Clinical trial NCT03959527: Zoliflodacin in Uncomplicated Gonorrhoea
Official title: A Multi-center, Randomized, Open-label, Non Inferiority Trial to Evaluate the Efficacy and Safety of a Single, Oral Dose of Zoliflodacin Compared to a Combination of a Single Intramuscular Dose of Ceftriaxone and a Single Oral Dose of Azithromycin in the Treatment of Patients With Uncomplicated Gonorrhoea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gonorrhea
Lead sponsor: Global Antibiotics Research and Development Partnership
Sponsor class: OTHER
First posted: 2019-05-22
Enrollment: 1011
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single dose of Zoliflodacin or comparators combination in single dose: ceftriaxone and azithromycin
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Age ≥ 12 years old (if enrolment of minors is in agreement with local regulations and Ethics guidance)
2. Weight ≥ 35 kg
3. 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)
4. For females of child-bearing potential, a negative urine pregnancy test at screening
5. 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.
6. For males with a female partner of child-bearing age, willingness to delay conception for 28 days after treatment
7. Willingness to comply with trial protocol
8. Willingness to undergo HIV testing
9. Willingness to abstain from sexual intercourse or use condoms for vaginal, anal and oral sex until end of trial visit
10. 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).

    Exclusion Criteria:
11. Confirmed or suspected complicated or disseminated gonorrhoea
12. Pregnant or breastfeeding women
13. Known concomitant infection which would require immediate additional systemic antibiotics with activity against NG (e.g. CT infection)
14. Use of any systemic or intravaginal antibiotics with activity against NG within 30 days prior to screening
15. Use of systemic corticoid drugs or other immunosuppressive therapy within 30 days prior to screening
16. 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
17. Cytotoxic or radiation therapy within 30 days prior to screening
18. 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
19. History of urogenital sex-reassignment surgery
20. Immunosuppression as evidenced by medical history, clinical examination or a recent (≤ 1 month) CD4 count \<200 cells/μL
21. Know clinically relevant cardiac pro-arrhythmic conditions such as cardiac arrhythmia, congenital or documented QT prolongation
22. Known history of severe allergy to cephalosporin, penicillin, monobactams, carbapenems or macrolide antibiotics
23. 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)
24. 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
25. History of alcohol or drug abuse within 12 months prior to screening which would compromise trial participation in the judgment of the investigator
26. 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
27. Individuals whom, in the judgement of the investigator, are unlikely or unable to comply with this trial protocol
28. Previous randomisation in this clinical trial.
29. Use of moderate or strong CYP3A4 inhibitors within 30 days or five half-lives of the drug, whichever is greater, prior to screening

Primary outcomes:
measure: Microbiological Cure Rate for Zoliflodacin Compared to a Combination of a Single Dose of Ceftriaxone and Azithromycin.
timeFrame: Day 6 (+/- 2)
Secondary outcomes:
measure: Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin.
timeFrame: Day 30
measure: Microbiological Cure Rate of Pharyngeal Gonorrhoea Will be Determined After Administration of a Single Dose of Zoliflodacin Compared to a Combination of a Single Dose of Ceftriaxone and Azithromycin.
timeFrame: Day 6
measure: Microbiological Cure Rate of Rectal Gonorrhoea Will be Determined After Administration of a Single Dose of Zoliflodacin Compared to a Combination of a Single Dose of Ceftriaxone and Azithromycin.
timeFrame: Day 6
measure: The Clinical Cure Rate of Symptomatic Gonorrhoea in Male Participants Will be Determined After Administration of a Single Dose of Zoliflodacin Compared to a Combination of Single Dose of Ceftriaxone and Azithromycin.
