Trial Outcomes & Findings for Zoliflodacin in Uncomplicated Gonorrhoea (NCT NCT03959527)

NCT ID: NCT03959527

Last Updated: 2025-10-08

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1011 participants
• Primary outcome timeframe: Day 6 (+/- 2)
• Results posted on: 2025-10-08

Participant Flow

A total 1011 participants were screened, of which 81 were screen failure

Participant milestones

Measure	Zoliflodacin Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	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
Overall Study STARTED	621	309
Overall Study COMPLETED	571	285
Overall Study NOT COMPLETED	50	24

Reasons for withdrawal

Measure	Zoliflodacin Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	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
Overall Study Withdrawal by Subject	8	3
Overall Study Lost to Follow-up	31	15
Overall Study Did not meet eligibility criteria	1	1
Overall Study Protocol Violation	10	5

Baseline Characteristics

Zoliflodacin in Uncomplicated Gonorrhoea

Baseline characteristics by cohort

Measure	Zoliflodacin n=621 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=309 Participants 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	Total n=930 Participants Total of all reporting groups
Age, Continuous	30.0 years STANDARD_DEVIATION 9.56 • n=5 Participants	29.2 years STANDARD_DEVIATION 9.13 • n=7 Participants	29.7 years STANDARD_DEVIATION 9.42 • n=5 Participants
Sex: Female, Male Female	77 Participants n=5 Participants	38 Participants n=7 Participants	115 Participants n=5 Participants
Sex: Female, Male Male	544 Participants n=5 Participants	271 Participants n=7 Participants	815 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	18 Participants n=5 Participants	13 Participants n=7 Participants	31 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	603 Participants n=5 Participants	296 Participants n=7 Participants	899 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	8 Participants n=5 Participants	1 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) Asian	193 Participants n=5 Participants	92 Participants n=7 Participants	285 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Black or African American	349 Participants n=5 Participants	165 Participants n=7 Participants	514 Participants n=5 Participants
Race (NIH/OMB) White	66 Participants n=5 Participants	47 Participants n=7 Participants	113 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Netherlands	49 participants n=5 Participants	20 participants n=7 Participants	69 participants n=5 Participants
Region of Enrollment Belgium	6 participants n=5 Participants	3 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment United States	107 participants n=5 Participants	51 participants n=7 Participants	158 participants n=5 Participants
Region of Enrollment South Africa	278 participants n=5 Participants	146 participants n=7 Participants	424 participants n=5 Participants
Region of Enrollment Thailand	181 participants n=5 Participants	89 participants n=7 Participants	270 participants n=5 Participants

PRIMARY outcome

Timeframe: 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

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

Outcome measures

Measure	Zoliflodacin n=506 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=238 Participants 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
Microbiological Cure Rate for Zoliflodacin Compared to a Combination of a Single Dose of Ceftriaxone and Azithromycin.	90.9 percentage of participants Interval 88.1 to 93.3	96.2 percentage of participants Interval 92.9 to 98.3

SECONDARY outcome

Timeframe: Day 30

Population: The safety population included all randomized participants who received any part of trial treatment

Incidence, severity, causality and seriousness of treatment-emergent adverse events (including clinically significant abnormal laboratory values/procedures i.e., physical examination per protocol)

Outcome measures

Measure	Zoliflodacin n=619 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=308 Participants 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
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	144 Participants
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	76 Participants
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	0 Participants
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	0 Participants
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	0 Participants
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	82 Participants
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	44 Participants
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	18 Participants
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	0 Participants
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	0 Participants

SECONDARY outcome

Timeframe: 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

Proportion of participants with microbiological cure as determined by NG culture at pharyngeal sites at test of cure visit in micro-ITT (Pharyngeal).

Outcome measures

Measure	Zoliflodacin n=53 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=28 Participants 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
Microbiological Cure Rate of Pharyngeal Gonorrhoea of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin.	42 Participants	22 Participants

SECONDARY outcome

Timeframe: 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

Proportion of participants with microbiological cure as determined by NG culture at rectal sites at test of cure visit in micro-ITT (Rectal).

