Gonorrhea
Conditions
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.
Interventions
DRUGzoliflodacin
Dose: 3g, oral administration
DRUGceftriaxone
Dose: 500mg, Intra-Muscular (IM) administration
DRUGazithromycin
Dose: 1g, oral administration
Sponsors
Global Antibiotics Research and Development Partnership
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single dose of Zoliflodacin or comparators combination in single dose: ceftriaxone and azithromycin
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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 |
| 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 | 15 min - 1 hour | Arithmetic mean plasma concentration (ng/mL) of zoliflodacin following oral administration of 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 |
| 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) |
| 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 (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 |
| 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 |
Countries
Belgium, Netherlands, South Africa, Thailand, United States
Participant flow
Pre-assignment details
A total 1011 participants were screened, of which 81 were screen failure
Participants by arm
| Arm | Count |
|---|---|
| Zoliflodacin Participant in this arm will receive a single dose of zoliflodacin.
zoliflodacin: Dose: 3g, oral administration | 621 |
| Ceftriaxone and Azithromycin Combination Participant in this arm will receive a single dose of comparators combination (ceftriaxone and azithromycin).
ceftriaxone: Dose: 500mg, Intra-Muscular (IM) administration
azithromycin: Dose: 1g, oral administration | 309 |
| Total | 930 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not meet eligibility criteria | 1 | 1 |
| Overall Study | Lost to Follow-up | 31 | 15 |
| Overall Study | Protocol Violation | 10 | 5 |
| Overall Study | Withdrawal by Subject | 8 | 3 |
Baseline characteristics
| Characteristic | Zoliflodacin | Ceftriaxone and Azithromycin Combination | Total |
|---|---|---|---|
| Age, Continuous | 30.0 years STANDARD_DEVIATION 9.56 | 29.2 years STANDARD_DEVIATION 9.13 | 29.7 years STANDARD_DEVIATION 9.42 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 13 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 603 Participants | 296 Participants | 899 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 8 Participants | 1 Participants | 9 Participants |
| Race (NIH/OMB) Asian | 193 Participants | 92 Participants | 285 Participants |
| Race (NIH/OMB) Black or African American | 349 Participants | 165 Participants | 514 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 66 Participants | 47 Participants | 113 Participants |
| Region of Enrollment Belgium | 6 participants | 3 participants | 9 participants |
| Region of Enrollment Netherlands | 49 participants | 20 participants | 69 participants |
| Region of Enrollment South Africa | 278 participants | 146 participants | 424 participants |
| Region of Enrollment Thailand | 181 participants | 89 participants | 270 participants |
| Region of Enrollment United States | 107 participants | 51 participants | 158 participants |
| Sex: Female, Male Female | 77 Participants | 38 Participants | 115 Participants |
| Sex: Female, Male Male | 544 Participants | 271 Participants | 815 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 619 | 0 / 308 |
| other Total, other adverse events | 162 / 619 | 107 / 308 |
| serious Total, serious adverse events | 0 / 619 | 0 / 308 |
Outcome results
Primary
Microbiological Cure Rate for Zoliflodacin Compared to a Combination of a Single Dose of Ceftriaxone and Azithromycin.
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
Time frame: Day 6 (+/- 2)
Population: micro-ITT (urogenital): all randomized participants who had a positive NG culture from the relevant anatomical site at baseline and whose baseline AST result showed no pre-existing resistance to both ceftriaxone and azithromycin
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Zoliflodacin | Microbiological Cure Rate for Zoliflodacin Compared to a Combination of a Single Dose of Ceftriaxone and Azithromycin. | 90.9 percentage of participants |
| Ceftriaxone and Azithromycin Combination | Microbiological Cure Rate for Zoliflodacin Compared to a Combination of a Single Dose of Ceftriaxone and Azithromycin. | 96.2 percentage of participants |
Comparison: Point estimate for the treatment difference in proportion of ceftriaxone/azithromycin combination and zoliflodacin with microbiological cure and 2-sided 95% CI calculated by Newcombe score method.95% CI: [1.38, 8.65]
Secondary
Antimicrobial Susceptibility (Azithromycin) Profile of NG Isolates Obtained at Baseline (Day 1)
Antimicrobial susceptibility to azithromycin (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline (Day 1)
Time frame: Day 1
Population: Number of participants in urogenital micro-ITT without missing data for the specified visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Zoliflodacin | Antimicrobial Susceptibility (Azithromycin) Profile of NG Isolates Obtained at Baseline (Day 1) | 1 mg/L |
| Ceftriaxone and Azithromycin Combination | Antimicrobial Susceptibility (Azithromycin) Profile of NG Isolates Obtained at Baseline (Day 1) | 1 mg/L |
Secondary
Antimicrobial Susceptibility (Azithromycin) Profile of NG Isolates Obtained at Test of Cure Visit.
