Drug-drug Interaction Study of Gepotidacin
Study Details
Study Description
Brief Summary
This study is a drug-drug interaction (DDI), pharmacokinetics (PK), safety and tolerability study in adult healthy participants, including Japanese cohort. This study is designed to assess co-administration of probe substrates with gepotidacin in study cohorts 1 to 3 and establishing PK and safety in Japanese participants in cohort 4. Food effect will also be evaluated in cohort 4.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg This is a fixed sequence (Sequence AB) cohort. Participants will receive gepotidacin 1500 milligrams (mg) single dose (SD) on Day 1 of Period 1 (Treatment A); and Cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 and gepotidacin 1500 mg single dose (Treatment B). Gepotidacin will be administered 1 hour after the first dose of cimetidine on Day 2 of Period 2. There will be a washout of at least 3 days between Treatment A and Treatment B, and a follow-up visit 5 to 7 days after the last dose of cimetidine. |
Drug: Gepotidacin
Gepotidacin tablets will be available as unit dose strength 750 mg and will be administered orally.
Other Names:
Drug: Cimetidine
Cimetidine tablets will be available as unit dose strength 400 mg and will be administered orally.
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Experimental: Cohort 2: Gepotidacin 1500 mg + Rifampicin 600 mg This is a fixed sequence (Sequence CDE) cohort. Participants will receive gepotidacin 1500 mg single dose on Day 1 of Period 1 (Treatment C), rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7 of Period 2, to elicit maximal enzyme induction) (Treatment D); and gepotidacin 1500 mg single dose administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 (Treatment E). There will be a washout of at least 3 days between Treatment C and Treatment D, and a follow-up visit 7 to 10 days after the last dose of rifampicin. |
Drug: Gepotidacin
Gepotidacin tablets will be available as unit dose strength 750 mg and will be administered orally.
Other Names:
Drug: Rifampicin
Rifampicin Capsules will be available as unit dose strength 300 mg and will be administered orally.
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Experimental: Cohort 3: Digoxin 0.5mg+Midazolam 2mg then Gepotidacin 3000mg Participants will receive digoxin 0.5 mg and midazolam 2 mg (Treatment F) in Period 1 on Day 1 then gepotidacin two 3000 mg doses (given 12 hours apart) co-administered with digoxin 0.5 mg and midazolam 2 mg in Period 2 on Day 1, with the 2 probe drugs administered with the second daily dose of gepotidacin only (Treatment G). There will be a washout of at least 10 days between treatments. In Sequence 2, these regimens are reversed. A follow-up visit will occur 7 to 10 days after the last dose of study intervention in Period 2. |
Drug: Gepotidacin
Gepotidacin tablets will be available as unit dose strength 750 mg and will be administered orally.
Other Names:
Drug: Midazolam
Midazolam oral syrup 2 milligrams per milliliter (mg/mL) will be available to be administered orally.
Drug: Digoxin
Digoxin tablets will be available as unit dose strength 0.25 mg and will be administered orally.
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Experimental: Cohort 3: Gepotidacin 3000mg then Digoxin 0.5mg+Midazolam 2mg Participants will receive gepotidacin two 3000 mg doses (given 12 hours apart) co-administered with digoxin 0.5 mg and midazolam 2 mg in Period 1 on Day 1, with the 2 probe drugs administered with the second daily dose of gepotidacin only (Treatment G) followed by digoxin 0.5 mg and midazolam 2 mg (Treatment F) in Period 2 on Day 1. A follow-up visit will occur 7 to 10 days after the last dose of study intervention in Period 2. |
Drug: Gepotidacin
Gepotidacin tablets will be available as unit dose strength 750 mg and will be administered orally.
Other Names:
Drug: Midazolam
Midazolam oral syrup 2 milligrams per milliliter (mg/mL) will be available to be administered orally.
Drug: Digoxin
Digoxin tablets will be available as unit dose strength 0.25 mg and will be administered orally.
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Experimental: Cohort 4: Gepotidacin 1500 mg fed then fasted then 3000 mg fed Cohort 4 will include Japanese participants. Participants will receive a single dose of gepotidacin 1500 mg under fed conditions in Period 1 (Treatment H), then a single dose of gepotidacin 1500 mg under fasted conditions in Period 2 (Treatment I), followed by two doses of gepotidacin up to 3000 mg (given 12 hours apart) under fed conditions in Period 3 (Treatment J). There will be a washout of at least 3 days between each treatment, and a follow-up visit 5 to 7 days after the last dose of gepotidacin. |
Drug: Gepotidacin
Gepotidacin tablets will be available as unit dose strength 750 mg and will be administered orally.
Other Names:
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Experimental: Cohort 4: Gepotidacin 1500 mg fasted then fed then 3000 mg fed Cohort 4 will include Japanese participants. Participants will receive a single dose of gepotidacin 1500 mg under fasted conditions in Period 1 (Treatment I), then a single dose of gepotidacin 1500 mg under fed conditions in Period 2 (Treatment H), followed by two doses of gepotidacin up to 3000 mg (given 12 hours apart) under fed conditions in Period 3 (Treatment J). There will be a washout of at least 3 days between each treatment, and a follow-up visit 5 to 7 days after the last dose of gepotidacin. |
Drug: Gepotidacin
Gepotidacin tablets will be available as unit dose strength 750 mg and will be administered orally.
Other Names:
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Placebo Comparator: Cohort 4: Placebo fed then fasted then fed Cohort 4 will include Japanese participants. Participants will receive a single dose of placebo under fed conditions in Period 1, then a single dose of placebo under fasted conditions in Period 2, followed by two doses of placebo (given 12 hours apart) under fed conditions in Period 3. There will be a washout of at least 3 days between each period, and a follow-up visit 5 to 7 days after the last dose of placebo. |
Other: Placebo matching to gepotidacin
Placebo matching to gepotidacin tablets will be administered orally.
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Outcome Measures
Primary Outcome Measures
- Cohort 1: Maximum Observed Concentration (Cmax) of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric least square (LS) mean and 90 percent (%) confidence interval (CI) of the geometric LS means have been presented.
- Cohort 1: Time to Reach Maximum Observed Concentration (Tmax) of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 1: Terminal Phase Half-life (t1/2) of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
- Cohort 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
- Cohort 1: AUC From Time 0 (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
- Cohort 2: Cmax of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
- Cohort 2: Lag Time Before Observation of Drug Concentrations (Tlag) of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 2: Tmax of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 2: AUC(0-t) of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
- Cohort 2: AUC(0-infinity) of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 3: Cmax of Digoxin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 3: Tlag of Digoxin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis.
- Cohort 3: Tmax of Digoxin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis.
- Cohort 3: AUC(0-t) of Digoxin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 3: AUC(0-infinity) of Digoxin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 3: Cmax of Midazolam in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 3: Tlag of Midazolam in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis.
- Cohort 3: Tmax of Midazolam in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis.
- Cohort 3: AUC(0-t) of Midazolam in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 3: AUC(0-infinity) of Midazolam in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 24 Hours Post-dose (AUC[0-24]) of Gepotidacin Following Single Dose of 1500 mg in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 48 Hours Post-dose (AUC[0-48]) of Gepotidacin Following Single Dose of 1500 mg in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: AUC From Time 0 (Predose) to Time Tau (AUC[0-tau]) of Gepotidacin in Plasma After the First Dose of 3000 Mg-Fed State [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Evening Dose)-Fed State [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: Accumulation Ratio Based on Cmax (RoCmax) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose.
- Cohort 4: Accumulation Ratio Based on AUC(0-tau) (RoAUC) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) after the second dose, where 0 is the timepoint prior to second dose, divided by AUC(0-tau) after the first dose, where 0 is the predose timepoint prior to the first dose.
- Cohort 4: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24 Hours post-dose in Treatment Period 3]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48 Hours post-dose in Treatment Period 3]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE) [Up to 22 days]
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.
- Cohort 4: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to 22 days]
Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, Erythrocyte Mean Corpuscular Hemoglobin (MCH), Erythrocyte Mean Corpuscular Volume (MCV), Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose laboratory (lab) value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 (%). High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
- Cohort 4: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to 22 days]
Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase (Alk Phos), Aspartate Aminotransferase (AST), Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, Blood Urea Nitrogen (BUN). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
- Cohort 4: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to 22 days]
Urine samples were collected at indicated time points for the analysis of urinalysis parameters including potential of hydrogen (pH) of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
- Cohort 4: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to 22 days]
Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
- Cohort 4: Number of Participants With Any Increase in Maximum Post-Baseline Electrocardiogram (ECG) Parameter Corrected QT (QTc) Interval [Up to 22 days]
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the Bazett formula (QTcB) Interval and corrected QT interval using the Fridericia formula (QTcF) Interval has been reported.
- Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 4: Tlag of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
Secondary Outcome Measures
- Cohort 1: AUC (0-24) of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 1: AUC(0-48) of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 1: Tlag of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 1: Apparent Volume of Distribution (Vz/F) of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 1: Apparent Oral Clearance (CL/F) of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 1: Total Unchanged Drug (Ae Total) of Gepotidacin in Urine [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 1: AUC(0-24) of Gepotidacin in Urine [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours Post-dose in each Treatment periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
- Cohort 1: AUC(0-48) of Gepotidacin in Urine [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
- Cohort 1: Renal Clearance (CLr) of Gepotidacin [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented.
- Cohort 1: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin [0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.
- Cohort 1: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 percent (%).
- Cohort 1: Number of Participants With SAE and Non-SAE [Up to 17 days]
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.
- Cohort 1: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to 17 days]
Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 %. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
- Cohort 1: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to 17 days]
Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
- Cohort 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to 17 days]
Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
- Cohort 1: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to 17 days]
Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
- Cohort 1: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval [Up to 17 days]
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported.
- Cohort 2: AUC(0-24) of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 2: AUC(0-48) of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 2: T1/2 of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 2: Vz/F of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 2: CL/F of Gepotidacin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 2: Ae Total of Gepotidacin in Urine [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 2: AUC(0-24) of Gepotidacin in Urine [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 2: AUC(0-48) of Gepotidacin in Urine [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 2: CLr of Gepotidacin [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 2: Ae(t1-t2) of Gepotidacin [0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.
- Cohort 2: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %.
- Cohort 2: Number of Participants With SAE and Non-SAE [Up to 26 days]
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.
- Cohort 2: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to 26 days]
Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
- Cohort 2: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to 26 days]
Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
- Cohort 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to 26 days]
Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
- Cohort 2: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to 26 days]
Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
- Cohort 2: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval [Up to 26 days]
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported.
- Cohort 3: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose) [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 3: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose) [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 3: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose) [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 3: AUC(0-tau) of Gepotidacin in Plasma First Dose of 3000 mg (First Dose) [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 3: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose) [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 3: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose) [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 3: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose) [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 3: RoCmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose) [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose.
- Cohort 3: RoAUC of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose) [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) after the second dose, where 0 is the timepoint prior to second dose, divided by AUC(0-tau) after the first dose, where 0 is the predose timepoint prior to the first dose.
- Cohort 3: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose) [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 3: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose) [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 3: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose) [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 3: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose) [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 3: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose) [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 3: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose+ Second Dose) [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 3: Minimum Observed Concentration (Cmin) of Digoxin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 3: T1/2 of Digoxin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 3: Vz/F of Digoxin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 3: CL/F of Digoxin in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 3: Cmin of Midazolam in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 3: T1/2 of Midazolam in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 3: Vz/F of Midazolam in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 3: CL/F of Midazolam in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented.
- Cohort 3: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose ) [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.
- Cohort 3: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose) [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.
- Cohort 3: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose) [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 3: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose) [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 3: AUC (0-48) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose) [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 3: Percentage of the Given Dose of Drug Excreted in Urine (fe%) Following Two 3000 mg Doses of Gepotidacin (First Dose + Second Dose ) [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %.
- Cohort 3: CLr of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose) [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 3: Number of Participants With SAE and Non-SAE [Up to 30 days]
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment.
- Cohort 3: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to 30 days]
Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
- Cohort 3: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to 30 days]
Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
- Cohort 3: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to 30 days]
Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
- Cohort 3: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline [Up to 30 days]
Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment.
- Cohort 3: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval [Up to 30 days]
A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported.
- Cohort 4: T1/2 of Gepotidacin Following Single Dose of 1500 mg in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: Vz/F of Gepotidacin Following Single Dose of 1500 mg in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: CL/F of Gepotidacin Following Single Dose of 1500 mg in Plasma [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)-Fed State [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose )-Fed State [Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3]
Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: Ae Total of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.
- Cohort 4: Ae(t1-t2) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.
- Cohort 4: AUC(0-24) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: AUC(0-48) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) for Gepotidacin 1500 mg Under Fed Condition [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100%.
- Cohort 4: CLr of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.
- Cohort 4: Ae(t1-t2) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.
- Cohort 4: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours post-dose in Treatment Period 3]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: AUC(0-48) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours post-dose in Treatment Period 3]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
- Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin Following Two 3000 mg Doses-Fed State [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %.