Outcome measures

Measure	Zoliflodacin n=79 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=35 Participants 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
Microbiological Cure Rate of Rectal Gonorrhoea of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin.	69 Participants	31 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Zoliflodacin n=460 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=220 Participants 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
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	194 Participants

SECONDARY outcome

Timeframe: 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

Proportion of female participants with microbiological cure, as determined by NG culture at cervical site of infection, at TOC in micro-ITT (Urogenital) population

Outcome measures

Measure	Zoliflodacin n=50 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=18 Participants 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
Microbiological Cure Rate Among Females, After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin	48 Participants	16 Participants

SECONDARY outcome

Timeframe: 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

Proportion of male participants with microbiological cure as determined by NG culture at urethral site of infection at TOC visit, in micro-ITT population

Outcome measures

Measure	Zoliflodacin n=456 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=220 Participants 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
Microbiological Cure Rate Among Males, After Administration of a Single Dose of Zoliflodacin Compared to a Single Dose of Ceftriaxone and Azithromycin	412 Participants	213 Participants

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Zoliflodacin n=492 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=233 Participants 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
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	190 Participants

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Zoliflodacin n=45 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=24 Participants 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
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	12 Participants

SECONDARY outcome

Timeframe: 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

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.

Outcome measures

Measure	Zoliflodacin n=73 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=30 Participants 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
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	27 Participants

SECONDARY outcome

Timeframe: 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

Arithmetic mean plasma concentration (ng/mL) of zoliflodacin following oral administration of single oral dose of zoliflodacin 3 g

Outcome measures

Measure	Zoliflodacin n=22 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	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
Arithmetic Mean Plasma Concentration of Zoliflodacin	580 ng/mL Standard Deviation 830	—

SECONDARY outcome

Timeframe: 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).

Arithmetic mean plasma concentration (ng/mL) of zoliflodacin following a single oral dose administration of zoliflodacin 3 g

Outcome measures

Measure	Zoliflodacin n=23 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	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
Arithmetic Mean Plasma Concentration of Zoliflodacin	14500 ng/mL Standard Deviation 9610	—

SECONDARY outcome

Timeframe: 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.

Arithmetic mean plasma concentration (ng/mL) of zoliflodacin following administration of a single oral dose of zoliflodacin 3 g

Outcome measures

Measure	Zoliflodacin n=23 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	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
Arithmetic Mean Plasma Concentration of Zoliflodacin	32300 ng/mL Standard Deviation 8630	—

SECONDARY outcome

Timeframe: 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.

Arithmetic mean plasma concentration (ng/mL) of zoliflodacin following administration of a single oral dose zoliflodacin 3 g

Outcome measures

Measure	Zoliflodacin n=23 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	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
Arithmetic Mean Plasma Concentration of Zoliflodacin	19300 ng/mL Standard Deviation 6000	—

SECONDARY outcome

Timeframe: 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.

Arithmetic mean plasma concentration (ng/mL) of zoliflodacin following administration of a single oral dose of zoliflodacin 3 g

Outcome measures

Measure	Zoliflodacin n=23 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	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
Arithmetic Mean Plasma Concentration of Zoliflodacin	3270 ng/mL Standard Deviation 1560	—

SECONDARY outcome

Timeframe: 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.

Geometric mean time to last (Tlast) plasma concentration above the lower limit of quantitation

Outcome measures

Measure	Zoliflodacin n=23 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	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
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 outcome

Timeframe: 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.

Geometric mean time to maximum plasma concentration (Tmax) after a single, oral, 3 g dose of zoliflodacin

Outcome measures

Measure	Zoliflodacin n=23 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	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
Evaluation of the Plasma PK Profile(Tmax) After a Single, Oral, 3 g Dose of Zoliflodacin	4.83 hours Geometric Coefficient of Variation 41.0	—

SECONDARY outcome

Timeframe: 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.

Geometric mean maximum plasma concentration (Cmax) after a single, oral 3 g dose of zoliflodacin

Outcome measures

Measure	Zoliflodacin n=23 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	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
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 outcome

Timeframe: 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.

Geometric mean plasma area under the concentration-time curve (AUC0-last) from time zero to the last concentration above lower level of quantification

Outcome measures

Measure	Zoliflodacin n=23 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	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
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 outcome

Timeframe: Day 1

Population: Number of participants in urogenital micro-ITT without missing data for the specified visit

Antimicrobial susceptibility to azithromycin (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline (Day 1)

Outcome measures

Measure	Zoliflodacin n=506 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=238 Participants 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
Antimicrobial Susceptibility (Azithromycin) Profile of NG Isolates Obtained at Baseline (Day 1)	1 mg/L Interval 0.06 to 8.0	1 mg/L Interval 0.06 to 8.0

SECONDARY outcome

Timeframe: Day 6

Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit

Antimicrobial susceptibility to azithromycin (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC

Outcome measures

Measure	Zoliflodacin n=15 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	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
Antimicrobial Susceptibility (Azithromycin) Profile of NG Isolates Obtained at Test of Cure Visit.	0.25 mg/L Interval 0.06 to 2.0	—

