates Obtained at Test of Cure Visit. Day 6 Antimicrobial susceptibility to azithromycin (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC
Antimicrobial Susceptibility (Cefixime) Profile of NG Isolates Obtained at Baseline Day 1 Antimicrobial susceptibility to cefixime (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline
Antimicrobial Susceptibility (Cefixime) Profile of NG Isolates Obtained at Test of Cure Visit. Day 6 Antimicrobial susceptibility to cefixime (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC
Antimicrobial Susceptibility (Ceftriaxone) Profile of NG Isolates Obtained at Baseline Day 1 Antimicrobial susceptibility to ceftriaxone (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline
Antimicrobial Susceptibility (Ceftriaxone) Profile of NG Isolates Obtained at Test of Cure Visit. Day 6 Antimicrobial susceptibility to ceftriaxone (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC
Antimicrobial Susceptibility (Ciprofloxacin) Profile of NG Isolates Obtained at Baseline Day 1 Antimicrobial susceptibility to ciprofloxacin (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline (zoliflodacin arm only since no microbiological failures in comparator arm)
Antimicrobial Susceptibility (Ciprofloxacin) Profile of NG Isolates Obtained at Test of Cure Visit Day 6 Antimicrobial susceptibility to azithromycin (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC
Antimicrobial Susceptibility (Gentamicin) Profile of NG Isolates Obtained at Baseline Day 1 Antimicrobial susceptibility to gentamicin (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline
Antimicrobial Susceptibility (Gentamicin) Profile of NG Isolates Obtained at Test of Cure Visit. Day 6 Antimicrobial susceptibility to gentamicin (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC
Antimicrobial Susceptibility (Spectinomycin) Profile of NG Isolates Obtained at Baseline Day 1 Antimicrobial susceptibility to spectinomycin (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline
Antimicrobial Susceptibility (Spectinomycin) Profile of NG Isolates Obtained at Test of Cure Visit Day 6 Antimicrobial susceptibility to spectinomycin (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC
Antimicrobial Susceptibility (Tetracycline) Profile of NG Isolates Obtained at Baseline Day 1 Antimicrobial susceptibility to tetracycline (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline
Antimicrobial Susceptibility (Tetracycline) Profile of NG Isolates Obtained at Test of Cure Visit Day 6 Antimicrobial susceptibility to tetracycline (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC
Antimicrobial Susceptibility (Zoliflodacin) Profile of NG Isolates Obtained at Baseline Day 1 Antimicrobial susceptibility to zolflodacin (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline
Antimicrobial Susceptibility (Zoliflodacin) Profile of NG Isolates Obtained at Test of Cure Visit Day 6 Antimicrobial susceptibility to zoliflodacin (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC
Trial Locations
- Locations (17)
Jefferson County Department of Health
🇺🇸Birmingham, Alabama, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
San Francisco Department Of Public Health City Clinic
🇺🇸San Francisco, California, United States
Bell Flower Clinic
🇺🇸Indianapolis, Indiana, United States
Louisiana State University Health Sciences Center
🇺🇸New Orleans, Louisiana, United States
Public Health - Seattle & King County STD Clinic
🇺🇸Seattle, Washington, United States
Institute of Tropical Medicine
🇧🇪Antwerp, Belgium
Public Health Service (GGD) Amsterdam / STI Outpatient Clinic
🇳🇱Amsterdam, Netherlands
SAMRC Botha's Hill Clinical Research Site
🇿🇦Bothas Hill, South Africa
Masiphumelele Research Site
🇿🇦Cape Town, South Africa
Scroll for more (7 remaining)Jefferson County Department of Health🇺🇸Birmingham, Alabama, United States