Antimicrobial susceptibility to azithromycin (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC
Time frame: Day 6
Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Zoliflodacin | Antimicrobial Susceptibility (Azithromycin) Profile of NG Isolates Obtained at Test of Cure Visit. | 0.25 mg/L |
Secondary
Antimicrobial Susceptibility (Cefixime) Profile of NG Isolates Obtained at Baseline
Antimicrobial susceptibility to cefixime (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline
Time frame: Day 1
Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Zoliflodacin | Antimicrobial Susceptibility (Cefixime) Profile of NG Isolates Obtained at Baseline | 0.06 mg/L |
| Ceftriaxone and Azithromycin Combination | Antimicrobial Susceptibility (Cefixime) Profile of NG Isolates Obtained at Baseline | 0.06 mg/L |
Secondary
Antimicrobial Susceptibility (Cefixime) Profile of NG Isolates Obtained at Test of Cure Visit.
Antimicrobial susceptibility to cefixime (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC
Time frame: Day 6
Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Zoliflodacin | Antimicrobial Susceptibility (Cefixime) Profile of NG Isolates Obtained at Test of Cure Visit. | 0.015 mg/L |
Secondary
Antimicrobial Susceptibility (Ceftriaxone) Profile of NG Isolates Obtained at Baseline
Antimicrobial susceptibility to ceftriaxone (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline
Time frame: Day 1
Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Zoliflodacin | Antimicrobial Susceptibility (Ceftriaxone) Profile of NG Isolates Obtained at Baseline | 0.015 mg/L |
| Ceftriaxone and Azithromycin Combination | Antimicrobial Susceptibility (Ceftriaxone) Profile of NG Isolates Obtained at Baseline | 0.015 mg/L |
Secondary
Antimicrobial Susceptibility (Ceftriaxone) Profile of NG Isolates Obtained at Test of Cure Visit.
Antimicrobial susceptibility to ceftriaxone (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC
Time frame: Day 6
Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Zoliflodacin | Antimicrobial Susceptibility (Ceftriaxone) Profile of NG Isolates Obtained at Test of Cure Visit. | 0.015 mg/L |
Secondary
Antimicrobial Susceptibility (Ciprofloxacin) Profile of NG Isolates Obtained at Baseline
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)
Time frame: Day 1
Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Zoliflodacin | Antimicrobial Susceptibility (Ciprofloxacin) Profile of NG Isolates Obtained at Baseline | 2 mg/L |
| Ceftriaxone and Azithromycin Combination | Antimicrobial Susceptibility (Ciprofloxacin) Profile of NG Isolates Obtained at Baseline | 2 mg/L |
Secondary
Antimicrobial Susceptibility (Ciprofloxacin) Profile of NG Isolates Obtained at Test of Cure Visit
Antimicrobial susceptibility to azithromycin (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC
Time frame: Day 6
Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Zoliflodacin | Antimicrobial Susceptibility (Ciprofloxacin) Profile of NG Isolates Obtained at Test of Cure Visit | 2 mg/L |
Secondary
Antimicrobial Susceptibility (Gentamicin) Profile of NG Isolates Obtained at Baseline
Antimicrobial susceptibility to gentamicin (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline
Time frame: Day 1
Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Zoliflodacin | Antimicrobial Susceptibility (Gentamicin) Profile of NG Isolates Obtained at Baseline | 8 mg/L |
| Ceftriaxone and Azithromycin Combination | Antimicrobial Susceptibility (Gentamicin) Profile of NG Isolates Obtained at Baseline | 8 mg/L |
Secondary
Antimicrobial Susceptibility (Gentamicin) Profile of NG Isolates Obtained at Test of Cure Visit.