SECONDARY outcome

Timeframe: Day 1

Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit

Antimicrobial susceptibility to cefixime (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline

Outcome measures

Measure	Zoliflodacin n=506 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=238 Participants 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
Antimicrobial Susceptibility (Cefixime) Profile of NG Isolates Obtained at Baseline	0.06 mg/L Interval 0.002 to 0.5	0.06 mg/L Interval 0.002 to 0.5

SECONDARY outcome

Timeframe: Day 6

Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit

Antimicrobial susceptibility to cefixime (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC

Outcome measures

Measure	Zoliflodacin n=15 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	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
Antimicrobial Susceptibility (Cefixime) Profile of NG Isolates Obtained at Test of Cure Visit.	0.015 mg/L Interval 0.002 to 0.03	—

SECONDARY outcome

Timeframe: Day 1

Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit

Antimicrobial susceptibility to ceftriaxone (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline

Outcome measures

Measure	Zoliflodacin n=506 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=238 Participants 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
Antimicrobial Susceptibility (Ceftriaxone) Profile of NG Isolates Obtained at Baseline	0.015 mg/L Interval 0.002 to 0.25	0.015 mg/L Interval 0.002 to 0.12

SECONDARY outcome

Timeframe: Day 6

Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit

Antimicrobial susceptibility to ceftriaxone (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC

Outcome measures

Measure	Zoliflodacin n=15 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	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
Antimicrobial Susceptibility (Ceftriaxone) Profile of NG Isolates Obtained at Test of Cure Visit.	0.015 mg/L Interval 0.002 to 0.015	—

SECONDARY outcome

Timeframe: Day 1

Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit

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)

Outcome measures

Measure	Zoliflodacin n=506 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=238 Participants 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
Antimicrobial Susceptibility (Ciprofloxacin) Profile of NG Isolates Obtained at Baseline	2 mg/L Interval 0.0005 to 2.0	2 mg/L Interval 0.002 to 2.0

SECONDARY outcome

Timeframe: Day 6

Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit

Antimicrobial susceptibility to azithromycin (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC

Outcome measures

Measure	Zoliflodacin n=15 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	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
Antimicrobial Susceptibility (Ciprofloxacin) Profile of NG Isolates Obtained at Test of Cure Visit	2 mg/L Interval 0.004 to 2.0	—

SECONDARY outcome

Timeframe: Day 1

Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit

Antimicrobial susceptibility to gentamicin (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline

Outcome measures

Measure	Zoliflodacin n=506 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=238 Participants 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
Antimicrobial Susceptibility (Gentamicin) Profile of NG Isolates Obtained at Baseline	8 mg/L Interval 1.0 to 16.0	8 mg/L Interval 0.5 to 16.0

SECONDARY outcome

Timeframe: Day 6

Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit

Antimicrobial susceptibility to gentamicin (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC

Outcome measures

Measure	Zoliflodacin n=15 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	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
Antimicrobial Susceptibility (Gentamicin) Profile of NG Isolates Obtained at Test of Cure Visit.	8 mg/L Interval 4.0 to 8.0	—

SECONDARY outcome

Timeframe: Day 1

Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit

Antimicrobial susceptibility to spectinomycin (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline

Outcome measures

Measure	Zoliflodacin n=506 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=238 Participants 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
Antimicrobial Susceptibility (Spectinomycin) Profile of NG Isolates Obtained at Baseline	32 mg/L Interval 8.0 to 64.0	32 mg/L Interval 8.0 to 64.0

SECONDARY outcome

Timeframe: Day 6

Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit

Antimicrobial susceptibility to spectinomycin (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC

Outcome measures

Measure	Zoliflodacin n=15 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	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
Antimicrobial Susceptibility (Spectinomycin) Profile of NG Isolates Obtained at Test of Cure Visit	32 mg/L Interval 16.0 to 32.0	—

SECONDARY outcome

Timeframe: Day 1

Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit

Antimicrobial susceptibility to tetracycline (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline

Outcome measures

Measure	Zoliflodacin n=506 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=238 Participants 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
Antimicrobial Susceptibility (Tetracycline) Profile of NG Isolates Obtained at Baseline	4 mg/L Interval 0.12 to 4.0	4 mg/L Interval 0.12 to 4.0

SECONDARY outcome

Timeframe: Day 6

Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit

Antimicrobial susceptibility to tetracycline (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC

Outcome measures

Measure	Zoliflodacin n=15 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	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
Antimicrobial Susceptibility (Tetracycline) Profile of NG Isolates Obtained at Test of Cure Visit	4 mg/L Interval 0.5 to 4.0	—