- Cohort 4: CLr of Gepotidacin Following Two 3000 mg Dose-Fed State [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3]
Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis.
Other Outcome Measures
- Cohort 4: AUC(0-tau) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine [Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2]
Urine samples were collected at indicated time points. AUC(0-tau) can be calculated only for multiple doses and not for single dose as tau refers to the dosing interval. Hence, AUC(0-tau) could not be calculated for Gepotidacin 1500 mg single dose as mentioned in Reporting and Analysis Plan. The results for this outcome measure will never be posted.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Participant must be greater than or equal to (>=) 18 to less than or equal to (=<) 50 years of age inclusive, at the time of signing the informed consent.
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Participants who are healthy as determined by the investigator or medically qualified designee based on medical evaluation including medical history, physical examination, clinical laboratory tests, vital sign measurements, and 12-lead ECG results. A participant with clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the investigator feels and documents that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
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Additional inclusion criteria for Japanese participants (Cohort 4): The participant is a non-naturalized Japanese citizen and holds a Japanese passport (current or expired).
The participant has/had 2 Japanese parents and 4 Japanese grandparents who are/were all non-naturalized Japanese citizens, as confirmed by interview.
The participant has been living outside of Japan for up to 10 years as confirmed by interview.
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Participants have a body weight >=40 kilograms (kg) and body mass index within the range 18.5 to 32.0 kilograms per square meter (kg/m^2) (inclusive).
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Male and/or female: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies: Is a woman of non-childbearing potential or Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of <1 percent (%), for at least 30 days prior to dosing until completion of the follow-up Visit. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention.
A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) before the first dose of study intervention and for women not on effective contraception at least 14 days prior to baseline visit.
The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
Exclusion Criteria:
-
Clinically significant abnormality in the past medical history or at the screening physical examination that in the investigator's opinion may place the participant at risk or interfere with the outcome variables of the study. This includes, but is not limited to, history or current cardiac, hepatic, renal, neurologic, gastro-intestinal (GI), respiratory, hematologic, or immunologic disease.
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Any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study intervention, or any other condition that may place the participant at risk, in the opinion of the investigator.
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Female participant has a positive pregnancy test result or is lactating at Screening or upon admission to the clinic.
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Positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Note: Testing will be performed according to site procedures.
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Within 2 months before Screening, either a confirmed history of Clostridium difficile (C. difficile) diarrhea infection or a past positive of C. difficile toxin test.
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Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
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History of drug and/or alcohol abuse within 6 months before Screening, as determined by the investigator, or has a positive drug screen at Screening or upon admission to the clinic.
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History of sensitivity/hypersensitivity to any of the study drugs, components thereof, or a history of drug or other allergy that, in the opinion of the Investigator or GlaxoSmithKline (GSK) Medical Monitor contraindicates their participation.
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Cohort 2 Only: Participant is a contact lens wearer who is unable or unwilling to wear glasses for the duration of the study and for 5 half-lives after the last dose of rifampicin.
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Use of any systemic antibiotic within 30 days of screening.
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Participants must abstain from taking prescription or non-prescription drugs (except for hormonal contraceptives and/or acetaminophen at doses of <=2 grams/day), vitamins, and dietary or herbal supplements, within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to study intervention until completion of the follow-up Visit, unless, in the opinion of the investigator and Sponsor, the medication will not interfere with the study. Any exceptions will be discussed with the Sponsor or Medical Monitor on a case-by-case basis and the reasons will be documented.
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Previous exposure to gepotidacin.
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Participant has participated in a clinical trial and has received an investigational product (IP) prior to gepotidacin administration within 30 days, 5 half-lives, or twice the duration of the biological effect of IP (whichever is longer).
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Past participation in this clinical study.
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Baseline corrected QT interval using the Fridericia formula (QTcF) of >450 milliseconds (msec) at Screening or Check-in.
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Presence of hepatitis B surface antigen or positive hepatitis C antibody test result at Screening or within 3 months prior to starting study intervention.
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Alanine aminotransferase (ALT) >1.5 times upper limit of normal (ULN) at Screening or Check-in.
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Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at Screening or Check-in.
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History of any kidney disease or current or chronic history of mild impaired renal function as indicated by an estimated creatinine clearance <=90 milliliters per minute (mL/min).
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A positive test for human immunodeficiency virus (HIV) antibody.
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History of regular alcohol consumption within 6 months of Screening defined as an average weekly intake of >21 units (or an average daily intake of >3 units) for males or an average weekly intake of >14 units (or an average daily intake >2 units) for females. One unit is equivalent to 270 mL of full strength beer, 470 mL of light beer, 30 mL of spirits, or 100 mL of wine.
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Cohort 3 Only: Digoxin-related exclusions include the following at Screening:
Serum potassium >5.5 milliequivalent per liter (mEq/L) or < 3.6 mEq/L Serum magnesium <1.6 milligrams per deciliter (mg/dL) Serum calcium (total) <8.5 mg/dL History of hypersensitivity to digoxin or other digitalis glycosides Any clinically relevant abnormality on 12-lead ECG at Screening or Check-in.
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Participant has donated blood in excess of 500 mL within 12 weeks prior to dosing or participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56-day period.
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Participant is unable to comply with all study procedures, in the opinion of the investigator.
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Participant should not participate in the study, in the opinion of the investigator or Sponsor.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | GSK Investigational Site | Las Vegas | Nevada | United States | 89113 |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
More Information
Publications
None provided.- 213678
Study Results
Participant Flow
Recruitment Details | This study was conducted at a single center in the United States and designed to assess co-administration of probe substrates with gepotidacin in study Cohorts 1 to 3 and establishing pharmacokinetics and safety in a Japanese cohort in Cohort 4. |
---|---|
Pre-assignment Detail | A total of 64 participants (14 in Cohort 1, 17 in Cohort 2, 19 in Cohort 3 and 14 participants in Cohort 4) were enrolled in the study. |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mg | Cohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + Rifampicin | Cohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + Midazolam | Cohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+Midazolam | Cohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg Fed | Cohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg Fed | Cohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed |
---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 milligrams (mg) on Day 1 of Period 1 followed by a washout of at least 3 days. In Period 2, participants were administered with cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2. Participants had a follow-up of 7 days after the last dose of cimetidine. | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 followed by a washout of at least 3 days. In Period 2, participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) along with a single dose of gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2. Participants had a follow-up of 10 days after the last dose of rifampicin. | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 followed by a washout of 10 days. In Period 2, participants were administered with two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 2. Participants had a follow-up of 10 days after the last dose of study treatment in Period 2. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 followed by a washout of 10 days. In Period 2, participants were administered with digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 2. Participants had a follow-up of 10 days after the last dose of study treatment in Period 2. | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 followed by a washout of 3 days . In Period 2, participants were administered with a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 2 followed by a washout of 3 days. In Period 3, participants were administered with two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3. Participants had a follow-up of 7 days after the last dose of gepotidacin. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 followed by a a washout of 3 days. In Period 2, participants were administered with a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 2 followed by a washout of 3 days. In Period 3, participants were administered with two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3. Participants had a follow-up of 7 days after the last dose of gepotidacin. | Japanese participants received a single dose of placebo matching gepotidacin under fed conditions on Day 1 of Period 1 followed by a a washout of 3 days. In Period 2, participants were administered with a single dose of placebo matching gepotidacin under fasted conditions on Day 1 of Period 2, followed by a washout of 3 days. In Period 3, participants were administered with two doses of placebo matching gepotidacin (given 12 hours apart) under fed conditions on Day 1 of Period 3. Participants had a follow-up of 7 days. |
Period Title: Cohort1:Treatment Period 1(Up to 3 Days) | |||||||
STARTED | 14 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 13 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Cohort1:Treatment Period 1(Up to 3 Days) | |||||||
STARTED | 13 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 13 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Cohort1:Treatment Period 1(Up to 3 Days) | |||||||
STARTED | 13 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 13 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Cohort1:Treatment Period 1(Up to 3 Days) | |||||||
STARTED | 13 | 0 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 13 | 0 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Cohort1:Treatment Period 1(Up to 3 Days) | |||||||
STARTED | 0 | 17 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 0 | 17 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Cohort1:Treatment Period 1(Up to 3 Days) | |||||||
STARTED | 0 | 17 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 0 | 17 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Cohort1:Treatment Period 1(Up to 3 Days) | |||||||
STARTED | 0 | 17 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 0 | 14 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 3 | 0 | 0 | 0 | 0 | 0 |
Period Title: Cohort1:Treatment Period 1(Up to 3 Days) | |||||||
STARTED | 0 | 14 | 0 | 0 | 0 | 0 | 0 |
COMPLETED | 0 | 14 | 0 | 0 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Cohort1:Treatment Period 1(Up to 3 Days) | |||||||
STARTED | 0 | 0 | 10 | 9 | 0 | 0 | 0 |
COMPLETED | 0 | 0 | 9 | 9 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Period Title: Cohort1:Treatment Period 1(Up to 3 Days) | |||||||
STARTED | 0 | 0 | 9 | 9 | 0 | 0 | 0 |
COMPLETED | 0 | 0 | 9 | 9 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Cohort1:Treatment Period 1(Up to 3 Days) | |||||||
STARTED | 0 | 0 | 9 | 9 | 0 | 0 | 0 |
COMPLETED | 0 | 0 | 9 | 9 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Cohort1:Treatment Period 1(Up to 3 Days) | |||||||
STARTED | 0 | 0 | 9 | 9 | 0 | 0 | 0 |
COMPLETED | 0 | 0 | 9 | 9 | 0 | 0 | 0 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Cohort1:Treatment Period 1(Up to 3 Days) | |||||||
STARTED | 0 | 0 | 0 | 0 | 6 | 5 | 3 |