Antimicrobial susceptibility to gentamicin (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC
Time frame: Day 6
Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Zoliflodacin | Antimicrobial Susceptibility (Gentamicin) Profile of NG Isolates Obtained at Test of Cure Visit. | 8 mg/L |
Secondary
Antimicrobial Susceptibility (Spectinomycin) Profile of NG Isolates Obtained at Baseline
Antimicrobial susceptibility to spectinomycin (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline
Time frame: Day 1
Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Zoliflodacin | Antimicrobial Susceptibility (Spectinomycin) Profile of NG Isolates Obtained at Baseline | 32 mg/L |
| Ceftriaxone and Azithromycin Combination | Antimicrobial Susceptibility (Spectinomycin) Profile of NG Isolates Obtained at Baseline | 32 mg/L |
Secondary
Antimicrobial Susceptibility (Spectinomycin) Profile of NG Isolates Obtained at Test of Cure Visit
Antimicrobial susceptibility to spectinomycin (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC
Time frame: Day 6
Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Zoliflodacin | Antimicrobial Susceptibility (Spectinomycin) Profile of NG Isolates Obtained at Test of Cure Visit | 32 mg/L |
Secondary
Antimicrobial Susceptibility (Tetracycline) Profile of NG Isolates Obtained at Baseline
Antimicrobial susceptibility to tetracycline (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline
Time frame: Day 1
Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Zoliflodacin | Antimicrobial Susceptibility (Tetracycline) Profile of NG Isolates Obtained at Baseline | 4 mg/L |
| Ceftriaxone and Azithromycin Combination | Antimicrobial Susceptibility (Tetracycline) Profile of NG Isolates Obtained at Baseline | 4 mg/L |
Secondary
Antimicrobial Susceptibility (Tetracycline) Profile of NG Isolates Obtained at Test of Cure Visit
Antimicrobial susceptibility to tetracycline (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC
Time frame: Day 6
Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Zoliflodacin | Antimicrobial Susceptibility (Tetracycline) Profile of NG Isolates Obtained at Test of Cure Visit | 4 mg/L |
Secondary
Antimicrobial Susceptibility (Zoliflodacin) Profile of NG Isolates Obtained at Baseline
Antimicrobial susceptibility to zolflodacin (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline
Time frame: Day 1
Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Zoliflodacin | Antimicrobial Susceptibility (Zoliflodacin) Profile of NG Isolates Obtained at Baseline | 0.12 mg/L |
| Ceftriaxone and Azithromycin Combination | Antimicrobial Susceptibility (Zoliflodacin) Profile of NG Isolates Obtained at Baseline | 0.12 mg/L |
Secondary
Antimicrobial Susceptibility (Zoliflodacin) Profile of NG Isolates Obtained at Test of Cure Visit
Antimicrobial susceptibility to zoliflodacin (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC
Time frame: Day 6
Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Zoliflodacin | Antimicrobial Susceptibility (Zoliflodacin) Profile of NG Isolates Obtained at Test of Cure Visit | 0.12 mg/L |
Secondary
Arithmetic Mean Plasma Concentration of Zoliflodacin
Arithmetic mean plasma concentration (ng/mL) of zoliflodacin following oral administration of single oral dose of zoliflodacin 3 g
Time frame: 15 min - 1 hour
Population: Of the 23 participants included in the PK Population Set (all participants randomized to the zoliflodacin group who consent to participate to the PK sub-trial and from whom at least one valid PK sample post treatment is obtained), quantifiable zoliflodacin concentrations were available for only 22 participants at this time point
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zoliflodacin | Arithmetic Mean Plasma Concentration of Zoliflodacin | 580 ng/mL | Standard Deviation 830 |
Secondary
Arithmetic Mean Plasma Concentration of Zoliflodacin
Arithmetic mean plasma concentration (ng/mL) of zoliflodacin following administration of a single oral dose of zoliflodacin 3 g
Time frame: 24 - 36 h