SECONDARY outcome

Timeframe: Day 1

Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit

Antimicrobial susceptibility to zolflodacin (MIC90) - profile of gonococcal strains isolated from urogenital site at baseline

Outcome measures

Measure	Zoliflodacin n=506 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=238 Participants 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
Antimicrobial Susceptibility (Zoliflodacin) Profile of NG Isolates Obtained at Baseline	0.12 mg/L Interval 0.008 to 0.5	0.12 mg/L Interval 0.008 to 0.25

SECONDARY outcome

Timeframe: Day 6

Population: Number of participants in urogenital Micro-ITT without missing data for the specified visit

Antimicrobial susceptibility to zoliflodacin (MIC90) - profile of gonococcal strains isolated from urogenital site at TOC

Outcome measures

Measure	Zoliflodacin n=15 Participants Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	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
Antimicrobial Susceptibility (Zoliflodacin) Profile of NG Isolates Obtained at Test of Cure Visit	0.12 mg/L Interval 0.008 to 0.25	—

Adverse Events

Zoliflodacin

Serious events: 0 serious events

Other events: 162 other events

Deaths: 0 deaths

Ceftriaxone and Azithromycin Combination

Serious events: 0 serious events

Other events: 107 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Zoliflodacin n=619 participants at risk Participant in this arm will receive a single dose of zoliflodacin. zoliflodacin: Dose: 3g, oral administration	Ceftriaxone and Azithromycin Combination n=308 participants at risk 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
Blood and lymphatic system disorders Neutropenia	6.8% 42/619 • Number of events 42 • 30 days (+/- 3 days) All adverse events (AE) that occurred between Day -1 to Day 30 are reported, irrespective of causality assessment. Any AE that occurs after the reporting period assessed as possibly related to the investigational treatment should also be reported. For screening failure participants, AEs are reported up until the date the participant was determined to be a screening failure. Beyond that date, only serious or medically relevant protocol-related events will be followed-up.	7.8% 24/308 • Number of events 24 • 30 days (+/- 3 days) All adverse events (AE) that occurred between Day -1 to Day 30 are reported, irrespective of causality assessment. Any AE that occurs after the reporting period assessed as possibly related to the investigational treatment should also be reported. For screening failure participants, AEs are reported up until the date the participant was determined to be a screening failure. Beyond that date, only serious or medically relevant protocol-related events will be followed-up.
Blood and lymphatic system disorders Leukopenia	3.9% 24/619 • Number of events 24 • 30 days (+/- 3 days) All adverse events (AE) that occurred between Day -1 to Day 30 are reported, irrespective of causality assessment. Any AE that occurs after the reporting period assessed as possibly related to the investigational treatment should also be reported. For screening failure participants, AEs are reported up until the date the participant was determined to be a screening failure. Beyond that date, only serious or medically relevant protocol-related events will be followed-up.	2.3% 7/308 • Number of events 7 • 30 days (+/- 3 days) All adverse events (AE) that occurred between Day -1 to Day 30 are reported, irrespective of causality assessment. Any AE that occurs after the reporting period assessed as possibly related to the investigational treatment should also be reported. For screening failure participants, AEs are reported up until the date the participant was determined to be a screening failure. Beyond that date, only serious or medically relevant protocol-related events will be followed-up.
Gastrointestinal disorders Diarrhoea	2.4% 15/619 • Number of events 15 • 30 days (+/- 3 days) All adverse events (AE) that occurred between Day -1 to Day 30 are reported, irrespective of causality assessment. Any AE that occurs after the reporting period assessed as possibly related to the investigational treatment should also be reported. For screening failure participants, AEs are reported up until the date the participant was determined to be a screening failure. Beyond that date, only serious or medically relevant protocol-related events will be followed-up.	7.1% 22/308 • Number of events 22 • 30 days (+/- 3 days) All adverse events (AE) that occurred between Day -1 to Day 30 are reported, irrespective of causality assessment. Any AE that occurs after the reporting period assessed as possibly related to the investigational treatment should also be reported. For screening failure participants, AEs are reported up until the date the participant was determined to be a screening failure. Beyond that date, only serious or medically relevant protocol-related events will be followed-up.