COMPLETED | 0 | 0 | 0 | 0 | 6 | 5 | 3 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Cohort1:Treatment Period 1(Up to 3 Days) | |||||||
STARTED | 0 | 0 | 0 | 0 | 6 | 5 | 3 |
COMPLETED | 0 | 0 | 0 | 0 | 6 | 5 | 3 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Cohort1:Treatment Period 1(Up to 3 Days) | |||||||
STARTED | 0 | 0 | 0 | 0 | 6 | 5 | 3 |
COMPLETED | 0 | 0 | 0 | 0 | 6 | 5 | 3 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Cohort1:Treatment Period 1(Up to 3 Days) | |||||||
STARTED | 0 | 0 | 0 | 0 | 6 | 5 | 3 |
COMPLETED | 0 | 0 | 0 | 0 | 6 | 5 | 3 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Cohort1:Treatment Period 1(Up to 3 Days) | |||||||
STARTED | 0 | 0 | 0 | 0 | 6 | 5 | 3 |
COMPLETED | 0 | 0 | 0 | 0 | 6 | 5 | 3 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Period Title: Cohort1:Treatment Period 1(Up to 3 Days) | |||||||
STARTED | 0 | 0 | 0 | 0 | 6 | 5 | 3 |
COMPLETED | 0 | 0 | 0 | 0 | 6 | 5 | 3 |
NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline Characteristics
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg/Cimetidine + Gepotidacin 1500 mg | Cohort 2: Gepotidacin 1500 mg/Gepotidacin 1500 mg + Rifampicin | Cohort 3: Digoxin+Midazolam/Gepotidacin 3000 mg + Digoxin + Midazolam | Cohort 3: Gepotidacin 3000 mg + Digoxin + Midazolam/Digoxin+Midazolam | Cohort 4:Gepotidacin 1500 mg Fed/Gepotidacin 1500 mg Fasted/Gepotidacin 3000 mg Fed | Cohort 4:Gepotidacin 1500 mg Fasted/Gepotidacin 1500 mg Fed/Gepotidacin 3000 mg Fed | Cohort 4: Placebo Fed/ Placebo Fasted/ Placebo Fed | Total |
---|---|---|---|---|---|---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 milligrams (mg) on Day 1 of Period 1 followed by a washout of at least 3 days. In Period 2, participants were administered with cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2. Participants had a follow-up of 7 days after the last dose of cimetidine. | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 followed by a washout of at least 3 days. In Period 2, participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) along with a single dose of gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2. Participants had a follow-up of 10 days after the last dose of rifampicin. | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 followed by a washout of 10 days. In Period 2, participants were administered with two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 2. Participants had a follow-up of 10 days after the last dose of study treatment in Period 2. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 followed by a washout of 10 days. In Period 2, participants were administered with digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 2. Participants had a follow-up of 10 days after the last dose of study treatment in Period 2. | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 followed by a washout of 3 days . In Period 2, participants were administered with a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 2 followed by a washout of 3 days. In Period 3, participants were administered with two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3. Participants had a follow-up of 7 days after the last dose of gepotidacin. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 followed by a a washout of 3 days. In Period 2, participants were administered with a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 2 followed by a washout of 3 days. In Period 3, participants were administered with two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3. Participants had a follow-up of 7 days after the last dose of gepotidacin. | Japanese participants received a single dose of placebo matching gepotidacin under fed conditions on Day 1 of Period 1 followed by a a washout of 3 days. In Period 2, participants were administered with a single dose of placebo matching gepotidacin under fasted conditions on Day 1 of Period 2, followed by a washout of 3 days. In Period 3, participants were administered with two doses of placebo matching gepotidacin (given 12 hours apart) under fed conditions on Day 1 of Period 3. Participants had a follow-up of 7 days. | Total of all reporting groups |
Overall Participants | 14 | 17 | 10 | 9 | 6 | 5 | 3 | 64 |
Age, Customized (Count of Participants) | ||||||||
<18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
18-64 years |
14
100%
|
17
100%
|
10
100%
|
9
100%
|
6
100%
|
5
100%
|
3
100%
|
64
100%
|
>=65 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Sex: Female, Male (Count of Participants) | ||||||||
Female |
7
50%
|
4
23.5%
|
3
30%
|
5
55.6%
|
2
33.3%
|
2
40%
|
2
66.7%
|
25
39.1%
|
Male |
7
50%
|
13
76.5%
|
7
70%
|
4
44.4%
|
4
66.7%
|
3
60%
|
1
33.3%
|
39
60.9%
|
Race/Ethnicity, Customized (Count of Participants) | ||||||||
BLACK OR AFRICAN AMERICAN |
8
57.1%
|
7
41.2%
|
6
60%
|
5
55.6%
|
0
0%
|
0
0%
|
0
0%
|
26
40.6%
|
NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER |
1
7.1%
|
1
5.9%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
3.1%
|
WHITE |
4
28.6%
|
5
29.4%
|
4
40%
|
4
44.4%
|
0
0%
|
0
0%
|
0
0%
|
17
26.6%
|
BLACK OR AFRICAN AMERICAN/WHITE |
1
7.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.6%
|
ASIAN(A)/BLACK OR AFRICAN AMERICAN |
0
0%
|
1
5.9%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.6%
|
JAPANESE HERITAGE(H)/EAST A H/SOUTH EAST A H |
0
0%
|
2
11.8%
|
0
0%
|
0
0%
|
6
100%
|
5
100%
|
3
100%
|
16
25%
|
AMERICAN INDIAN OR ALASKA NATIVE/WHITE |
0
0%
|
1
5.9%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
1.6%
|
Outcome Measures
Title | Cohort 1: Maximum Observed Concentration (Cmax) of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric least square (LS) mean and 90 percent (%) confidence interval (CI) of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population comprised of all participants in the Pharmacokinetic Population (received at least 1 dose of study intervention and had at least 1 non-missing plasma or urine pharmacokinetic concentration) who received study intervention for whom valid and evaluable plasma or urine pharmacokinetic parameters were derived. |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 14 | 13 |
Geometric Least Squares Mean (90% Confidence Interval) [Micrograms per milliliter] |
4.817
|
4.548
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS Mean |
Estimated Value | 0.944 | |
Confidence Interval |
(2-Sided) 90% 0.753 to 1.184 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 1: Time to Reach Maximum Observed Concentration (Tmax) of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 14 | 13 |
Median (Full Range) [Hours] |
2.500
|
2.500
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
Estimated Value | -0.250 | |
Confidence Interval |
(2-Sided) 90% -0.750 to 0.742 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate. |
Title | Cohort 1: Terminal Phase Half-life (t1/2) of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 14 | 13 |
Geometric Least Squares Mean (90% Confidence Interval) [Hours] |
11.344
|
12.415
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS Mean |
Estimated Value | 1.094 | |
Confidence Interval |
(2-Sided) 90% 0.959 to 1.249 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 14 | 13 |
Geometric Least Squares Mean (90% Confidence Interval) [Hours*micrograms per milliliter] |
20.3
|
23.4
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS Mean |
Estimated Value | 1.157 | |
Confidence Interval |
(2-Sided) 90% 1.059 to 1.265 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 1: AUC From Time 0 (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 14 | 13 |
Geometric Least Squares Mean (90% Confidence Interval) [Hours* micrograms per milliliter] |
20.6
|
23.9
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS Mean |
Estimated Value | 1.158 | |
Confidence Interval |
(2-Sided) 90% 1.062 to 1.264 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 2: Cmax of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 2:Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 14 |
Geometric Least Squares Mean (90% Confidence Interval) [Micrograms per milliliter] |
3.735
|
2.728
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS Mean |
Estimated Value | 0.730 | |
Confidence Interval |
(2-Sided) 90% 0.635 to 0.840 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 2: Lag Time Before Observation of Drug Concentrations (Tlag) of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 2:Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 14 |
Median (Full Range) [Hours] |
0.000
|
0.000
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
Estimated Value | 0.000 | |
Confidence Interval |
(2-Sided) 90% 0.000 to 0.000 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate. |
Title | Cohort 2: Tmax of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 2:Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 14 |
Median (Full Range) [Hours] |
2.500
|
2.000
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
Estimated Value | -0.467 | |
Confidence Interval |
(2-Sided) 90% -1.000 to 0.492 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate |
Title | Cohort 2: AUC(0-t) of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 2:Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 14 |
Geometric Least Squares Mean (90% Confidence Interval) [Hours*micrograms per milliliter] |
19.0
|
9.0
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS Mean |
Estimated Value | 0.476 | |
Confidence Interval |
(2-Sided) 90% 0.433 to 0.525 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 2: AUC(0-infinity) of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 2:Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 14 |
Geometric Least Squares Mean (90% Confidence Interval) [Hours*micrograms per milliliter] |
19.3
|
9.3
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS Mean |
Estimated Value | 0.478 | |
Confidence Interval |
(2-Sided) 90% 0.435 to 0.526 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 3: Cmax of Digoxin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Geometric Least Squares Mean (90% Confidence Interval) [Picograms per milliliter] |
1553.135
|
2381.259
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS mean |
Estimated Value | 1.533 | |
Confidence Interval |
(2-Sided) 90% 1.274 to 1.845 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 3: Tlag of Digoxin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Median (Full Range) [Hours] |
0.000
|
0.000
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
Estimated Value | 0.000 | |
Confidence Interval |
(2-Sided) 90% 0.000 to 0.000 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate. |
Title | Cohort 3: Tmax of Digoxin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Median (Full Range) [Hours] |
2.000
|
1.275
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
Estimated Value | -0.500 | |
Confidence Interval |
(2-Sided) 90% -1.000 to -0.233 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate. |
Title | Cohort 3: AUC(0-t) of Digoxin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population. Only those participants with data available at specified time points were analyzed. |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 17 |
Geometric Least Squares Mean (90% Confidence Interval) [Hours*picograms per milliliter] |
25353.1
|
30842.3
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS mean |
Estimated Value | 1.217 | |
Confidence Interval |
(2-Sided) 90% 1.085 to 1.363 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 3: AUC(0-infinity) of Digoxin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Geometric Least Squares Mean (90% Confidence Interval) [Hours*picograms per milliliter] |
30743.6
|
34456.5
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS mean |
Estimated Value | 1.121 | |
Confidence Interval |
(2-Sided) 90% 0.983 to 1.278 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 3: Cmax of Midazolam in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Geometric Least Squares Mean (90% Confidence Interval) [Nanograms per milliliter] |
5.238
|
6.507
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS mean |
Estimated Value | 1.242 | |
Confidence Interval |
(2-Sided) 90% 1.046 to 1.475 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 3: Tlag of Midazolam in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Median (Full Range) [Hours] |
0.000
|
0.000
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
Estimated Value | 0.000 | |
Confidence Interval |
(2-Sided) 90% 0.000 to 0.000 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate. |
Title | Cohort 3: Tmax of Midazolam in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Median (Full Range) [Hours] |
0.650
|
0.500
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
Estimated Value | 0.000 | |
Confidence Interval |
(2-Sided) 90% -0.250 to 0.800 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate. |
Title | Cohort 3: AUC(0-t) of Midazolam in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Geometric Least Squares Mean (90% Confidence Interval) [Hours*nanograms per milliliter] |
23.3
|
44.8
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS mean |
Estimated Value | 1.923 | |
Confidence Interval |
(2-Sided) 90% 1.622 to 2.278 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 3: AUC(0-infinity) of Midazolam in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Geometric Least Squares Mean (90% Confidence Interval) [Hours*nanograms per milliliter] |
24.9
|
47.4
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS mean |
Estimated Value | 1.902 | |
Confidence Interval |
(2-Sided) 90% 1.619 to 2.234 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted |
---|---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Micrograms per milliliter] |
5.436
(27.8)
|
5.143
(34.2)
|
Title | Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted |
---|---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 | 11 |
Median (Full Range) [Hours] |
2.000
|
1.500
|
Title | Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 24 Hours Post-dose (AUC[0-24]) of Gepotidacin Following Single Dose of 1500 mg in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted |
---|---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
20.9
(16.8)
|
19.0
(12.9)
|