Population: The PK population will include all participants randomized to the zoliflodacin group who consent to participate to the PK sub-trial and from whom at least one valid PK sample post treatment is obtained.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zoliflodacin | Arithmetic Mean Plasma Concentration of Zoliflodacin | 3270 ng/mL | Standard Deviation 1560 |
Secondary
Arithmetic Mean Plasma Concentration of Zoliflodacin
Arithmetic mean plasma concentration (ng/mL) of zoliflodacin following administration of a single oral dose zoliflodacin 3 g
Time frame: 10 -12 h
Population: The PK population will include all participants randomized to the zoliflodacin group who consent to participate to the PK sub-trial and from whom at least one valid PK sample post treatment is obtained.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zoliflodacin | Arithmetic Mean Plasma Concentration of Zoliflodacin | 19300 ng/mL | Standard Deviation 6000 |
Secondary
Arithmetic Mean Plasma Concentration of Zoliflodacin
Arithmetic mean plasma concentration (ng/mL) of zoliflodacin following administration of a single oral dose of zoliflodacin 3 g
Time frame: 4.5 - 5h
Population: The PK population will include all participants randomized to the zoliflodacin group who consent to participate to the PK sub-trial and from whom at least one valid PK sample post treatment is obtained.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zoliflodacin | Arithmetic Mean Plasma Concentration of Zoliflodacin | 32300 ng/mL | Standard Deviation 8630 |
Secondary
Arithmetic Mean Plasma Concentration of Zoliflodacin
Arithmetic mean plasma concentration (ng/mL) of zoliflodacin following a single oral dose administration of zoliflodacin 3 g
Time frame: 2-2.5 h
Population: PK Population Set (all participants randomized to the zoliflodacin group who consent to participate to the PK sub-trial and from whom at least one valid PK sample post treatment is obtained).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zoliflodacin | Arithmetic Mean Plasma Concentration of Zoliflodacin | 14500 ng/mL | Standard Deviation 9610 |
Secondary
Eradication of Pharyngeal NG NAAT at TOC After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin.
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.
Time frame: Day 6
Population: Of those participants included in the micro-ITT (Pharyngeal) analysis set (N=81) (i.e., all randomized participants who had a positive NG culture from the pharyngeal site at baseline and whose baseline AST result showed no pre-existing resistance to both ceftriaxone and azithromycin), a total of 69 had positive pharyngeal NG NAAT result
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zoliflodacin | Eradication of Pharyngeal NG NAAT at TOC After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin. | 28 Participants |
| Ceftriaxone and Azithromycin Combination | Eradication of Pharyngeal NG NAAT at TOC After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin. | 12 Participants |
Secondary
Eradication of Rectal NG NAAT at TOC After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin.
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.
Time frame: Day 6
Population: Of those participants included in the micro-ITT (Rectal) analysis set (N=114) (i.e., all randomized participants who had a positive NG culture from the rectal site at baseline and whose baseline AST result showed no pre-existing resistance to both ceftriaxone and azithromycin), a total of 103 had a positive NG NAAT result at baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zoliflodacin | Eradication of Rectal NG NAAT at TOC After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin. | 60 Participants |
| Ceftriaxone and Azithromycin Combination | Eradication of Rectal NG NAAT at TOC After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin. | 27 Participants |
Secondary
Eradication of Urogenital NG NAAT at TOC After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin.
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.
Time frame: Day 6
Population: Of those participants included in the micro-ITT (Urogenital) analysis set (i.e., all randomized participants who had a positive NG culture from the urogenital site at baseline and whose baseline AST result showed no pre-existing resistance to both ceftriaxone and azithromycin) (N=744), a total of 725 had a positive NG NAAT result at baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zoliflodacin | Eradication of Urogenital NG NAAT at TOC After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin. | 405 Participants |
| Ceftriaxone and Azithromycin Combination | Eradication of Urogenital NG NAAT at TOC After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin. | 190 Participants |
Secondary
Evaluation of the Plasma PK Profile After a Single, Oral, 3 g Dose of Zoliflodacin
Geometric mean plasma area under the concentration-time curve (AUC0-last) from time zero to the last concentration above lower level of quantification
Time frame: Day 2
Population: PK population: all participants randomized to the zoliflodacin group who consent to participate to the PK sub-trial and from whom at least one valid PK sample post treatment is obtained.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zoliflodacin | Evaluation of the Plasma PK Profile After a Single, Oral, 3 g Dose of Zoliflodacin | 330000 h*ng/mL | Geometric Coefficient of Variation 26.5 |
Secondary
Evaluation of the Plasma PK Profile (Cmax) After a Single, Oral, 3 g Dose of Zoliflodacin
Geometric mean maximum plasma concentration (Cmax) after a single, oral 3 g dose of zoliflodacin
Time frame: Day 2
Population: PK population: all participants randomized to the zoliflodacin group who consent to participate to the PK sub-trial and from whom at least one valid PK sample post treatment is obtained.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zoliflodacin | Evaluation of the Plasma PK Profile (Cmax) After a Single, Oral, 3 g Dose of Zoliflodacin | 31800 ng/mL | Geometric Coefficient of Variation 27.3 |
Secondary
Evaluation of the Plasma PK Profile (Tlast) After a Single, Oral, 3 g Dose of Zoliflodacin
Geometric mean time to last (Tlast) plasma concentration above the lower limit of quantitation
Time frame: Day 2
Population: PK population: all participants randomized to the zoliflodacin group who consent to participate to the PK sub-trial and from whom at least one valid PK sample post treatment is obtained.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zoliflodacin | Evaluation of the Plasma PK Profile (Tlast) After a Single, Oral, 3 g Dose of Zoliflodacin | 24.6 hours | Geometric Coefficient of Variation 3.2 |
Secondary
Evaluation of the Plasma PK Profile(Tmax) After a Single, Oral, 3 g Dose of Zoliflodacin
Geometric mean time to maximum plasma concentration (Tmax) after a single, oral, 3 g dose of zoliflodacin
Time frame: Day 2
Population: PK population: all participants randomized to the zoliflodacin group who consent to participate to the PK sub-trial and from whom at least one valid PK sample post treatment is obtained.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Zoliflodacin | Evaluation of the Plasma PK Profile(Tmax) After a Single, Oral, 3 g Dose of Zoliflodacin | 4.83 hours | Geometric Coefficient of Variation 41 |
Secondary
Microbiological Cure Rate Among Females, After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin
Proportion of female participants with microbiological cure, as determined by NG culture at cervical site of infection, at TOC in micro-ITT (Urogenital) population
Time frame: Day 6
Population: micro-ITT (Urogenital): all randomized participants who had a positive NG culture from the urogenital site at baseline and whose baseline AST result showed no pre-existing resistance to both ceftriaxone and azithromycin
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zoliflodacin | Microbiological Cure Rate Among Females, After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin | 48 Participants |
| Ceftriaxone and Azithromycin Combination | Microbiological Cure Rate Among Females, After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin | 16 Participants |
Secondary
Microbiological Cure Rate Among Males, After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin
Proportion of male participants with microbiological cure as determined by NG culture at urethral site of infection at TOC visit, in micro-ITT population
Time frame: Day 6
Population: micro-ITT (urogenital): all randomized participants who had a positive NG culture from the urogenital site at baseline and whose baseline AST result showed no pre-existing resistance to both ceftriaxone and azithromycin
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zoliflodacin | Microbiological Cure Rate Among Males, After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin | 412 Participants |
| Ceftriaxone and Azithromycin Combination | Microbiological Cure Rate Among Males, After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin | 213 Participants |
Secondary
Microbiological Cure Rate of Pharyngeal Gonorrhoea of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin.
Proportion of participants with microbiological cure as determined by NG culture at pharyngeal sites at test of cure visit in micro-ITT (Pharyngeal).