Gastrointestinal disorders Nausea	2.6% 16/619 • Number of events 16 • 30 days (+/- 3 days) All adverse events (AE) that occurred between Day -1 to Day 30 are reported, irrespective of causality assessment. Any AE that occurs after the reporting period assessed as possibly related to the investigational treatment should also be reported. For screening failure participants, AEs are reported up until the date the participant was determined to be a screening failure. Beyond that date, only serious or medically relevant protocol-related events will be followed-up.	3.9% 12/308 • Number of events 13 • 30 days (+/- 3 days) All adverse events (AE) that occurred between Day -1 to Day 30 are reported, irrespective of causality assessment. Any AE that occurs after the reporting period assessed as possibly related to the investigational treatment should also be reported. For screening failure participants, AEs are reported up until the date the participant was determined to be a screening failure. Beyond that date, only serious or medically relevant protocol-related events will be followed-up.
General disorders Injection site pain	0.81% 5/619 • Number of events 6 • 30 days (+/- 3 days) All adverse events (AE) that occurred between Day -1 to Day 30 are reported, irrespective of causality assessment. Any AE that occurs after the reporting period assessed as possibly related to the investigational treatment should also be reported. For screening failure participants, AEs are reported up until the date the participant was determined to be a screening failure. Beyond that date, only serious or medically relevant protocol-related events will be followed-up.	12.3% 38/308 • Number of events 38 • 30 days (+/- 3 days) All adverse events (AE) that occurred between Day -1 to Day 30 are reported, irrespective of causality assessment. Any AE that occurs after the reporting period assessed as possibly related to the investigational treatment should also be reported. For screening failure participants, AEs are reported up until the date the participant was determined to be a screening failure. Beyond that date, only serious or medically relevant protocol-related events will be followed-up.
Investigations Neutrophil count decreased	3.4% 21/619 • Number of events 21 • 30 days (+/- 3 days) All adverse events (AE) that occurred between Day -1 to Day 30 are reported, irrespective of causality assessment. Any AE that occurs after the reporting period assessed as possibly related to the investigational treatment should also be reported. For screening failure participants, AEs are reported up until the date the participant was determined to be a screening failure. Beyond that date, only serious or medically relevant protocol-related events will be followed-up.	4.9% 15/308 • Number of events 15 • 30 days (+/- 3 days) All adverse events (AE) that occurred between Day -1 to Day 30 are reported, irrespective of causality assessment. Any AE that occurs after the reporting period assessed as possibly related to the investigational treatment should also be reported. For screening failure participants, AEs are reported up until the date the participant was determined to be a screening failure. Beyond that date, only serious or medically relevant protocol-related events will be followed-up.
Nervous system disorders Headache	9.9% 61/619 • Number of events 65 • 30 days (+/- 3 days) All adverse events (AE) that occurred between Day -1 to Day 30 are reported, irrespective of causality assessment. Any AE that occurs after the reporting period assessed as possibly related to the investigational treatment should also be reported. For screening failure participants, AEs are reported up until the date the participant was determined to be a screening failure. Beyond that date, only serious or medically relevant protocol-related events will be followed-up.	4.5% 14/308 • Number of events 15 • 30 days (+/- 3 days) All adverse events (AE) that occurred between Day -1 to Day 30 are reported, irrespective of causality assessment. Any AE that occurs after the reporting period assessed as possibly related to the investigational treatment should also be reported. For screening failure participants, AEs are reported up until the date the participant was determined to be a screening failure. Beyond that date, only serious or medically relevant protocol-related events will be followed-up.
Nervous system disorders Dizziness	3.4% 21/619 • Number of events 21 • 30 days (+/- 3 days) All adverse events (AE) that occurred between Day -1 to Day 30 are reported, irrespective of causality assessment. Any AE that occurs after the reporting period assessed as possibly related to the investigational treatment should also be reported. For screening failure participants, AEs are reported up until the date the participant was determined to be a screening failure. Beyond that date, only serious or medically relevant protocol-related events will be followed-up.	1.6% 5/308 • Number of events 5 • 30 days (+/- 3 days) All adverse events (AE) that occurred between Day -1 to Day 30 are reported, irrespective of causality assessment. Any AE that occurs after the reporting period assessed as possibly related to the investigational treatment should also be reported. For screening failure participants, AEs are reported up until the date the participant was determined to be a screening failure. Beyond that date, only serious or medically relevant protocol-related events will be followed-up.

Additional Information

Dr Alison Luckey

GARDP

Phone: +41 22 559 05 39

Email: aluckey@gardp.org

Results disclosure agreements

• Principal investigator is a sponsor employee The sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor can require changes to the communication and can extend the embargo for a further 90 days in order to enable the sponsor to take steps to protect its proprietary information and/or Intellectual Property Rights.
• Publication restrictions are in place

Restriction type: OTHER