Title | Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 48 Hours Post-dose (AUC[0-48]) of Gepotidacin Following Single Dose of 1500 mg in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted |
---|---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
21.9
(16.0)
|
20.0
(13.2)
|
Title | Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted |
---|---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
21.9
(16.0)
|
20.0
(13.2)
|
Title | Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted |
---|---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
22.3
(15.5)
|
20.4
(13.3)
|
Title | Cohort 4: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Micrograms per milliliter] |
11.204
(45.0)
|
Title | Cohort 4: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 11 |
Median (Full Range) [Hours] |
2.000
|
Title | Cohort 4: AUC From Time 0 (Predose) to Time Tau (AUC[0-tau]) of Gepotidacin in Plasma After the First Dose of 3000 Mg-Fed State |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
37.3
(25.4)
|
Title | Cohort 4: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Micrograms per milliliter] |
12.363
(21.3)
|
Title | Cohort 4: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 11 |
Median (Full Range) [Hours] |
2.000
|
Title | Cohort 4: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Evening Dose)-Fed State |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
46.7
(23.1)
|
Title | Cohort 4: Accumulation Ratio Based on Cmax (RoCmax) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Ratio] |
1.103
(39.3)
|
Title | Cohort 4: Accumulation Ratio Based on AUC(0-tau) (RoAUC) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) after the second dose, where 0 is the timepoint prior to second dose, divided by AUC(0-tau) after the first dose, where 0 is the predose timepoint prior to the first dose. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Ratio] |
1.254
(13.1)
|
Title | Cohort 4: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
84.6
(23.1)
|
Title | Cohort 4: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
90.8
(22.9)
|
Title | Cohort 4: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
91.4
(23.0)
|
Title | Cohort 4: Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE) |
---|---|
Description | An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment. |
Time Frame | Up to 22 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population comprised of all participants who took at least 1 dose of study intervention. |
Arm/Group Title | Cohort 4: Placebo | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|---|---|---|
Arm/Group Description | Japanese participants received a single oral dose of placebo matching gepotidacin under fed conditions in Period 1 or a single dose of placebo matching gepotidacin under fasted conditions in Period 2 or two doses of placebo (given 12 hours apart) matching gepotidacin under fed conditions in Period 3 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 3 | 11 | 11 | 11 |
Any SAE |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Any non-SAE |
0
0%
|
1
5.9%
|
2
20%
|
4
44.4%
|
Title | Cohort 4: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, Erythrocyte Mean Corpuscular Hemoglobin (MCH), Erythrocyte Mean Corpuscular Volume (MCV), Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose laboratory (lab) value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 (%). High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. |
Time Frame | Up to 22 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population |
Arm/Group Title | Cohort 4: Placebo | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|---|---|---|
Arm/Group Description | Japanese participants received a single oral dose of placebo matching gepotidacin under fed conditions in Period 1 or a single dose of placebo matching gepotidacin under fasted conditions in Period 2 or two doses of placebo (given 12 hours apart) matching gepotidacin under fed conditions in Period 3 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 3 | 11 | 11 | 11 |
Basophils; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Basophils; To Normal or No Change |
3
21.4%
|
11
64.7%
|
9
90%
|
10
111.1%
|
Basophils; To High |
0
0%
|
0
0%
|
2
20%
|
1
11.1%
|
Eosinophils; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Eosinophils; To Normal or No Change |
3
21.4%
|
10
58.8%
|
10
100%
|
10
111.1%
|
Eosinophils; To High |
0
0%
|
1
5.9%
|
1
10%
|
1
11.1%
|
MCH; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
MCH; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
MCH; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
MCV; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
MCV; To Normal or No Change |
2
14.3%
|
10
58.8%
|
10
100%
|
9
100%
|
MCV; To High |
1
7.1%
|
1
5.9%
|
1
10%
|
2
22.2%
|
Erythrocytes; To Low |
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
Erythrocytes; To Normal or No Change |
3
21.4%
|
10
58.8%
|
11
110%
|
10
111.1%
|
Erythrocytes; To High |
0
0%
|
1
5.9%
|
0
0%
|
0
0%
|
Hematocrit; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Hematocrit; To Normal or No Change |
3
21.4%
|
10
58.8%
|
11
110%
|
10
111.1%
|
Hematocrit; To High |
0
0%
|
1
5.9%
|
0
0%
|
1
11.1%
|
Hemoglobin; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Hemoglobin; To Normal or No Change |
3
21.4%
|
10
58.8%
|
11
110%
|
11
122.2%
|
Hemoglobin; To High |
0
0%
|
1
5.9%
|
0
0%
|
0
0%
|
Leukocytes; To Low |
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
Leukocytes; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
10
111.1%
|
Leukocytes; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Lymphocytes; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Lymphocytes; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Lymphocytes; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Monocytes; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Monocytes; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Monocytes; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Neutrophils; To Low |
0
0%
|
0
0%
|
1
10%
|
1
11.1%
|
Neutrophils; To Normal or No Change |
3
21.4%
|
11
64.7%
|
10
100%
|
10
111.1%
|
Neutrophils; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Platelets; To Low |
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
Platelets; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
10
111.1%
|
Platelets; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Title | Cohort 4: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including Alanine Aminotransferase (ALT), Albumin, Alkaline Phosphatase (Alk Phos), Aspartate Aminotransferase (AST), Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, Blood Urea Nitrogen (BUN). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. |
Time Frame | Up to 22 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population |
Arm/Group Title | Cohort 4: Placebo | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|---|---|---|
Arm/Group Description | Japanese participants received a single oral dose of placebo matching gepotidacin under fed conditions in Period 1 or a single dose of placebo matching gepotidacin under fasted conditions in Period 2 or two doses of placebo (given 12 hours apart) matching gepotidacin under fed conditions in Period 3 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 3 | 11 | 11 | 11 |
ALT; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
ALT; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
ALT; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Albumin; To Low |
1
7.1%
|
0
0%
|
0
0%
|
0
0%
|
Albumin; To Normal or No Change |
2
14.3%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Albumin; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Alk Phos; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Alk Phos; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Alk Phos; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
AST; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
AST; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
AST; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Bilirubin; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Bilirubin; To Normal or No Change |
2
14.3%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Bilirubin; To High |
1
7.1%
|
0
0%
|
0
0%
|
0
0%
|
Calcium; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Calcium; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Calcium; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Carbon Dioxide; To Low |
0
0%
|
0
0%
|
1
10%
|
0
0%
|
Carbon Dioxide; To Normal or No Change |
3
21.4%
|
11
64.7%
|
10
100%
|
11
122.2%
|
Carbon Dioxide; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Chloride; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Chloride; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Chloride; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Creatine Kinase; To Low |
1
7.1%
|
0
0%
|
0
0%
|
1
11.1%
|
Creatine Kinase; To Normal or No Change |
2
14.3%
|
11
64.7%
|
11
110%
|
9
100%
|
Creatine Kinase; To High |
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
Creatinine; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Creatinine; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Creatinine;To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Direct Bilirubin; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Direct Bilirubin; To Normal or No Change |
2
14.3%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Direct Bilirubin; To High |
1
7.1%
|
0
0%
|
0
0%
|
0
0%
|
Glucose; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Glucose; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Glucose; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Magnesium; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Magnesium; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Magnesium; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Potassium; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Potassium; To Normal or No Change |
2
14.3%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Potassium; To High |
1
7.1%
|
0
0%
|
0
0%
|
0
0%
|
Protein; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Protein; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Protein; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Sodium; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Sodium; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Sodium; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
BUN; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
BUN; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
BUN; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Title | Cohort 4: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | Urine samples were collected at indicated time points for the analysis of urinalysis parameters including potential of hydrogen (pH) of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. |
Time Frame | Up to 22 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population |
Arm/Group Title | Cohort 4: Placebo | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|---|---|---|
Arm/Group Description | Japanese participants received a single oral dose of placebo matching gepotidacin under fed conditions in Period 1 or a single dose of placebo matching gepotidacin under fasted conditions in Period 2 or two doses of placebo (given 12 hours apart) matching gepotidacin under fed conditions in Period 3 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 3 | 11 | 11 | 11 |
Bilirubin; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Bilirubin; To Abnormal |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Glucose; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Glucose; To Abnormal |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Ketones; To Normal or No Change |
2
14.3%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Ketones; To Abnormal |
1
7.1%
|
0
0%
|
0
0%
|
0
0%
|
Leukocyte Esterase; To Normal or No Change |
2
14.3%
|
9
52.9%
|
11
110%
|
9
100%
|
Leukocyte Esterase; To Abnormal |
1
7.1%
|
2
11.8%
|
0
0%
|
2
22.2%
|
Nitrite; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
10
111.1%
|
Nitrite; To Abnormal |
0
0%
|
0
0%
|
0
0%
|
1
11.1%
|
Occult Blood; To Normal or No Change |
2
14.3%
|
11
64.7%
|
10
100%
|
10
111.1%
|
Occult Blood; To Abnormal |
1
7.1%
|
0
0%
|
1
10%
|
1
11.1%
|
Protein; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Protein; To Abnormal |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
pH; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
pH; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
pH; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Specific Gravity; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Specific Gravity; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Specific Gravity; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Title | Cohort 4: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. |
Time Frame | Up to 22 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population |
Arm/Group Title | Cohort 4: Placebo | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|---|---|---|
Arm/Group Description | Japanese participants received a single oral dose of placebo matching gepotidacin under fed conditions in Period 1 or a single dose of placebo matching gepotidacin under fasted conditions in Period 2 or two doses of placebo (given 12 hours apart) matching gepotidacin under fed conditions in Period 3 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 3 | 11 | 11 | 11 |
DBP; To Low |
0
0%
|
1
5.9%
|
0
0%
|
0
0%
|
DBP; To Normal or No Change |
3
21.4%
|
10
58.8%
|
11
110%
|
11
122.2%
|
DBP; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
SBP; To Low |
0
0%
|
1
5.9%
|
1
10%
|
0
0%
|
SBP; To Normal or No Change |
3
21.4%
|
10
58.8%
|
10
100%
|
11
122.2%
|
SBP; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Pulse rate; To Low |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Pulse rate; To Normal or No Change |
3
21.4%
|
11
64.7%
|
11
110%
|
11
122.2%
|
Pulse rate; To High |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Title | Cohort 4: Number of Participants With Any Increase in Maximum Post-Baseline Electrocardiogram (ECG) Parameter Corrected QT (QTc) Interval |
---|---|
Description | A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the Bazett formula (QTcB) Interval and corrected QT interval using the Fridericia formula (QTcF) Interval has been reported. |
Time Frame | Up to 22 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population |
Arm/Group Title | Cohort 4: Placebo | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|---|---|---|
Arm/Group Description | Japanese participants received a single oral dose of placebo matching gepotidacin under fed conditions in Period 1 or a single dose of placebo matching gepotidacin under fasted conditions in Period 2 or two doses of placebo (given 12 hours apart) matching gepotidacin under fed conditions in Period 3 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 3 | 11 | 11 | 11 |
QTcB Interval |
1
7.1%
|
8
47.1%
|
3
30%
|
9
100%
|
QTcF Interval |
1
7.1%
|
1
5.9%
|
0
0%
|
2
22.2%
|
Title | Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted |
---|---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 | 11 |
Geometric Least Squares Mean (90% Confidence Interval) [Micrograms per milliliter] |
5.421
|
5.158
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of geometric LS mean |
Estimated Value | 1.051 | |
Confidence Interval |
(2-Sided) 90% 0.824 to 1.340 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 4: Tlag of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted |
---|---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 | 11 |
Median (Full Range) [Hours] |
0.000
|
0.000
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
Estimated Value | 0.000 | |
Confidence Interval |
(2-Sided) 90% 0.000 to 0.250 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate. |
Title | Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted |
---|---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 | 11 |
Median (Full Range) [Hours] |
2.000
|
1.500
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
Estimated Value | 0.500 | |
Confidence Interval |
(2-Sided) 90% -0.500 to 1.250 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate. |
Title | Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted |
---|---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 | 11 |
Geometric Least Squares Mean (90% Confidence Interval) [Hours*Micrograms per milliliter] |
21.9
|
20.0
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of geometric LS mean |
Estimated Value | 1.094 | |
Confidence Interval |
(2-Sided) 90% 0.987 to 1.212 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted |
---|---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 | 11 |
Geometric Least Squares Mean (90% Confidence Interval) [Hours*Micrograms per milliliter] |
22.3
|
20.4
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of geometric LS mean |
Estimated Value | 1.095 | |
Confidence Interval |
(2-Sided) 90% 0.991 to 1.209 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 1: AUC (0-24) of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 14 | 13 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
19.3
(32.6)
|
21.9
(29.7)
|
Title | Cohort 1: AUC(0-48) of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 14 | 13 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
20.3
(31.4)
|
23.0
(28.4)
|
Title | Cohort 1: Tlag of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 14 | 13 |
Median (Full Range) [Hours] |
0.000
|
0.000
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Median Difference (Final Values) |
Estimated Value | 0.000 | |
Confidence Interval |
(2-Sided) 90% -0.250 to 0.000 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | The median difference and the 90% CI of the median difference were from Hodges-Lehmann estimate. |
Title | Cohort 1: Apparent Volume of Distribution (Vz/F) of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 14 | 13 |
Geometric Mean (Geometric Coefficient of Variation) [Liters] |
1190.16
(34.0)
|
1143.29
(30.6)
|
Title | Cohort 1: Apparent Oral Clearance (CL/F) of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours Post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 14 | 13 |
Geometric Mean (Geometric Coefficient of Variation) [Liters per Hour] |
72.72
(31.2)
|
64.14
(28.0)
|
Title | Cohort 1: Total Unchanged Drug (Ae Total) of Gepotidacin in Urine |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population. Only those participants with data available at specified time points were analyzed. |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 12 | 13 |
Geometric Least Squares Mean (90% Confidence Interval) [Milligrams] |
337.92
|
410.10
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of geometric LS mean |
Estimated Value | 1.214 | |
Confidence Interval |
(2-Sided) 90% 1.000 to 1.473 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 1: AUC(0-24) of Gepotidacin in Urine |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours Post-dose in each Treatment periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 14 | 13 |
Geometric Least Squares Mean (90% Confidence Interval) [Hours*micrograms per milliliter] |
3292.1
|
3612.4
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of geometric LS mean |
Estimated Value | 1.097 | |
Confidence Interval |
(2-Sided) 90% 0.948 to 1.270 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 1: AUC(0-48) of Gepotidacin in Urine |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 14 | 13 |
Geometric Least Squares Mean (90% Confidence Interval) [Hours*micrograms per milliliter] |
3578.2
|
3831.1
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of geometric LS mean |
Estimated Value | 1.071 | |
Confidence Interval |
(2-Sided) 90% 0.939 to 1.221 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 1: Renal Clearance (CLr) of Gepotidacin |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90% CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population. Only those participants with data available at specified time points were analyzed. |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 12 | 13 |
Geometric Least Squares Mean (90% Confidence Interval) [Liters per Hour] |
16.06
|
17.59
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of geometric LS mean |
Estimated Value | 1.096 | |
Confidence Interval |
(2-Sided) 90% 0.930 to 1.292 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 1: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals. |
Time Frame | 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles). |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 14 | 13 |
Ae (0-2), n=14, 13 |
28.66
(185.9)
|
NA
(NA)
|
Ae (2-4), n=14, 12 |
89.18
(120.8)
|
142.99
(42.7)
|
Ae (4-6), n=14, 13 |
50.52
(119.1)
|
82.77
(44.0)
|
Ae (6-8); n=14, 13 |
34.38
(56.2)
|
46.22
(55.3)
|
Ae (8-12), n=12, 13 |
29.90
(38.3)
|
30.97
(38.0)
|
Ae (12-24), n=14, 13 |
25.44
(38.1)
|
22.04
(121.3)
|
Ae (24-36), n=14, 13 |
10.88
(43.1)
|
8.76
(89.6)
|
Ae (36-48), n=14, 13 |
4.50
(39.3)
|
4.08
(88.5)
|
Title | Cohort 1: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 percent (%). |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours Post-dose in each Treatment periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population. Only those participants with data available at specified time points were analyzed. |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 12 | 13 |
Geometric Mean (Geometric Coefficient of Variation) [Percent dose excreted] |
22.72
(53.2)
|
26.90
(21.3)
|
Title | Cohort 1: Number of Participants With SAE and Non-SAE |
---|---|
Description | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment. |
Time Frame | Up to 17 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 14 | 13 |
Any SAE |
0
0%
|
0
0%
|
Any non-SAE |
0
0%
|
0
0%
|
Title | Cohort 1: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100 %. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. |
Time Frame | Up to 17 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 14 | 13 |
Basophils; To Low |
0
0%
|
0
0%
|
Basophils; To Normal or No Change |
14
100%
|
11
64.7%
|
Basophils; To High |
0
0%
|
2
11.8%
|
Eosinophils; To Low |
0
0%
|
0
0%
|
Eosinophils; To Normal or No Change |
14
100%
|
13
76.5%
|
Eosinophils; To High |
0
0%
|
0
0%
|
MCH; To Low |
0
0%
|
0
0%
|
MCH; To Normal or No Change |
14
100%
|
13
76.5%
|
MCH; To High |
0
0%
|
0
0%
|
MCV; To Low |
0
0%
|
0
0%
|
MCV; To Normal or No Change |
13
92.9%
|
13
76.5%
|
MCV; To High |
1
7.1%
|
0
0%
|
Erythrocytes; To Low |
0
0%
|
2
11.8%
|
Erythrocytes; To Normal or No Change |
14
100%
|
11
64.7%
|
Erythrocytes; To High |
0
0%
|
0
0%
|
Hematocrit; To Low |
0
0%
|
1
5.9%
|
Hematocrit; To Normal or No Change |
13
92.9%
|
12
70.6%
|
Hematocrit; To High |
1
7.1%
|
0
0%
|
Hemoglobin; To Low |
0
0%
|
0
0%
|
Hemoglobin; To Normal or No Change |
14
100%
|
13
76.5%
|
Hemoglobin; To High |
0
0%
|
0
0%
|
Leukocytes; To Low |
0
0%
|
0
0%
|
Leukocytes; To Normal or No Change |
13
92.9%
|
13
76.5%
|
Leukocytes; To High |
1
7.1%
|
0
0%
|
Lymphocytes; To Low |
0
0%
|
0
0%
|
Lymphocytes; To Normal or No Change |
14
100%
|
12
70.6%
|
Lymphocytes; To High |
0
0%
|
1
5.9%
|
Monocytes; To Low |
0
0%
|
0
0%
|
Monocytes; To Normal or No Change |
13
92.9%
|
13
76.5%
|
Monocytes; To High |
1
7.1%
|
0
0%
|
Neutrophils; To Low |
0
0%
|
1
5.9%
|
Neutrophils; To Normal or No Change |
13
92.9%
|
12
70.6%
|
Neutrophils; To High |
1
7.1%
|
0
0%
|
Platelets; To Low |
0
0%
|
0
0%
|
Platelets; To Normal or No Change |
14
100%
|
13
76.5%
|
Platelets; To High |
0
0%
|
0
0%
|
Title | Cohort 1: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. |
Time Frame | Up to 17 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 14 | 13 |
ALT; To Low |
0
0%
|
0
0%
|
ALT; To Normal or No Change |
14
100%
|
11
64.7%
|
ALT; To High |
0
0%
|
2
11.8%
|
Albumin; To Low |
0
0%
|
1
5.9%
|
Albumin; To Normal or No Change |
14
100%
|
12
70.6%
|
Albumin; To High |
0
0%
|
0
0%
|
Alk Phos; To Low |
0
0%
|
0
0%
|
Alk Phos; To Normal or No Change |
14
100%
|
13
76.5%
|
Alk Phos; To High |
0
0%
|
0
0%
|
AST; To Low |
0
0%
|
0
0%
|
AST; To Normal or No Change |
14
100%
|
12
70.6%
|
AST; To High |
0
0%
|
1
5.9%
|
Bilirubin; To Low |
0
0%
|
1
5.9%
|
Bilirubin; To Normal or No Change |
14
100%
|
12
70.6%
|
Bilirubin; To High |
0
0%
|
0
0%
|
Calcium; To Low |
0
0%
|
0
0%
|
Calcium; To Normal or No Change |
14
100%
|
13
76.5%
|
Calcium; To High |
0
0%
|
0
0%
|
Carbon Dioxide; To Low |
1
7.1%
|
0
0%
|
Carbon Dioxide; To Normal or No Change |
13
92.9%
|
13
76.5%
|
Carbon Dioxide; To High |
0
0%
|
0
0%
|
Chloride; To Low |
0
0%
|
0
0%
|
Chloride; To Normal or No Change |
14
100%
|
12
70.6%
|
Chloride; To High |
0
0%
|
1
5.9%
|
Creatine Kinase; To Low |
1
7.1%
|
0
0%
|
Creatine Kinase; To Normal or No Change |
13
92.9%
|
13
76.5%
|
Creatine Kinase; To High |
0
0%
|
0
0%
|
Creatinine; To Low |
0
0%
|
0
0%
|
Creatinine; To Normal or No Change |
14
100%
|
10
58.8%
|
Creatinine; To High |
0
0%
|
3
17.6%
|
Direct Bilirubin; To Low |
0
0%
|
0
0%
|
Direct Bilirubin; To Normal or No Change |
14
100%
|
13
76.5%
|
Direct Bilirubin; To High |
0
0%
|
0
0%
|
Glucose; To Low |
0
0%
|
0
0%
|
Glucose; To Normal or No Change |
14
100%
|
13
76.5%
|
Glucose; To High |
0
0%
|
0
0%
|
Magnesium; To Low |
0
0%
|
0
0%
|
Magnesium; To Normal or No Change |
14
100%
|
13
76.5%
|
Magnesium; To High |
0
0%
|
0
0%
|
Potassium; To Low |
0
0%
|
0
0%
|
Potassium; To Normal or No Change |
14
100%
|
12
70.6%
|
Potassium; To High |
0
0%
|
1
5.9%
|
Protein; To Low |
0
0%
|
0
0%
|
Protein; To Normal or No Change |
14
100%
|
13
76.5%
|
Protein; To High |
0
0%
|
0
0%
|
Sodium; To Low |
0
0%
|
0
0%
|
Sodium; To Normal or No Change |
14
100%
|
13
76.5%
|
Sodium; To High |
0
0%
|
0
0%
|
BUN; To Low |
0
0%
|
0
0%
|
BUN; To Normal or No Change |
14
100%
|
13
76.5%
|
BUN; To High |
0
0%
|
0
0%
|
Title | Cohort 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. |
Time Frame | Up to 17 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 14 | 13 |
Bilirubin; To Normal or No Change |
14
100%
|
13
76.5%
|
Bilirubin; To Abnormal |
0
0%
|
0
0%
|
Glucose; To Normal or No Change |
14
100%
|
13
76.5%
|
Glucose; To Abnormal |
0
0%
|
0
0%
|
Ketones; To Normal or No Change |
14
100%
|
13
76.5%
|
Ketones; To Abnormal |
0
0%
|
0
0%
|
Leukocyte Esterase; To Normal or No Change |
12
85.7%
|
13
76.5%
|
Leukocyte Esterase; To Abnormal |
2
14.3%
|
0
0%
|
Nitrite; To Normal or No Change |
14
100%
|
13
76.5%
|
Nitrite; To Abnormal |
0
0%
|
0
0%
|
Occult Blood; To Normal or No Change |
13
92.9%
|
11
64.7%
|
Occult Blood; To Abnormal |
1
7.1%
|
2
11.8%
|
Protein; To Normal or No Change |
14
100%
|
13
76.5%
|
Protein; To Abnormal |
0
0%
|
0
0%
|
pH; To Low |
0
0%
|
0
0%
|
pH; To Normal or No Change |
14
100%
|
13
76.5%
|
pH; To High |
0
0%
|
0
0%
|
Specific Gravity; To Low |
0
0%
|
0
0%
|
Specific Gravity; To Normal or No Change |
13
92.9%
|
13
76.5%
|
Specific Gravity; To High |
1
7.1%
|
0
0%
|
Title | Cohort 1: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. |
Time Frame | Up to 17 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 14 | 13 |
DBP; To Low |
0
0%
|
0
0%
|
DBP; To Normal or No Change |
14
100%
|
13
76.5%
|
DBP; To High |
0
0%
|
0
0%
|
SBP; To Low |
0
0%
|
0
0%
|
SBP; To Normal or No Change |
14
100%
|
13
76.5%
|
SBP; To High |
0
0%
|
0
0%
|
Pulse rate; To Low |
0
0%
|
0
0%
|
Pulse rate; To Normal or No Change |
14
100%
|
13
76.5%
|
Pulse rate; To High |
0
0%
|
0
0%
|
Title | Cohort 1: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval |
---|---|
Description | A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported. |
Time Frame | Up to 17 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population |
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. |
Measure Participants | 14 | 13 |
QTcB Interval |
3
21.4%
|
4
23.5%
|
QTcF Interval |
0
0%
|
1
5.9%
|
Title | Cohort 2: AUC(0-24) of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 2:Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 14 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
17.9
(28.6)
|
8.9
(29.6)
|
Title | Cohort 2: AUC(0-48) of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 2:Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 14 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
19.0
(27.7)
|
9.5
(28.5)
|
Title | Cohort 2: T1/2 of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 2:Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 14 |
Geometric Mean (Geometric Coefficient of Variation) [Hours] |
10.882
(25.5)
|
10.972
(17.2)
|
Title | Cohort 2: Vz/F of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 2:Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 14 |
Geometric Mean (Geometric Coefficient of Variation) [Liters] |
1217.45
(37.0)
|
2460.46
(39.2)
|
Title | Cohort 2: CL/F of Gepotidacin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 2:Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 14 |
Geometric Mean (Geometric Coefficient of Variation) [Liters per Hour] |
77.55
(27.6)
|
155.43
(27.9)
|
Title | Cohort 2: Ae Total of Gepotidacin in Urine |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 2:Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 14 |
Geometric Least Squares Mean (90% Confidence Interval) [Milligrams] |
312.73
|
156.05
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of geometric LS mean |
Estimated Value | 0.499 | |
Confidence Interval |
(2-Sided) 90% 0.441 to 0.565 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 2: AUC(0-24) of Gepotidacin in Urine |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 2:Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 14 |
Geometric Least Squares Mean (90% Confidence Interval) [Hours*micrograms per milliliter] |
3081.3
|
1352.4
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of geometric LS mean |
Estimated Value | 0.439 | |
Confidence Interval |
(2-Sided) 90% 0.370 to 0.521 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 2: AUC(0-48) of Gepotidacin in Urine |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 2:Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 14 |
Geometric Least Squares Mean (90% Confidence Interval) [Hours*micrograms per milliliter] |
3370.1
|
1476.8
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of geometric LS mean |
Estimated Value | 0.438 | |
Confidence Interval |
(2-Sided) 90% 0.372 to 0.516 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 2: CLr of Gepotidacin |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 2:Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 14 |
Geometric Least Squares Mean (90% Confidence Interval) [Liters per Hour] |
16.49
|
17.07
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of geometric LS mean |
Estimated Value | 1.036 | |
Confidence Interval |
(2-Sided) 90% 0.950 to 1.129 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 2: Ae(t1-t2) of Gepotidacin |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals. |
Time Frame | 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 2:Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 14 |
Ae (0-2) |
12.67
(567.5)
|
NA
(NA)
|
Ae (2-4) |
79.84
(65.6)
|
55.81
(47.4)
|
Ae (4-6) |
67.48
(44.3)
|
21.66
(66.4)
|
Ae (6-8) |
33.92
(50.5)
|
13.82
(56.1)
|
Ae (8-12) |
27.59
(63.1)
|
9.19
(50.7)
|
Ae (12-24) |
21.17
(79.2)
|
11.51
(36.4)
|
Ae (24-36) |
11.04
(77.9)
|
4.74
(42.7)
|
Ae (36-48) |
3.61
(90.3)
|
2.75
(31.8)
|
Title | Cohort 2: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 2:Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 14 |
Geometric Mean (Geometric Coefficient of Variation) [Percent dose excreted] |
20.85
(16.9)
|
10.42
(25.4)
|
Title | Cohort 2: Number of Participants With SAE and Non-SAE |
---|---|
Description | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment. |
Time Frame | Up to 26 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Participants with adverse events that occurred during Days 1 to 7 in Period 2 after the exposure of rifampicin 600 mg and those occurred during Days 8 to 9 in Period 2 after exposure of gepotidacin 1500 mg + Rifampicin 600 mg were summarized separately. Only those participants with data available at specified time points were analyzed. |
Arm/Group Title | Cohort 2: Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2 (Days 1 to 7) Rifampicin 600 mg | Cohort 2: Period 2 (Days 8 to 9) Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) of Period 2 in Cohort 2. | Participants received a single dose of gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 17 | 14 |
Any SAE |
0
0%
|
0
0%
|
0
0%
|
Any non-SAE |
3
21.4%
|
2
11.8%
|
2
20%
|
Title | Cohort 2: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. |
Time Frame | Up to 26 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population |
Arm/Group Title | Cohort 2: Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 17 |
Basophils; To Low |
0
0%
|
0
0%
|
Basophils; To Normal or No Change |
17
121.4%
|
16
94.1%
|
Basophils; To High |
0
0%
|
1
5.9%
|
Eosinophils; To Low |
0
0%
|
0
0%
|
Eosinophils; To Normal or No Change |
15
107.1%
|
14
82.4%
|
Eosinophils; To High |
2
14.3%
|
3
17.6%
|
MCH; To Low |
0
0%
|
0
0%
|
MCH; To Normal or No Change |
17
121.4%
|
17
100%
|
MCH; To High |
0
0%
|
0
0%
|
MCV; To Low |
0
0%
|
0
0%
|
MCV; To Normal or No Change |
17
121.4%
|
17
100%
|
MCV; To High |
0
0%
|
0
0%
|
Erythrocytes; To Low |
0
0%
|
0
0%
|
Erythrocytes; To Normal or No Change |
17
121.4%
|
17
100%
|
Erythrocytes; To High |
0
0%
|
0
0%
|
Hematocrit; To Low |
0
0%
|
0
0%
|
Hematocrit; To Normal or No Change |
14
100%
|
15
88.2%
|
Hematocrit; To High |
3
21.4%
|
2
11.8%
|
Hemoglobin; To Low |
0
0%
|
0
0%
|
Hemoglobin; To Normal or No Change |
17
121.4%
|
17
100%
|
Hemoglobin; To High |
0
0%
|
0
0%
|
Leukocytes; To Low |
0
0%
|
1
5.9%
|
Leukocytes; To Normal or No Change |
17
121.4%
|
16
94.1%
|
Leukocytes; To High |
0
0%
|
0
0%
|
Lymphocytes; To Low |
0
0%
|
0
0%
|
Lymphocytes; To Normal or No Change |
17
121.4%
|
15
88.2%
|
Lymphocytes; To High |
0
0%
|
2
11.8%
|
Monocytes; To Low |
1
7.1%
|
3
17.6%
|
Monocytes; To Normal or No Change |
15
107.1%
|
14
82.4%
|
Monocytes; To High |
1
7.1%
|
0
0%
|
Neutrophils; To Low |
0
0%
|
4
23.5%
|
Neutrophils; To Normal or No Change |
17
121.4%
|
13
76.5%
|
Neutrophils; To High |
0
0%
|
0
0%
|
Platelets; To Low |
0
0%
|
0
0%
|
Platelets; To Normal or No Change |
17
121.4%
|
16
94.1%
|
Platelets; To High |
0
0%
|
1
5.9%
|
Title | Cohort 2: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. |
Time Frame | Up to 26 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population |
Arm/Group Title | Cohort 2: Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 17 |
ALT; To Low |
0
0%
|
0
0%
|
ALT; To Normal or No Change |
17
121.4%
|
15
88.2%
|
ALT; To High |
0
0%
|
2
11.8%
|
Albumin; To Low |
0
0%
|
0
0%
|
Albumin; To Normal or No Change |
17
121.4%
|
17
100%
|
Albumin; To High |
0
0%
|
0
0%
|
Alk Phos; To Low |
0
0%
|
0
0%
|
Alk Phos; To Normal or No Change |
17
121.4%
|
17
100%
|
Alk Phos; To High |
0
0%
|
0
0%
|
AST; To Low |
0
0%
|
0
0%
|
AST; To Normal or No Change |
17
121.4%
|
16
94.1%
|
AST; To High |
0
0%
|
1
5.9%
|
Bilirubin; To Low |
0
0%
|
2
11.8%
|
Bilirubin; To Normal or No Change |
17
121.4%
|
15
88.2%
|
Bilirubin; To High |
0
0%
|
0
0%
|
Calcium; To Low |
0
0%
|
0
0%
|
Calcium; To Normal or No Change |
17
121.4%
|
17
100%
|
Calcium; To High |
0
0%
|
0
0%
|
Carbon Dioxide; To Low |
0
0%
|
3
17.6%
|
Carbon Dioxide; To Normal or No Change |
17
121.4%
|
14
82.4%
|
Carbon Dioxide; To High |
0
0%
|
0
0%
|
Chloride; To Low |
0
0%
|
0
0%
|
Chloride; To Normal or No Change |
17
121.4%
|
17
100%
|
Chloride; To High |
0
0%
|
0
0%
|
Creatine Kinase; To Low |
0
0%
|
0
0%
|
Creatine Kinase; To Normal or No Change |
17
121.4%
|
17
100%
|
Creatine Kinase; To High |
0
0%
|
0
0%
|
Creatinine; To Low |
0
0%
|
0
0%
|
Creatinine; To Normal or No Change |
16
114.3%
|
16
94.1%
|
Creatinine; To High |
1
7.1%
|
1
5.9%
|
Direct Bilirubin; To Low |
0
0%
|
0
0%
|
Direct Bilirubin; To Normal or No Change |
17
121.4%
|
17
100%
|
Direct Bilirubin; To High |
0
0%
|
0
0%
|
Glucose; To Low |
0
0%
|
0
0%
|
Glucose; To Normal or No Change |
17
121.4%
|
16
94.1%
|
Glucose; To High |
0
0%
|
1
5.9%
|
Magnesium; To Low |
0
0%
|
0
0%
|
Magnesium; To Normal or No Change |
17
121.4%
|
17
100%
|
Magnesium; To High |
0
0%
|
0
0%
|
Potassium; To Low |
0
0%
|
0
0%
|
Potassium; To Normal or No Change |
16
114.3%
|
15
88.2%
|
Potassium; To High |
1
7.1%
|
2
11.8%
|
Protein; To Low |
0
0%
|
0
0%
|
Protein; To Normal or No Change |
17
121.4%
|
17
100%
|
Protein; To High |
0
0%
|
0
0%
|
Sodium; To Low |
0
0%
|
0
0%
|
Sodium; To Normal or No Change |
17
121.4%
|
17
100%
|
Sodium; To High |
0
0%
|
0
0%
|
BUN; To Low |
0
0%
|
0
0%
|
BUN; To Normal or No Change |
17
121.4%
|
17
100%
|
BUN; To High |
0
0%
|
0
0%
|
Title | Cohort 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. |
Time Frame | Up to 26 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Only those participants with data available at specified time points were analyzed. |
Arm/Group Title | Cohort 2: Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 16 |
Bilirubin; To Normal or No Change |
17
121.4%
|
16
94.1%
|
Bilirubin; To Abnormal |
0
0%
|
0
0%
|
Glucose; To Normal or No Change |
17
121.4%
|
16
94.1%
|
Glucose; To Abnormal |
0
0%
|
0
0%
|
Ketones; To Normal or No Change |
17
121.4%
|
16
94.1%
|
Ketones; To Abnormal |
0
0%
|
0
0%
|
Leukocyte Esterase; To Normal or No Change |
16
114.3%
|
14
82.4%
|
Leukocyte Esterase; To Abnormal |
1
7.1%
|
2
11.8%
|
Nitrite; To Normal or No Change |
17
121.4%
|
15
88.2%
|
Nitrite; To Abnormal |
0
0%
|
1
5.9%
|
Occult Blood; To Normal or No Change |
17
121.4%
|
14
82.4%
|
Occult Blood; To Abnormal |
0
0%
|
2
11.8%
|
Protein; To Normal or No Change |
17
121.4%
|
16
94.1%
|
Protein; To Abnormal |
0
0%
|
0
0%
|
pH; To Low |
0
0%
|
0
0%
|
pH; To Normal or No Change |
17
121.4%
|
16
94.1%
|
pH; To High |
0
0%
|
0
0%
|
Specific Gravity; To Low |
0
0%
|
0
0%
|
Specific Gravity; To Normal or No Change |
14
100%
|
15
88.2%
|
Specific Gravity; To High |
3
21.4%
|
1
5.9%
|
Title | Cohort 2: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. |
Time Frame | Up to 26 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Only those participants with data available at specified time points were analyzed. |
Arm/Group Title | Cohort 2: Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 14 |
DBP; To Low |
0
0%
|
0
0%
|
DBP; To Normal or No Change |
16
114.3%
|
14
82.4%
|
DBP; To High |
1
7.1%
|
0
0%
|
SBP; To Low |
0
0%
|
0
0%
|
SBP; To Normal or No Change |
17
121.4%
|
14
82.4%
|
SBP; To High |
0
0%
|
0
0%
|
Pulse rate; To Low |
0
0%
|
0
0%
|
Pulse rate; To Normal or No Change |
17
121.4%
|
14
82.4%
|
Pulse rate; To High |
0
0%
|
0
0%
|
Title | Cohort 2: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval |
---|---|
Description | A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported. |
Time Frame | Up to 26 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population. Only those participants with data available at specified time points were analyzed. |
Arm/Group Title | Cohort 2: Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2: Gepotidacin 1500 mg + Rifampicin 600 mg |
---|---|---|
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) followed by a single dose of Gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. |
Measure Participants | 17 | 14 |
QTcB Interval |
2
14.3%
|
2
11.8%
|
QTcF Interval |
0
0%
|
1
5.9%
|
Title | Cohort 3: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose) |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 18 |
Geometric Mean (Geometric Coefficient of Variation) [Micrograms per milliliter] |
7.867
(36.8)
|
Title | Cohort 3: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose) |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 18 |
Median (Full Range) [Hours] |
2.500
|
Title | Cohort 3: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose) |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 18 |
Median (Full Range) [Hours] |
0.250
|
Title | Cohort 3: AUC(0-tau) of Gepotidacin in Plasma First Dose of 3000 mg (First Dose) |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 18 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
29.8
(30.8)
|
Title | Cohort 3: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose) |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 18 |
Geometric Mean (Geometric Coefficient of Variation) [Micrograms per milliliter] |
10.051
(47.7)
|
Title | Cohort 3: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose) |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 18 |
Median (Full Range) [Hours] |
2.000
|
Title | Cohort 3: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose) |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 18 |
Geometric Mean (Geometric Coefficient of Variation) [Hours* micrograms per milliliter] |
41.9
(30.2)
|
Title | Cohort 3: RoCmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose) |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 18 |
Geometric Mean (Geometric Coefficient of Variation) [Ratio] |
1.278
(54.4)
|
Title | Cohort 3: RoAUC of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose) |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Accumulation ratio was calculated as AUC(0-tau) after the second dose, where 0 is the timepoint prior to second dose, divided by AUC(0-tau) after the first dose, where 0 is the predose timepoint prior to the first dose. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 18 |
Geometric Mean (Geometric Coefficient of Variation) [Ratio] |
1.406
(27.5)
|
Title | Cohort 3: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose) |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 18 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
73.2
(26.8)
|
Title | Cohort 3: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose) |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 18 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
81.2
(25.9)
|
Title | Cohort 3: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose) |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population. Only those participants with data available at specified time points were analyzed. |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 17 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
85.2
(20.1)
|
Title | Cohort 3: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose) |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population. Only those participants with data available at specified time points were analyzed. |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 17 |
Geometric Mean (Geometric Coefficient of Variation) [Liters] |
959.42
(30.0)
|
Title | Cohort 3: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose) |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population. Only those participants with data available at specified time points were analyzed. |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 17 |
Geometric Mean (Geometric Coefficient of Variation) [Liters per Hour] |
69.99
(20.1)
|
Title | Cohort 3: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose+ Second Dose) |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 Hours, 14 Hours, 14 Hours 30 Hours, 15, 16,18,20,24,36, 48, 60 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population. Only those participants with data available at specified time points were analyzed. |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 17 |
Geometric Mean (Geometric Coefficient of Variation) [Hours] |
9.501
(22.5)
|
Title | Cohort 3: Minimum Observed Concentration (Cmin) of Digoxin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Geometric Least Squares Mean (90% Confidence Interval) [Picograms per milliliter] |
44.127
|
77.447
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS mean |
Estimated Value | 1.755 | |
Confidence Interval |
(2-Sided) 90% 1.304 to 2.363 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 3: T1/2 of Digoxin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Geometric Least Squares Mean (90% Confidence Interval) [Hours] |
39.367
|
32.777
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS mean |
Estimated Value | 0.833 | |
Confidence Interval |
(2-Sided) 90% 0.769 to 0.902 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 3: Vz/F of Digoxin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Geometric Least Squares Mean (90% Confidence Interval) [Liters] |
923.75
|
688.49
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS mean |
Estimated Value | 0.745 | |
Confidence Interval |
(2-Sided) 90% 0.653 to 0.850 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 3: CL/F of Digoxin in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of digoxin was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 24 Hours, 36 Hours, 48 Hours, 72 Hours, 96 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Geometric Least Squares Mean (90% Confidence Interval) [Liters per Hour] |
16.26
|
14.51
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS mean |
Estimated Value | 0.892 | |
Confidence Interval |
(2-Sided) 90% 0.782 to 1.018 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 3: Cmin of Midazolam in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Geometric Least Squares Mean (90% Confidence Interval) [Nanograms per milliliter] |
0.192
|
0.222
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS mean |
Estimated Value | 1.157 | |
Confidence Interval |
(2-Sided) 90% 0.876 to 1.528 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 3: T1/2 of Midazolam in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Geometric Least Squares Mean (90% Confidence Interval) [Hours] |
5.320
|
6.075
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS mean |
Estimated Value | 1.142 | |
Confidence Interval |
(2-Sided) 90% 1.016 to 1.283 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 3: Vz/F of Midazolam in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Geometric Least Squares Mean (90% Confidence Interval) [Liters] |
615.36
|
371.24
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS mean |
Estimated Value | 0.603 | |
Confidence Interval |
(2-Sided) 90% 0.521 to 0.699 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 3: CL/F of Midazolam in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of midazolam was conducted using standard non-compartmental analysis. Analysis was performed using a linear mixed-effect model with treatment as a fixed effect and participant as a random effect. Geometric LS mean and 90 % CI of the geometric LS means have been presented. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Geometric Least Squares Mean (90% Confidence Interval) [Liters per Hour] |
80.17
|
42.16
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Cohort 1: Gepotidacin 1500 mg, Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Ratio of Geometric LS mean |
Estimated Value | 0.526 | |
Confidence Interval |
(2-Sided) 90% 0.448 to 0.618 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Cohort 3: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose ) |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 18 |
Geometric Mean (Geometric Coefficient of Variation) [Milligrams] |
1066.21
(40.4)
|
Title | Cohort 3: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose) |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles). |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 18 |
Ae (0-2), n=17 |
NA
(NA)
|
Ae (2-4), n=18 |
117.61
(101.7)
|
Ae (4-6), n=16 |
103.11
(57.3)
|
Ae (6-8); n=16 |
70.98
(53.7)
|
Ae (8-12), n=18 |
67.42
(44.3)
|
Ae (12-14), n=17 |
64.49
(94.1)
|
Ae (14-16), n=15 |
142.36
(142.3)
|
Ae (16-18), n=14 |
146.89
(59.4)
|
Ae (18-20), n=15 |
93.05
(83.5)
|
Ae (20-24), n=17 |
74.44
(93.9)
|
Ae (24-36), n=18 |
70.01
(105.0)
|
Ae (36-48); n=18 |
20.16
(46.4)
|
Ae (48-60), n=18 |
8.51
(42.7)
|
Title | Cohort 3: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose) |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 18 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
4770.8
(55.2)
|
Title | Cohort 3: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose) |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 18 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
14333.9
(59.2)
|
Title | Cohort 3: AUC (0-48) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose) |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 18 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
16682.1
(59.4)
|
Title | Cohort 3: Percentage of the Given Dose of Drug Excreted in Urine (fe%) Following Two 3000 mg Doses of Gepotidacin (First Dose + Second Dose ) |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 18 |
Geometric Mean (Geometric Coefficient of Variation) [Percent dose excreted] |
17.77
(40.4)
|
Title | Cohort 3: CLr of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose) |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population. Only those participants with data available at specified time points were analyzed. |
Arm/Group Title | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|
Arm/Group Description | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 17 |
Geometric Mean (Geometric Coefficient of Variation) [Liters per Hour] |
13.19
(34.6)
|
Title | Cohort 3: Number of Participants With SAE and Non-SAE |
---|---|
Description | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is defined as any serious adverse event that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situations as per Medical or scientific judgment. |
Time Frame | Up to 30 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Any SAE |
0
0%
|
0
0%
|
Any non-SAE |
1
7.1%
|
11
64.7%
|
Title | Cohort 3: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | Blood samples were collected at indicated time points for analysis of hematology parameters including Basophils, Eosinophils, MCH, MCV, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. |
Time Frame | Up to 30 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Basophils; To Low |
0
0%
|
0
0%
|
Basophils; To Normal or No Change |
19
135.7%
|
18
105.9%
|
Basophils; To High |
0
0%
|
0
0%
|
Eosinophils; To Low |
0
0%
|
0
0%
|
Eosinophils; To Normal or No Change |
19
135.7%
|
16
94.1%
|
Eosinophils; To High |
0
0%
|
2
11.8%
|
MCH; To Low |
0
0%
|
0
0%
|
MCH; To Normal or No Change |
19
135.7%
|
18
105.9%
|
MCH; To High |
0
0%
|
0
0%
|
MCV; To Low |
0
0%
|
0
0%
|
MCV; To Normal or No Change |
18
128.6%
|
18
105.9%
|
MCV; To High |
1
7.1%
|
0
0%
|
Erythrocytes; To Low |
2
14.3%
|
1
5.9%
|
Erythrocytes; To Normal or No Change |
17
121.4%
|
17
100%
|
Erythrocytes; To High |
0
0%
|
0
0%
|
Hematocrit; To Low |
1
7.1%
|
2
11.8%
|
Hematocrit; To Normal or No Change |
17
121.4%
|
14
82.4%
|
Hematocrit; To High |
1
7.1%
|
2
11.8%
|
Hemoglobin; To Low |
0
0%
|
1
5.9%
|
Hemoglobin; To Normal or No Change |
18
128.6%
|
15
88.2%
|
Hemoglobin; To High |
1
7.1%
|
2
11.8%
|
Leukocytes; To Low |
0
0%
|
0
0%
|
Leukocytes; To Normal or No Change |
19
135.7%
|
17
100%
|
Leukocytes; To High |
0
0%
|
1
5.9%
|
Lymphocytes; To Low |
0
0%
|
0
0%
|
Lymphocytes; To Normal or No Change |
19
135.7%
|
17
100%
|
Lymphocytes; To High |
0
0%
|
1
5.9%
|
Monocytes; To Low |
0
0%
|
1
5.9%
|
Monocytes; To Normal or No Change |
18
128.6%
|
17
100%
|
Monocytes; To High |
1
7.1%
|
0
0%
|
Neutrophils; To Low |
0
0%
|
0
0%
|
Neutrophils; To Normal or No Change |
19
135.7%
|
17
100%
|
Neutrophils; To High |
0
0%
|
1
5.9%
|
Platelets; To Low |
0
0%
|
0
0%
|
Platelets; To Normal or No Change |
19
135.7%
|
18
105.9%
|
Platelets; To High |
0
0%
|
0
0%
|
Title | Cohort 3: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | Blood samples were collected at indicated time points for analysis of clinical chemistry parameters including ALT, Albumin, Alk Phos, AST, Bilirubin, Calcium, Carbon Dioxide, Chloride, Creatine Kinase, Creatinine, Direct Bilirubin, Glucose, Magnesium, Potassium, Protein, Sodium, BUN. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. |
Time Frame | Up to 30 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
ALT; To Low |
0
0%
|
0
0%
|
ALT; To Normal or No Change |
19
135.7%
|
17
100%
|
ALT; To High |
0
0%
|
1
5.9%
|
Albumin; To Low |
1
7.1%
|
0
0%
|
Albumin; To Normal or No Change |
18
128.6%
|
17
100%
|
Albumin; To High |
0
0%
|
1
5.9%
|
Alk Phos; To Low |
0
0%
|
0
0%
|
Alk Phos; To Normal or No Change |
19
135.7%
|
18
105.9%
|
Alk Phos; To High |
0
0%
|
0
0%
|
AST; To Low |
0
0%
|
0
0%
|
AST; To Normal or No Change |
18
128.6%
|
18
105.9%
|
AST; To High |
1
7.1%
|
0
0%
|
Bilirubin; To Low |
0
0%
|
0
0%
|
Bilirubin; To Normal or No Change |
19
135.7%
|
18
105.9%
|
Bilirubin; To High |
0
0%
|
0
0%
|
Calcium; To Low |
1
7.1%
|
1
5.9%
|
Calcium; To Normal or No Change |
18
128.6%
|
17
100%
|
Calcium; To High |
0
0%
|
0
0%
|
Carbon Dioxide; To Low |
0
0%
|
0
0%
|
Carbon Dioxide; To Normal or No Change |
19
135.7%
|
18
105.9%
|
Carbon Dioxide; To High |
0
0%
|
0
0%
|
Chloride; To Low |
0
0%
|
0
0%
|
Chloride; To Normal or No Change |
19
135.7%
|
17
100%
|
Chloride; To High |
0
0%
|
1
5.9%
|
Creatine Kinase; To Low |
0
0%
|
0
0%
|
Creatine Kinase; To Normal or No Change |
18
128.6%
|
18
105.9%
|
Creatine Kinase; To High |
1
7.1%
|
0
0%
|
Creatinine; To Low |
0
0%
|
0
0%
|
Creatinine; To Normal or No Change |
19
135.7%
|
18
105.9%
|
Creatinine; To High |
0
0%
|
0
0%
|
Direct Bilirubin; To Low |
0
0%
|
0
0%
|
Direct Bilirubin; To Normal or No Change |
19
135.7%
|
18
105.9%
|
Direct Bilirubin; To High |
0
0%
|
0
0%
|
Glucose; To Low |
0
0%
|
0
0%
|
Glucose; To Normal or No Change |
19
135.7%
|
18
105.9%
|
Glucose; To High |
0
0%
|
0
0%
|
Magnesium; To Low |
0
0%
|
0
0%
|
Magnesium; To Normal or No Change |
19
135.7%
|
18
105.9%
|
Magnesium; To High |
0
0%
|
0
0%
|
Potassium; To Low |
0
0%
|
0
0%
|
Potassium; To Normal or No Change |
18
128.6%
|
18
105.9%
|
Potassium; To High |
1
7.1%
|
0
0%
|
Protein; To Low |
0
0%
|
0
0%
|
Protein; To Normal or No Change |
19
135.7%
|
18
105.9%
|
Protein; To High |
0
0%
|
0
0%
|
Sodium; To Low |
0
0%
|
0
0%
|
Sodium; To Normal or No Change |
19
135.7%
|
18
105.9%
|
Sodium; To High |
0
0%
|
0
0%
|
BUN; To Low |
0
0%
|
1
5.9%
|
BUN; To Normal or No Change |
19
135.7%
|
17
100%
|
BUN; To High |
0
0%
|
0
0%
|
Title | Cohort 3: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | Urine samples were collected at indicated time points for the analysis of urinalysis parameters including pH of urine, presence of glucose, protein, blood, ketones, bilirubin, nitrite, leukocyte esterase in urine by dipstick. Specific gravity of urine was measured by microscopic examination. Participants were counted in the worst case category that their value changes to (low, normal, high, or abnormal), unless there is no change in their category. Participants whose lab value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant has values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. |
Time Frame | Up to 30 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
Bilirubin; To Normal or No Change |
19
135.7%
|
18
105.9%
|
Bilirubin; To Abnormal |
0
0%
|
0
0%
|
Glucose; To Normal or No Change |
19
135.7%
|
18
105.9%
|
Glucose; To Abnormal |
0
0%
|
0
0%
|
Ketones; To Normal or No Change |
16
114.3%
|
17
100%
|
Ketones; To Abnormal |
3
21.4%
|
1
5.9%
|
Leukocyte Esterase; To Normal or No Change |
13
92.9%
|
13
76.5%
|
Leukocyte Esterase; To Abnormal |
6
42.9%
|
5
29.4%
|
Nitrite; To Normal or No Change |
19
135.7%
|
18
105.9%
|
Nitrite; To Abnormal |
0
0%
|
0
0%
|
Occult Blood; To Normal or No Change |
14
100%
|
13
76.5%
|
Occult Blood; To Abnormal |
5
35.7%
|
5
29.4%
|
Protein; To Normal or No Change |
16
114.3%
|
16
94.1%
|
Protein; To Abnormal |
3
21.4%
|
2
11.8%
|
pH; To Low |
0
0%
|
0
0%
|
pH; To Normal or No Change |
19
135.7%
|
18
105.9%
|
pH; To High |
0
0%
|
0
0%
|
Specific Gravity; To Low |
0
0%
|
0
0%
|
Specific Gravity; To Normal or No Chan |
16
114.3%
|
10
58.8%
|
Specific Gravity; To High |
3
21.4%
|
8
47.1%
|
Title | Cohort 3: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline |
---|---|
Description | Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest. Participants were counted in the worst case category that their value changes to (low, normal or high), unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category. Participants were counted twice if the participant had values that changed 'To Low' and 'To High', so the percentages may not add to 100%. High and low indicated that participants had values flagged as high and low respectively for the particular parameter any time on-treatment. |
Time Frame | Up to 30 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
DBP; To Low |
0
0%
|
0
0%
|
DBP; To Normal or No Change |
19
135.7%
|
18
105.9%
|
DBP; To High |
0
0%
|
0
0%
|
SBP; To Low |
0
0%
|
0
0%
|
SBP; To Normal or No Change |
19
135.7%
|
18
105.9%
|
SBP; To High |
0
0%
|
0
0%
|
Pulse rate; To Low |
0
0%
|
0
0%
|
Pulse rate; To Normal or No Change |
19
135.7%
|
18
105.9%
|
Pulse rate; To High |
0
0%
|
0
0%
|
Title | Cohort 3: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval |
---|---|
Description | A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes using an ECG machine that automatically calculated the QTc interval. Number of participants with any increase of >450 milliseconds in corrected QT interval using the QTcB Interval and QTcF Interval has been reported. |
Time Frame | Up to 30 days |
Outcome Measure Data
Analysis Population Description |
---|
Safety Population |
Arm/Group Title | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg |
---|---|---|
Arm/Group Description | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. |
Measure Participants | 19 | 18 |
QTcB Interval |
2
14.3%
|
5
29.4%
|
QTcF Interval |
0
0%
|
0
0%
|
Title | Cohort 4: T1/2 of Gepotidacin Following Single Dose of 1500 mg in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted |
---|---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Hours] |
12.848
(28.5)
|
12.540
(14.2)
|
Title | Cohort 4: Vz/F of Gepotidacin Following Single Dose of 1500 mg in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted |
---|---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Liters] |
1246.70
(38.8)
|
1329.83
(17.7)
|
Title | Cohort 4: CL/F of Gepotidacin Following Single Dose of 1500 mg in Plasma |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hour, 2 Hours 30 minutes, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 24 Hours, 36 Hours, 48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted |
---|---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Liters per Hour] |
67.26
(15.5)
|
73.50
(13.3)
|
Title | Cohort 4: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)-Fed State |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 11 |
Median (Full Range) [Hours] |
0
|
Title | Cohort 4: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population. Only those participants with data available at specified time points were analyzed. |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 10 |
Geometric Mean (Geometric Coefficient of Variation) [Liters] |
1251.05
(34.5)
|
Title | Cohort 4: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population. Only those participants with data available at specified time points were analyzed. |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 10 |
Geometric Mean (Geometric Coefficient of Variation) [Liters per Hour] |
68.83
(13.9)
|
Title | Cohort 4: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose )-Fed State |
---|---|
Description | Blood samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 30 minutes, 1 Hour, 1 Hour 30 minutes, 2 Hours, 2 Hours 30 minutes, 3, 4, 6, 8, 12 Hours, 12 Hours 30 minutes, 13 Hours, 13 Hours 30 minutes, 14 Hours, 14 Hours 30 minutes, 15, 16, 18, 20, 24, 36, 48, 60 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population. Only those participants with data available at specified time points were analyzed. |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 10 |
Geometric Mean (Geometric Coefficient of Variation) [Hours] |
12.599
(36.6)
|
Title | Cohort 4: Ae Total of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed |
---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Milligrams] |
293.50
(29.0)
|
Title | Cohort 4: Ae(t1-t2) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed |
---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 |
Ae (0-2) |
NA
(NA)
|
Ae (2-4) |
102.23
(25.2)
|
Ae (4-6) |
60.05
(57.0)
|
Ae (6-8) |
31.61
(48.9)
|
Ae (8-12) |
16.51
(97.0)
|
Ae (12-24) |
17.16
(49.3)
|
Ae (24-36) |
5.72
(196.5)
|
Ae (36-48) |
4.28
(63.2)
|
Title | Cohort 4: AUC(0-24) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed |
---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
2142.4
(53.5)
|
Title | Cohort 4: AUC(0-48) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed |
---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
2293.7
(53.2)
|
Title | Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) for Gepotidacin 1500 mg Under Fed Condition |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100%. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed |
---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Percent dose excreted] |
19.57
(29.0)
|
Title | Cohort 4: CLr of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed |
---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Liters per Hour] |
13.42
(31.9)
|
Title | Cohort 4: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Milligrams] |
1334.42
(25.4)
|
Title | Cohort 4: Ae(t1-t2) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles). |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 11 |
Ae (0-2); n=11 |
NA
(NA)
|
Ae (2-4); n=10 |
221.19
(56.7)
|
Ae (4-6); n=11 |
103.68
(70.6)
|
Ae (6-8); n=11 |
67.58
(49.5)
|
Ae (8-12); n=11 |
65.06
(22.7)
|
Ae (12-14); n=11 |
112.83
(66.3)
|
Ae (14-16); n=11 |
174.62
(85.2)
|
Ae (16-18); n=11 |
136.66
(68.1)
|
Ae (18-20); n=11 |
90.81
(25.4)
|
Ae (20-24); n=11 |
80.54
(20.4)
|
Ae (24-36); n=11 |
57.62
(42.9)
|
Ae (36-48); n=11 |
14.47
(36.9)
|
Ae (48-60); n=10 |
9.67
(61.7)
|
Title | Cohort 4: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population. Only those participants with data available at specified time points were analyzed. |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 10 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
4996.9
(64.4)
|
Title | Cohort 4: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population. Only those participants with data available at specified time points were analyzed. |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 10 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
14729.5
(59.3)
|
Title | Cohort 4: AUC(0-48) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population. Only those participants with data available at specified time points were analyzed. |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 10 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
15768.2
(58.8)
|
Title | Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin Following Two 3000 mg Doses-Fed State |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. fe% was calculated as: (Ae total divided by Dose) multiplied by 100 %. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Percent dose excreted] |
22.24
(25.4)
|
Title | Cohort 4: CLr of Gepotidacin Following Two 3000 mg Dose-Fed State |
---|---|
Description | Urine samples were collected at indicated time points. Pharmacokinetic analysis of gepotidacin was conducted using standard non-compartmental analysis. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-14 Hours, 14-16 Hours, 16-18 Hours, 18-20 Hours, 20-24 Hours, 24-36 Hours, 36-48 Hours, 48-60 Hours post-dose in Treatment Period 3 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population |
Arm/Group Title | Cohort 4: Gepotidacin 3000 mg Fed |
---|---|
Arm/Group Description | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on Day 1 of Period 3 in Cohort 4. |
Measure Participants | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Liters per Hour] |
14.61
(19.3)
|
Title | Cohort 4: AUC(0-tau) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine |
---|---|
Description | Urine samples were collected at indicated time points. AUC(0-tau) can be calculated only for multiple doses and not for single dose as tau refers to the dosing interval. Hence, AUC(0-tau) could not be calculated for Gepotidacin 1500 mg single dose as mentioned in Reporting and Analysis Plan. The results for this outcome measure will never be posted. |
Time Frame | Pre-dose, 0-2 Hours, 2-4 Hours, 4-6 Hours, 6-8 Hours, 8-12 Hours, 12-24 Hours, 24-36 Hours, 36-48 Hours post-dose in each Treatment Periods 1 and 2 |
Outcome Measure Data
Analysis Population Description |
---|
Pharmacokinetic Parameter Population. This was an other pre-specified outcome measure. The results for this outcome measure will never be posted. |
Arm/Group Title | Cohort 4: Gepotidacin 1500 mg Fed |
---|---|
Arm/Group Description | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. |
Measure Participants | 11 |
Geometric Mean (Geometric Coefficient of Variation) [Hours*micrograms per milliliter] |
NA
(NA)
|
Adverse Events
Time Frame | Serious adverse events (SAE) and non-serious adverse events (non-SAE) were collected up to 17 days during Cohort 1; up to 26 days during Cohort 2; up to 30 days during Cohort 3 and up to 22 days during Cohort 4. | |||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | Safety Population comprised of all participants who took at least 1 dose of study intervention. Participants with adverse events that occurred during Days 1 to 7 in Period 2 after the exposure of Rifampicin 600 mg and those occurred during Days 8 to 9 in Period 2 after exposure of Gepotidacin 1500 mg + Rifampicin 600 mg were summarized separately. Only those participants with data available at specified time points were analyzed. | |||||||||||||||||||||
Arm/Group Title | Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg | Cohort 2: Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2 (Days 1 to 7) Rifampicin 600 mg | Cohort 2: Period 2 (Days 8 to 9) Gepotidacin 1500 mg + Rifampicin 600 mg | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg | Cohort 4: Placebo | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted | Cohort 4: Gepotidacin 3000 mg Fed | |||||||||||
Arm/Group Description | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 1. | Participants received cimetidine 400 mg 4 times daily on Days 1 through 4 of Period 2 along with a single dose of gepotidacin 1500 mg administered one hour after the first dose of cimetidine on Day 2 of Period 2 in Cohort 1. | Participants received a single oral dose of gepotidacin 1500 mg on Day 1 of Period 1 in Cohort 2. | Participants received rifampicin 600 mg (administered in the evenings) once daily for 7 days (Days 1 through 7) of Period 2 in Cohort 2. | Participants received a single dose of gepotidacin 1500 mg administered in the morning on Day 8 and rifampicin 600 mg administered in the evening on Days 8 and 9 of Period 2 in Cohort 2. | Participants received digoxin 0.5 mg and midazolam 2 mg on Day 1 of Period 1 and Period 2 in Cohort 3. | Participants received two doses of gepotidacin 3000 mg given 12 hours apart along with co-administration of digoxin 0.5 mg and midazolam 2 mg with the second dose of gepotidacin on Day 1 of Period 1 and Period 2 in Cohort 3. | Japanese participants received a single oral dose of placebo matching gepotidacin under fed conditions in Period 1 or a single dose of placebo matching gepotidacin under fasted conditions in Period 2 or two doses of placebo (given 12 hours apart) matching gepotidacin under fed conditions in Period 3 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fed conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received a single dose of gepotidacin 1500 mg under fasted conditions on Day 1 of Period 1 and Period 2 in Cohort 4. | Japanese participants received two doses of gepotidacin 3000 mg (given 12 hours apart) under fed conditions on on Day 1 of Period 3 in Cohort 4. | |||||||||||
All Cause Mortality |
||||||||||||||||||||||
Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg | Cohort 2: Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2 (Days 1 to 7) Rifampicin 600 mg | Cohort 2: Period 2 (Days 8 to 9) Gepotidacin 1500 mg + Rifampicin 600 mg | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg | Cohort 4: Placebo | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted | Cohort 4: Gepotidacin 3000 mg Fed | ||||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/14 (0%) | 0/13 (0%) | 0/17 (0%) | 0/17 (0%) | 0/14 (0%) | 0/19 (0%) | 0/18 (0%) | 0/3 (0%) | 0/11 (0%) | 0/11 (0%) | 0/11 (0%) | |||||||||||
Serious Adverse Events |
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Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg | Cohort 2: Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2 (Days 1 to 7) Rifampicin 600 mg | Cohort 2: Period 2 (Days 8 to 9) Gepotidacin 1500 mg + Rifampicin 600 mg | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg | Cohort 4: Placebo | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted | Cohort 4: Gepotidacin 3000 mg Fed | ||||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/14 (0%) | 0/13 (0%) | 0/17 (0%) | 0/17 (0%) | 0/14 (0%) | 0/19 (0%) | 0/18 (0%) | 0/3 (0%) | 0/11 (0%) | 0/11 (0%) | 0/11 (0%) | |||||||||||
Other (Not Including Serious) Adverse Events |
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Cohort 1: Gepotidacin 1500 mg | Cohort 1: Gepotidacin 1500 mg + Cimetidine 400 mg | Cohort 2: Period 1: Gepotidacin 1500 mg | Cohort 2: Period 2 (Days 1 to 7) Rifampicin 600 mg | Cohort 2: Period 2 (Days 8 to 9) Gepotidacin 1500 mg + Rifampicin 600 mg | Cohort 3: Digoxin 0.5 mg + Midazolam 2 mg | Cohort 3:Gepotidacin 3000 mg + Digoxin 0.5 mg + Midazolam 2 mg | Cohort 4: Placebo | Cohort 4: Gepotidacin 1500 mg Fed | Cohort 4: Gepotidacin 1500 mg Fasted | Cohort 4: Gepotidacin 3000 mg Fed | ||||||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/14 (0%) | 0/13 (0%) | 3/17 (17.6%) | 2/17 (11.8%) | 2/14 (14.3%) | 1/19 (5.3%) | 11/18 (61.1%) | 0/3 (0%) | 1/11 (9.1%) | 2/11 (18.2%) | 4/11 (36.4%) | |||||||||||
Gastrointestinal disorders | ||||||||||||||||||||||
Diarrhoea | 0/14 (0%) | 0 | 0/13 (0%) | 0 | 2/17 (11.8%) | 2 | 0/17 (0%) | 0 | 2/14 (14.3%) | 2 | 0/19 (0%) | 0 | 6/18 (33.3%) | 6 | 0/3 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 3/11 (27.3%) | 3 |
Nausea | 0/14 (0%) | 0 | 0/13 (0%) | 0 | 1/17 (5.9%) | 1 | 2/17 (11.8%) | 2 | 0/14 (0%) | 0 | 0/19 (0%) | 0 | 4/18 (22.2%) | 4 | 0/3 (0%) | 0 | 1/11 (9.1%) | 1 | 2/11 (18.2%) | 2 | 2/11 (18.2%) | 2 |
Investigations | ||||||||||||||||||||||
Electrocardiogram T wave abnormal | 0/14 (0%) | 0 | 0/13 (0%) | 0 | 0/17 (0%) | 0 | 0/17 (0%) | 0 | 0/14 (0%) | 0 | 1/19 (5.3%) | 1 | 2/18 (11.1%) | 2 | 0/3 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 |
Nervous system disorders | ||||||||||||||||||||||
Headache | 0/14 (0%) | 0 | 0/13 (0%) | 0 | 2/17 (11.8%) | 2 | 1/17 (5.9%) | 1 | 0/14 (0%) | 0 | 0/19 (0%) | 0 | 0/18 (0%) | 0 | 0/3 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 | 0/11 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title | GSK Response Center |
---|---|
Organization | GlaxoSmithKline |
Phone | 866-435-7343 |
GSKClinicalSupportHD@gsk.com |
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