Time frame: Day 6
Population: Micro-ITT (Pharyngeal) population: all randomized participants who had a positive NG culture from the pharyngeal site at baseline and whose baseline AST result showed no pre-existing resistance to both ceftriaxone and azithromycin
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zoliflodacin | Microbiological Cure Rate of Pharyngeal Gonorrhoea of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin. | 42 Participants |
| Ceftriaxone and Azithromycin Combination | Microbiological Cure Rate of Pharyngeal Gonorrhoea of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin. | 22 Participants |
Secondary
Microbiological Cure Rate of Rectal Gonorrhoea of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin.
Proportion of participants with microbiological cure as determined by NG culture at rectal sites at test of cure visit in micro-ITT (Rectal).
Time frame: Day 6
Population: Micro-ITT (Rectal): all randomized participants who had a positive NG culture from the rectal site at baseline and whose baseline AST result showed no pre-existing resistance to both ceftriaxone and azithromycin
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zoliflodacin | Microbiological Cure Rate of Rectal Gonorrhoea of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin. | 69 Participants |
| Ceftriaxone and Azithromycin Combination | Microbiological Cure Rate of Rectal Gonorrhoea of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin. | 31 Participants |
Secondary
Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin.
Incidence, severity, causality and seriousness of treatment-emergent adverse events (including clinically significant abnormal laboratory values/procedures i.e., physical examination per protocol)
Time frame: Day 30
Population: The safety population included all randomized participants who received any part of trial treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zoliflodacin | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | All AEs | 287 Participants |
| Zoliflodacin | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | Maximum severity CTCAE Grade 1 or Mild | 157 Participants |
| Zoliflodacin | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | Serious AEs | 0 Participants |
| Zoliflodacin | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | Maximum severity CTCAE Grade 2 or Moderate | 109 Participants |
| Zoliflodacin | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | Related AEs | 117 Participants |
| Zoliflodacin | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | Maximum severity CTCAE Grade 3 or Severe | 20 Participants |
| Zoliflodacin | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | AEs leading to treatment discontinuation | 0 Participants |
| Zoliflodacin | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | Maximum severity CTCAE Grade 4 or Life-Threatening | 1 Participants |
| Zoliflodacin | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | AEs leading to death | 0 Participants |
| Zoliflodacin | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | Maximum severity CTCAE Grade 5 or Death | 0 Participants |
| Ceftriaxone and Azithromycin Combination | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | AEs leading to death | 0 Participants |
| Ceftriaxone and Azithromycin Combination | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | Maximum severity CTCAE Grade 5 or Death | 0 Participants |
| Ceftriaxone and Azithromycin Combination | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | All AEs | 144 Participants |
| Ceftriaxone and Azithromycin Combination | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | Related AEs | 76 Participants |
| Ceftriaxone and Azithromycin Combination | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | Serious AEs | 0 Participants |
| Ceftriaxone and Azithromycin Combination | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | AEs leading to treatment discontinuation | 0 Participants |
| Ceftriaxone and Azithromycin Combination | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | Maximum severity CTCAE Grade 1 or Mild | 82 Participants |
| Ceftriaxone and Azithromycin Combination | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | Maximum severity CTCAE Grade 2 or Moderate | 44 Participants |
| Ceftriaxone and Azithromycin Combination | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | Maximum severity CTCAE Grade 3 or Severe | 18 Participants |
| Ceftriaxone and Azithromycin Combination | Safety of a Single Dose of Zoliflodacin Will be Assessed Compared to a Combination a Single Dose of Ceftriaxone and Azithromycin. | Maximum severity CTCAE Grade 4 or Life-Threatening | 0 Participants |
Secondary
The Clinical Cure Rate in Male Participants After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin.
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.
Time frame: Day 6
Population: Clinical Cure population: all participants assigned male at birth included in the Micro-ITT (urogenital) population and who had at least one sign or symptom of urethral gonorrhea at baseline.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Zoliflodacin | The Clinical Cure Rate in Male Participants After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin. | 375 Participants |
| Ceftriaxone and Azithromycin Combination | The Clinical Cure Rate in Male Participants After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin. | 194 Participants |