timeFrame: Day 6
measure: Microbiological Cure Rate of Urogenital Gonorrhoea Among Women, After Administration of a Single, Oral, 3 g Dose of Zoliflodacin Compared to a Combination of a Single IM 500 mg Dose of Ceftriaxone and a Single 1 g Oral Dose of Azithromycin
timeFrame: Day 6
measure: Microbiological Cure Rate of Urogenital Gonorrhoea Among Men, After Administration of a Single, Oral, 3 g Dose of Zoliflodacin Compared to a Combination of a Single IM 500 mg Dose of Ceftriaxone and a Single 1 g Oral Dose of Azithromycin
timeFrame: Day 6
measure: Antimicrobial Susceptibility Profile Will be Determined of Gonococcal Strains Isolated From Participants With Uncomplicated Gonorrhoea at Baseline and the Test of Cure Visit.
timeFrame: Day 6
measure: The Proportion of Participants With Eradication of NG NAAT at TOC Will be Determined From Urogenital Specimens After Administration of a Single Dose of Zoliflodacin Compared to a Combination of a Single Dose of Ceftriaxone and Azithromycin.
timeFrame: Day 6
measure: Proportion of Participants With Eradication of NG NAAT at TOC Determined From Pharyngeal Specimens After Administration of a Single Dose of Zoliflodacin Compared to a Combination of a Single Dose of Ceftriaxone and Azithromycin.
timeFrame: Day 6
measure: Proportion of Participants With Eradication of NG NAAT at TOC Determined From Rectal Specimens After Administration of a Single Dose of Zoliflodacin Compared to a Combination of a Single Dose of Ceftriaxone and Azithromycin.
timeFrame: Day 6
measure: Arithmetic Mean Plasma Concentration of Zoliflodacin
timeFrame: 15 min - 1 hour
measure: Arithmetic Mean Plasma Concentration of Zoliflodacin
timeFrame: 2-2.5 h
measure: Arithmetic Mean Plasma Concentration of Zoliflodacin
timeFrame: 4.5 - 5h
measure: Arithmetic Mean Plasma Concentration of Zoliflodacin
timeFrame: 10 -12 h
measure: Arithmetic Mean Plasma Concentration of Zoliflodacin
timeFrame: 24 - 36 h
measure: Evaluation of the Plasma PK Profile After a Single, Oral, 3 g Dose of Zoliflodacin
timeFrame: Day 2
measure: Evaluation of the Plasma PK Profile After a Single, Oral, 3 g Dose of Zoliflodacin
timeFrame: Day 2
measure: Evaluation of the Plasma PK Profile After a Single, Oral, 3 g Dose of Zoliflodacin
timeFrame: Day 2
measure: Evaluation of the Plasma PK Profile After a Single, Oral, 3 g Dose of Zoliflodacin
timeFrame: Day 2
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Jefferson County Department of Health
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: San Francisco
country: United States
facility: San Francisco Department Of Public Health City Clinic
state: California
city: Indianapolis
country: United States
facility: Bell Flower Clinic
state: Indiana
city: New Orleans
country: United States
facility: Louisiana State University Health Sciences Center
state: Louisiana
city: Seattle
country: United States
facility: Public Health - Seattle & King County STD Clinic
state: Washington
city: Antwerp
country: Belgium
facility: Institute of Tropical Medicine
city: Amsterdam
country: Netherlands
facility: Public Health Service (GGD) Amsterdam / STI Outpatient Clinic
city: Bothas Hill
country: South Africa
facility: SAMRC Botha's Hill Clinical Research Site
city: Cape Town
country: South Africa
facility: Masiphumelele Research Site
city: Elandsdoorn
country: South Africa
facility: Ndlovu Research Centre
city: Johannesburg
country: South Africa
facility: Wits RHI
city: Soshanguve
country: South Africa
facility: Setshaba Research Centre
city: Tongaat
country: South Africa
facility: SAMRC Tongaat Clinical Research Site
city: Bangkok
country: Thailand
facility: Bangrak STI Center
city: Bangkok
country: Thailand
facility: Institute of HIV Research and Innovation
city: Bangkok
country: Thailand
facility: Silom Community Clinic
Study officials:
References: