Trial Outcomes & Findings for To Assess Bioavailability, Food Effect and Pharmacokinetics of Gepotidacin Tablets: A Phase I, Single-Dose, 2 Part Study in Healthy Subjects. (NCT NCT02853435)

Results Overview

Blood samples for pharmacokinetic (PK) analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1a. For each sample, 3 milliliters (mL) of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. The PK Parameter Population consisted of all participants in the PK Population, for whom valid and evaluable PK parameters were derived. Statistics has been presented on geometric least square (LS) means.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

48 participants

Primary outcome timeframe

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period

Results posted on

2020-10-08

Participant Flow

This study was conducted across 2 centers in the United States from 04-August-2016 to 18-October-2017. Since the relative bio-availability of the roller compacted(RC) tablet formulation under fasted and fed conditions had been previously evaluated in Study BTZ117349 (NCT02045849), Part 1b was not conducted.

A total of 48 participants were enrolled in the study of which 26 participants were randomized in Part 1a, 10 participants were randomized in Part 2 and 12 participants were part of Placebo-controlled Part 3.

Participant milestones

Participant milestones
Measure	Gepotidacin-R Then Gepotidacin RC Then Gepotidacin HSWG Participants received gepotidacin 1500 milligrams (mg) (3 x 500 mg) (Reference \[R\]) capsules in treatment period 1 followed by gepotidacin 1500 mg (2 x 750 mg) related RC tablets in treatment period 2 followed by gepotidacin 1500 mg (2 x 750 mg) high shear wet granulation (HSWG) tablets orally for 3 days in each treatment period in Part 1a. There was a washout period of at least 3 days between the doses.	Gepotidacin HSWG Then Gepotidacin- R Then Gepotidacin RC Participants received gepotidacin 1500 mg (2 x 750 mg) HSWG tablets in treatment period 1 followed by gepotidacin 1500 mg (3 x 500 mg) - R capsules in treatment Period 2 followed by gepotidacin 1500 mg (2 x 750 mg) RC tablets in treatment period 3 orally for 3 days in each treatment period in Part 1a. There was a washout period of at least 3 days between the doses.	Gepotidacin-RC Then Gepotidacin HSWG Then Gepotidacin-R Participants received gepotidacin 1500 mg (2 x 750 mg) RC tablets in treatment period 1 followed by gepotidacin 1500 mg (2 x 750 mg) HSWG tablets in treatment period 2 followed by gepotidacin 1500 mg (3 x 500 mg) - R capsules in treatment period 3 for 3 days in each treatment period in Part 1a. There was a washout period of at least 3 days between the doses.	Gepotidacin 1500 mg RC Then Gepotidacin 3000 mg RC Participants received gepotidacin 1500 mg (2 x 750 mg) RC tablets in treatment period 1 followed by gepotidacin 3000 mg (4 x 750 mg) RC tablets in treatment period 2 orally for 3 days in each treatment period in Part 2. There was a washout period of at least 3 days between the doses.	Gepotidacin 1500 Then Gepotidacin 2250 Then Gepotidacin 3000 Participants received gepotidacin 1500 mg (2 x 750 mg) RC tablets - fed in treatment period 1 followed by Gepotidacin 2250 mg (3 x 750 mg) RC tablets - fed in treatment period 2 followed by Gepotidacin 2250 mg (3 x 750 mg) RC tablets - fed in treatment period 3 orally for 3 days in each treatment period in part 3. There was a washout period of at least 3 days between the doses.	Placebo Then Placebo Then Placebo Participants received matching placebo to gepotidacin 1500 mg RC tablets in treatment period 1 followed by matching placebo to gepotidacin 2250 mg in treatment period 2 followed by matching placebo to gepotidacin 2250 mg RC tablets in treatment period 3 orally for 3 days in each treatment Period in Part 3. There was a washout period of at least 3 days between the doses.
Part 1a, Period 1 (3 Days) STARTED	9	9	8	0	0	0
Part 1a, Period 1 (3 Days) COMPLETED	9	9	8	0	0	0
Part 1a, Period 1 (3 Days) NOT COMPLETED	0	0	0	0	0	0
Part 1a, Washout Period 1 (3 Days) STARTED	9	9	8	0	0	0
Part 1a, Washout Period 1 (3 Days) COMPLETED	9	9	8	0	0	0
Part 1a, Washout Period 1 (3 Days) NOT COMPLETED	0	0	0	0	0	0
Part 1a, Period 2 (3 Days) STARTED	9	9	8	0	0	0
Part 1a, Period 2 (3 Days) COMPLETED	9	9	8	0	0	0
Part 1a, Period 2 (3 Days) NOT COMPLETED	0	0	0	0	0	0
Part 1a, Washout Period 2 (3 Days) STARTED	9	9	8	0	0	0
Part 1a, Washout Period 2 (3 Days) COMPLETED	9	9	8	0	0	0
Part 1a, Washout Period 2 (3 Days) NOT COMPLETED	0	0	0	0	0	0
Part 1a, Period 3 (3 Days) STARTED	9	9	8	0	0	0
Part 1a, Period 3 (3 Days) COMPLETED	9	9	8	0	0	0
Part 1a, Period 3 (3 Days) NOT COMPLETED	0	0	0	0	0	0
Part 2, Period 1 (3 Days) STARTED	0	0	0	10	0	0
Part 2, Period 1 (3 Days) COMPLETED	0	0	0	10	0	0
Part 2, Period 1 (3 Days) NOT COMPLETED	0	0	0	0	0	0
Part 2, Washout Period 1 (3 Days) STARTED	0	0	0	10	0	0
Part 2, Washout Period 1 (3 Days) COMPLETED	0	0	0	10	0	0
Part 2, Washout Period 1 (3 Days) NOT COMPLETED	0	0	0	0	0	0
Part 2, Period 2 (3 Days) STARTED	0	0	0	10	0	0
Part 2, Period 2 (3 Days) COMPLETED	0	0	0	10	0	0
Part 2, Period 2 (3 Days) NOT COMPLETED	0	0	0	0	0	0
Part 3, Period 1 (3 Days) STARTED	0	0	0	0	10	2
Part 3, Period 1 (3 Days) COMPLETED	0	0	0	0	10	2
Part 3, Period 1 (3 Days) NOT COMPLETED	0	0	0	0	0	0
Part 3, Washout Period 1 (3 Days) STARTED	0	0	0	0	10	2
Part 3, Washout Period 1 (3 Days) COMPLETED	0	0	0	0	10	2
Part 3, Washout Period 1 (3 Days) NOT COMPLETED	0	0	0	0	0	0
Part 3, Period 2 (3 Days) STARTED	0	0	0	0	10	2
Part 3, Period 2 (3 Days) COMPLETED	0	0	0	0	10	2
Part 3, Period 2 (3 Days) NOT COMPLETED	0	0	0	0	0	0
Part 3, Washout Period 2 (3 Days) STARTED	0	0	0	0	10	2
Part 3, Washout Period 2 (3 Days) COMPLETED	0	0	0	0	9	2
Part 3, Washout Period 2 (3 Days) NOT COMPLETED	0	0	0	0	1	0
Part 3, Period 3 (3 Days) STARTED	0	0	0	0	9	2
Part 3, Period 3 (3 Days) COMPLETED	0	0	0	0	9	2
Part 3, Period 3 (3 Days) NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Gepotidacin-R Then Gepotidacin RC Then Gepotidacin HSWG Participants received gepotidacin 1500 milligrams (mg) (3 x 500 mg) (Reference \[R\]) capsules in treatment period 1 followed by gepotidacin 1500 mg (2 x 750 mg) related RC tablets in treatment period 2 followed by gepotidacin 1500 mg (2 x 750 mg) high shear wet granulation (HSWG) tablets orally for 3 days in each treatment period in Part 1a. There was a washout period of at least 3 days between the doses.	Gepotidacin HSWG Then Gepotidacin- R Then Gepotidacin RC Participants received gepotidacin 1500 mg (2 x 750 mg) HSWG tablets in treatment period 1 followed by gepotidacin 1500 mg (3 x 500 mg) - R capsules in treatment Period 2 followed by gepotidacin 1500 mg (2 x 750 mg) RC tablets in treatment period 3 orally for 3 days in each treatment period in Part 1a. There was a washout period of at least 3 days between the doses.	Gepotidacin-RC Then Gepotidacin HSWG Then Gepotidacin-R Participants received gepotidacin 1500 mg (2 x 750 mg) RC tablets in treatment period 1 followed by gepotidacin 1500 mg (2 x 750 mg) HSWG tablets in treatment period 2 followed by gepotidacin 1500 mg (3 x 500 mg) - R capsules in treatment period 3 for 3 days in each treatment period in Part 1a. There was a washout period of at least 3 days between the doses.	Gepotidacin 1500 mg RC Then Gepotidacin 3000 mg RC Participants received gepotidacin 1500 mg (2 x 750 mg) RC tablets in treatment period 1 followed by gepotidacin 3000 mg (4 x 750 mg) RC tablets in treatment period 2 orally for 3 days in each treatment period in Part 2. There was a washout period of at least 3 days between the doses.	Gepotidacin 1500 Then Gepotidacin 2250 Then Gepotidacin 3000 Participants received gepotidacin 1500 mg (2 x 750 mg) RC tablets - fed in treatment period 1 followed by Gepotidacin 2250 mg (3 x 750 mg) RC tablets - fed in treatment period 2 followed by Gepotidacin 2250 mg (3 x 750 mg) RC tablets - fed in treatment period 3 orally for 3 days in each treatment period in part 3. There was a washout period of at least 3 days between the doses.	Placebo Then Placebo Then Placebo Participants received matching placebo to gepotidacin 1500 mg RC tablets in treatment period 1 followed by matching placebo to gepotidacin 2250 mg in treatment period 2 followed by matching placebo to gepotidacin 2250 mg RC tablets in treatment period 3 orally for 3 days in each treatment Period in Part 3. There was a washout period of at least 3 days between the doses.
Part 3, Washout Period 2 (3 Days) Withdrawal by Subject	0	0	0	0	1	0

Baseline Characteristics

To Assess Bioavailability, Food Effect and Pharmacokinetics of Gepotidacin Tablets: A Phase I, Single-Dose, 2 Part Study in Healthy Subjects.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Total Participants-Part 1a n=26 Participants Participants received gepotidacin 1500 mg (3 x 500 mg) capsules, gepotidacin 1500 mg (2 x 750 mg) RC tablets and gepotidacin 1500 mg (2 x 750 mg) HSWG tablets orally in one of the 3 treatment periods in a cross-over manner. There was a washout period of at least 3 days between the doses.	Total Participants-Part 2 n=10 Participants Participants received gepotidacin 1500 mg (2 x 750 mg) RC tablets and gepotidacin 3000 mg (4 x 750 mg) RC tablets orally in one of the 2 treatment periods in a cross-over manner. There was a washout period of at least 3 days between the doses.	Total Participants- Part 3 n=12 Participants Participants received gepotidacin 1500 mg (2 x 750 mg) RC tablets - fed, gepotidacin 2250 mg (3 x 750 mg) RC tablets - fed and gepotidacin 3000 mg (4 x 750 mg) RC tablets - fed orally in one of the 3 treatment periods in a cross-over manner. There was a washout period of at least 3 days between the doses.	Total n=48 Participants Total of all reporting groups
Age, Continuous	39.5 Years STANDARD_DEVIATION 10.64 • n=5 Participants	55.6 Years STANDARD_DEVIATION 6.43 • n=7 Participants	37.8 Years STANDARD_DEVIATION 7.93 • n=5 Participants	42.5 Years STANDARD_DEVIATION 11.39 • n=4 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	8 Participants n=7 Participants	6 Participants n=5 Participants	19 Participants n=4 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants	29 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	10 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	10 Participants n=4 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	16 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	16 Participants n=4 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	0 Participants n=5 Participants	10 Participants n=7 Participants	12 Participants n=5 Participants	22 Participants n=4 Participants

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period

Population: PK Parameter Population

Blood samples for pharmacokinetic (PK) analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1a. For each sample, 3 milliliters (mL) of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. The PK Parameter Population consisted of all participants in the PK Population, for whom valid and evaluable PK parameters were derived. Statistics has been presented on geometric least square (LS) means.

Outcome measures

Outcome measures
Measure	Gepotidacin 1500 mg - R Capsules n=26 Participants Participants received gepotidacin 1500 (3 x 500) mg - R capsules orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg RC Tablets n=26 Participants Participants received gepotidacin 1500 (2 x 750) mg RC tablets orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg HSWG Tablets n=26 Participants Participants received gepotidacin 1500 mg (2 x 750 mg) HSWG tablets orally in one of the 3 treatment periods in Part 1a.	Placebo Participants received matching placebo to active tablets in the fed state in one of the 3 treatment periods in Part 3.
Area Under the Concentration-time Curve From Time 0 (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) of Plasma Gepotidacin for Part 1a	16733 hours*nanograms/milliliter Geometric Coefficient of Variation 25.7	17495 hours*nanograms/milliliter Geometric Coefficient of Variation 23.0	18646 hours*nanograms/milliliter Geometric Coefficient of Variation 24.0	—

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period

Population: PK Parameter Population

Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1a. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. Statistics has been presented on geometric LS means.

Outcome measures

Outcome measures
Measure	Gepotidacin 1500 mg - R Capsules n=26 Participants Participants received gepotidacin 1500 (3 x 500) mg - R capsules orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg RC Tablets n=26 Participants Participants received gepotidacin 1500 (2 x 750) mg RC tablets orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg HSWG Tablets n=26 Participants Participants received gepotidacin 1500 mg (2 x 750 mg) HSWG tablets orally in one of the 3 treatment periods in Part 1a.	Placebo Participants received matching placebo to active tablets in the fed state in one of the 3 treatment periods in Part 3.
Area Under the Concentration-time Curve (AUC) From Time 0 (Pre-dose) to Time of the Last Quantifiable Concentration (AUC [0-t]) of Plasma Gepotidacin for Part 1a	16409 hours*nanograms/milliliters Geometric Coefficient of Variation 26.2	17125 hours*nanograms/milliliters Geometric Coefficient of Variation 23.4	18317 hours*nanograms/milliliters Geometric Coefficient of Variation 24.1	—

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period

Population: PK Parameter Population

Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1a. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. NA indicates data was not available as this was the reference capsule the Frel of each tablet type was being compared to.

Outcome measures

Outcome measures
Measure	Gepotidacin 1500 mg - R Capsules n=26 Participants Participants received gepotidacin 1500 (3 x 500) mg - R capsules orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg RC Tablets n=26 Participants Participants received gepotidacin 1500 (2 x 750) mg RC tablets orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg HSWG Tablets n=26 Participants Participants received gepotidacin 1500 mg (2 x 750 mg) HSWG tablets orally in one of the 3 treatment periods in Part 1a.	Placebo Participants received matching placebo to active tablets in the fed state in one of the 3 treatment periods in Part 3.
Relative Bioavailability of Drug (Frel) of Plasma Gepotidacin for Part 1a	NA Ratio of AUC (0-infinity) Geometric Coefficient of Variation NA This was the reference capsule the Frel of each tablet was being compared to.	1.05 Ratio of AUC (0-infinity) Geometric Coefficient of Variation 22.3	1.11 Ratio of AUC (0-infinity) Geometric Coefficient of Variation 16.5	—

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period

Population: PK Parameter Population

Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1a. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. Statistics has been presented on geometric LS means.

Outcome measures

Outcome measures
Measure	Gepotidacin 1500 mg - R Capsules n=26 Participants Participants received gepotidacin 1500 (3 x 500) mg - R capsules orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg RC Tablets n=26 Participants Participants received gepotidacin 1500 (2 x 750) mg RC tablets orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg HSWG Tablets n=26 Participants Participants received gepotidacin 1500 mg (2 x 750 mg) HSWG tablets orally in one of the 3 treatment periods in Part 1a.	Placebo Participants received matching placebo to active tablets in the fed state in one of the 3 treatment periods in Part 3.
Maximum Observed Concentration (Cmax) Determined Directly From the Concentration Time Data of Plasma Gepotidacin for Part 1a	4648 nanograms/milliliter Geometric Coefficient of Variation 43.8	4487 nanograms/milliliter Geometric Coefficient of Variation 43.6	5349 nanograms/milliliter Geometric Coefficient of Variation 46.8	—

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period

Population: PK Parameter Population

Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1a. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher.

Outcome measures

Outcome measures
Measure	Gepotidacin 1500 mg - R Capsules n=26 Participants Participants received gepotidacin 1500 (3 x 500) mg - R capsules orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg RC Tablets n=26 Participants Participants received gepotidacin 1500 (2 x 750) mg RC tablets orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg HSWG Tablets n=26 Participants Participants received gepotidacin 1500 mg (2 x 750 mg) HSWG tablets orally in one of the 3 treatment periods in Part 1a.	Placebo Participants received matching placebo to active tablets in the fed state in one of the 3 treatment periods in Part 3.
Time to First Occurrence of Cmax (Tmax) of Plasma Gepotidacin for Part 1a	1.50 hours Interval 1.0 to 4.0	1.50 hours Interval 0.5 to 4.0	1.00 hours Interval 0.5 to 3.0	—

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period

Population: PK Parameter Population

Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1a. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher.

Outcome measures

Outcome measures
Measure	Gepotidacin 1500 mg - R Capsules n=26 Participants Participants received gepotidacin 1500 (3 x 500) mg - R capsules orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg RC Tablets n=26 Participants Participants received gepotidacin 1500 (2 x 750) mg RC tablets orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg HSWG Tablets n=26 Participants Participants received gepotidacin 1500 mg (2 x 750 mg) HSWG tablets orally in one of the 3 treatment periods in Part 1a.	Placebo Participants received matching placebo to active tablets in the fed state in one of the 3 treatment periods in Part 3.
Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) of Plasma Gepotidacin for Part 1a	0.00 hours Interval 0.0 to 0.0	0.00 hours Interval 0.0 to 0.5	0.00 hours Interval 0.0 to 0.5	—

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in each treatment period

Population: PK Parameter Population

Blood samples for PK analysis of gepotidacin were collected at Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours (Day 1), 24, 36 hours (Day 2) and 48 hours (Day 3) in Part 1a. For each sample, 3 mL of blood was drawn via an indwelling catheter and/or direct venipuncture into tubes containing ethylenediaminetetraacetate anticoagulant. PK parameters were determined from the plasma concentration-time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher.

Outcome measures

Outcome measures
Measure	Gepotidacin 1500 mg - R Capsules n=26 Participants Participants received gepotidacin 1500 (3 x 500) mg - R capsules orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg RC Tablets n=26 Participants Participants received gepotidacin 1500 (2 x 750) mg RC tablets orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg HSWG Tablets n=26 Participants Participants received gepotidacin 1500 mg (2 x 750 mg) HSWG tablets orally in one of the 3 treatment periods in Part 1a.	Placebo Participants received matching placebo to active tablets in the fed state in one of the 3 treatment periods in Part 3.
Terminal Phase Half-life (t1/2) of Plasma Gepotidacin for Part 1a	10.29 hours Geometric Coefficient of Variation 13.7	10.24 hours Geometric Coefficient of Variation 15.2	10.24 hours Geometric Coefficient of Variation 12.1	—

PRIMARY outcome

Timeframe: Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours

Population: PK Parameter Population

PK urine samples were collected at 0 (predose), 0 to 2, 2 ot 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher

Outcome measures

Outcome measures
Measure	Gepotidacin 1500 mg - R Capsules n=26 Participants Participants received gepotidacin 1500 (3 x 500) mg - R capsules orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg RC Tablets n=26 Participants Participants received gepotidacin 1500 (2 x 750) mg RC tablets orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg HSWG Tablets n=26 Participants Participants received gepotidacin 1500 mg (2 x 750 mg) HSWG tablets orally in one of the 3 treatment periods in Part 1a.	Placebo Participants received matching placebo to active tablets in the fed state in one of the 3 treatment periods in Part 3.
Total Unchanged Drug (Total Amount of Drug Excreted in Urine [Ae Total]) for Part 1a	274.925 milligrams Geometric Coefficient of Variation 28.6	286.751 milligrams Geometric Coefficient of Variation 22.2	284.510 milligrams Geometric Coefficient of Variation 30.0	—

PRIMARY outcome

Timeframe: Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours

Population: PK Parameter Population

PK urine samples were collected at 0 (pre-dose), 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher.

Outcome measures

Outcome measures
Measure	Gepotidacin 1500 mg - R Capsules n=26 Participants Participants received gepotidacin 1500 (3 x 500) mg - R capsules orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg RC Tablets n=26 Participants Participants received gepotidacin 1500 (2 x 750) mg RC tablets orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg HSWG Tablets n=26 Participants Participants received gepotidacin 1500 mg (2 x 750 mg) HSWG tablets orally in one of the 3 treatment periods in Part 1a.	Placebo Participants received matching placebo to active tablets in the fed state in one of the 3 treatment periods in Part 3.
Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Plasma Gepotidacin for Part 1a	18.329 Percentage dose of drug excreted Geometric Coefficient of Variation 28.6	19.116 Percentage dose of drug excreted Geometric Coefficient of Variation 22.2	18.968 Percentage dose of drug excreted Geometric Coefficient of Variation 30.0	—

PRIMARY outcome

Timeframe: Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours

Population: PK Parameter Population

PK urine samples were collected at 0 (pre-dose), 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher.

Outcome measures

Outcome measures
Measure	Gepotidacin 1500 mg - R Capsules n=26 Participants Participants received gepotidacin 1500 (3 x 500) mg - R capsules orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg RC Tablets n=26 Participants Participants received gepotidacin 1500 (2 x 750) mg RC tablets orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg HSWG Tablets n=26 Participants Participants received gepotidacin 1500 mg (2 x 750 mg) HSWG tablets orally in one of the 3 treatment periods in Part 1a.	Placebo Participants received matching placebo to active tablets in the fed state in one of the 3 treatment periods in Part 3.
Renal Clearance of Drug in Urine (CLr) for Part 1a	16.761 liters/hour Geometric Coefficient of Variation 21.7	16.740 liters/hour Geometric Coefficient of Variation 19.6	15.532 liters/hour Geometric Coefficient of Variation 22.3	—

PRIMARY outcome

Timeframe: Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours

Population: PK Parameter Population

PK urine samples were collected at 0 (pre-dose), 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. Only those participants available at the specific time points were analyzed (represented by n = X in the category titles).

Outcome measures

Outcome measures
Measure	Gepotidacin 1500 mg - R Capsules n=26 Participants Participants received gepotidacin 1500 (3 x 500) mg - R capsules orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg RC Tablets n=26 Participants Participants received gepotidacin 1500 (2 x 750) mg RC tablets orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg HSWG Tablets n=26 Participants Participants received gepotidacin 1500 mg (2 x 750 mg) HSWG tablets orally in one of the 3 treatment periods in Part 1a.	Placebo Participants received matching placebo to active tablets in the fed state in one of the 3 treatment periods in Part 3.
Amount of Drug Excreted in Urine in a Time Intervals for Pre-dose, 0 to 2 Hours, 2 to 4 Hours, 4 to 6 Hours, 6 to 8 Hours, 8 to 12 Hours, 12 to 24 Hours, 24 to 36 Hours, and 36 to 48 Hours (Ae [t1-t2]) for Part 1a Ae (0-2), n=26,25,26	65.817 milligrams Geometric Coefficient of Variation 95.1	60.915 milligrams Geometric Coefficient of Variation 102.9	85.584 milligrams Geometric Coefficient of Variation 67.7	—
Amount of Drug Excreted in Urine in a Time Intervals for Pre-dose, 0 to 2 Hours, 2 to 4 Hours, 4 to 6 Hours, 6 to 8 Hours, 8 to 12 Hours, 12 to 24 Hours, 24 to 36 Hours, and 36 to 48 Hours (Ae [t1-t2]) for Part 1a Ae (2-4),n=26,24,25	72.734 milligrams Geometric Coefficient of Variation 67.3	77.650 milligrams Geometric Coefficient of Variation 33.6	67.419 milligrams Geometric Coefficient of Variation 72.0	—
Amount of Drug Excreted in Urine in a Time Intervals for Pre-dose, 0 to 2 Hours, 2 to 4 Hours, 4 to 6 Hours, 6 to 8 Hours, 8 to 12 Hours, 12 to 24 Hours, 24 to 36 Hours, and 36 to 48 Hours (Ae [t1-t2]) for Part 1a Ae (4-6),n=25,25,26	36.019 milligrams Geometric Coefficient of Variation 44.2	45.313 milligrams Geometric Coefficient of Variation 61.1	39.361 milligrams Geometric Coefficient of Variation 39.1	—
Amount of Drug Excreted in Urine in a Time Intervals for Pre-dose, 0 to 2 Hours, 2 to 4 Hours, 4 to 6 Hours, 6 to 8 Hours, 8 to 12 Hours, 12 to 24 Hours, 24 to 36 Hours, and 36 to 48 Hours (Ae [t1-t2]) for Part 1a Ae (6-8),n=25,26,26	22.817 milligrams Geometric Coefficient of Variation 37.4	26.061 milligrams Geometric Coefficient of Variation 24.9	22.755 milligrams Geometric Coefficient of Variation 28.7	—
Amount of Drug Excreted in Urine in a Time Intervals for Pre-dose, 0 to 2 Hours, 2 to 4 Hours, 4 to 6 Hours, 6 to 8 Hours, 8 to 12 Hours, 12 to 24 Hours, 24 to 36 Hours, and 36 to 48 Hours (Ae [t1-t2]) for Part 1a Ae (8-12),n=26,26,26	21.515 milligrams Geometric Coefficient of Variation 57.3	25.609 milligrams Geometric Coefficient of Variation 27.7	16.590 milligrams Geometric Coefficient of Variation 75.5	—
Amount of Drug Excreted in Urine in a Time Intervals for Pre-dose, 0 to 2 Hours, 2 to 4 Hours, 4 to 6 Hours, 6 to 8 Hours, 8 to 12 Hours, 12 to 24 Hours, 24 to 36 Hours, and 36 to 48 Hours (Ae [t1-t2]) for Part 1a Ae (12-24),n=26,26,26	19.224 milligrams Geometric Coefficient of Variation 60.4	22.536 milligrams Geometric Coefficient of Variation 26.9	19.432 milligrams Geometric Coefficient of Variation 32.9	—
Amount of Drug Excreted in Urine in a Time Intervals for Pre-dose, 0 to 2 Hours, 2 to 4 Hours, 4 to 6 Hours, 6 to 8 Hours, 8 to 12 Hours, 12 to 24 Hours, 24 to 36 Hours, and 36 to 48 Hours (Ae [t1-t2]) for Part 1a Ae (24-36),n=26,26,26	8.145 milligrams Geometric Coefficient of Variation 35.0	9.787 milligrams Geometric Coefficient of Variation 27.8	8.185 milligrams Geometric Coefficient of Variation 44.4	—
Amount of Drug Excreted in Urine in a Time Intervals for Pre-dose, 0 to 2 Hours, 2 to 4 Hours, 4 to 6 Hours, 6 to 8 Hours, 8 to 12 Hours, 12 to 24 Hours, 24 to 36 Hours, and 36 to 48 Hours (Ae [t1-t2]) for Part 1a Ae (36-48),n=26,26,26	4.633 milligrams Geometric Coefficient of Variation 31.4	4.517 milligrams Geometric Coefficient of Variation 57.7	4.319 milligrams Geometric Coefficient of Variation 41.0	—

PRIMARY outcome

Timeframe: Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours.

Population: PK Parameter Population

PK urine samples were collected at 0 (pre-dose), 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher

Outcome measures

Outcome measures
Measure	Gepotidacin 1500 mg - R Capsules n=26 Participants Participants received gepotidacin 1500 (3 x 500) mg - R capsules orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg RC Tablets n=26 Participants Participants received gepotidacin 1500 (2 x 750) mg RC tablets orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg HSWG Tablets n=26 Participants Participants received gepotidacin 1500 mg (2 x 750 mg) HSWG tablets orally in one of the 3 treatment periods in Part 1a.	Placebo Participants received matching placebo to active tablets in the fed state in one of the 3 treatment periods in Part 3.
Area Under the Urine Concentration-time Curve Over Time 0 (Pre-dose) to 12 Hours (AUC [0-12]) for Part 1a	1904 micrograms*hours/milliliter Geometric Coefficient of Variation 82.7	1948 micrograms*hours/milliliter Geometric Coefficient of Variation 61.2	2156 micrograms*hours/milliliter Geometric Coefficient of Variation 74.8	—

PRIMARY outcome

Timeframe: Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours

Population: PK Parameter Population

PK urine samples were collected at 0 (pre-dose), 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher

Outcome measures

Outcome measures
Measure	Gepotidacin 1500 mg - R Capsules n=26 Participants Participants received gepotidacin 1500 (3 x 500) mg - R capsules orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg RC Tablets n=26 Participants Participants received gepotidacin 1500 (2 x 750) mg RC tablets orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg HSWG Tablets n=262 Participants Participants received gepotidacin 1500 mg (2 x 750 mg) HSWG tablets orally in one of the 3 treatment periods in Part 1a.	Placebo Participants received matching placebo to active tablets in the fed state in one of the 3 treatment periods in Part 3.
Area Under the Urine Concentration-time Curve Over Time 0 (Pre-dose) to 24 Hours (AUC [0-24]) After Dosing for Part 1a	2373 micrograms*hours/milliliter Geometric Coefficient of Variation 74.9	2464 micrograms*hours/milliliter Geometric Coefficient of Variation 56.3	2599 micrograms*hours/milliliter Geometric Coefficient of Variation 69.0	—

PRIMARY outcome

Timeframe: Pre-dose, 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, and 36 to 48 hours

Population: PK Parameter Population.

PK urine samples were collected at 0 (pre-dose), 0 to 2, 2 to 4, 4 to 6, 6 to 8, 8 to 12, 12 to 24, 24 to 36, 36 to 48 hours. PK parameters were determined from the urine concentration- time data and were calculated by standard non-compartmental analysis according to current working practices and using Phoenix WinNonlin Version 6.2.1 or higher. Only those participants with data available at the indicated time point were analyzed.

Outcome measures

Outcome measures
Measure	Gepotidacin 1500 mg - R Capsules n=23 Participants Participants received gepotidacin 1500 (3 x 500) mg - R capsules orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg RC Tablets n=26 Participants Participants received gepotidacin 1500 (2 x 750) mg RC tablets orally in one of the 3 treatment periods for 3 days in Part 1a.	Gepotidacin 1500 mg HSWG Tablets n=24 Participants Participants received gepotidacin 1500 mg (2 x 750 mg) HSWG tablets orally in one of the 3 treatment periods in Part 1a.	Placebo Participants received matching placebo to active tablets in the fed state in one of the 3 treatment periods in Part 3.
Area Under the Urine Concentration-time Curve Over Time 0 (Pre-dose) to 48 Hours (AUC [0-48]) After Dosing for Part 1a	2597 micrograms*hours/milliliter Geometric Coefficient of Variation 69.5	2725 micrograms*hours/milliliter Geometric Coefficient of Variation 54.4	2768 micrograms*hours/milliliter Geometric Coefficient of Variation 64.0	—

SECONDARY outcome

Timeframe: Up to 11 days

Population: Safety Population

AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant.