Pharmacokinetics of Gepotidacin Tablets in Adults and Adolescents Subjects

Phase 1

Completed

Conditions: Infections, Bacterial

Interventions: Drug: Placebo
Drug: Gepotidacin

Registration Number: NCT04079790

Lead Sponsor: GlaxoSmithKline

Brief Summary: This is double-blind, randomized, sequential, two part study. Part 1 is a 3 periods, fixed-sequence study and will be conducted to evaluate the pharmacokinetics, safety, and tolerability of the gepotidacin tablet in healthy adult subjects. Part 2 is a 2 periods, fixed-sequence study and will evaluate the pharmacokinetics, safety, and tolerability of the gepotidacin tablet in healthy adolescent subjects. The primary purpose of Part 1 is to evaluate the pharmacokinetics of a single 1500 milligram (mg) dose and two 3000 mg doses of gepotidacin given 6 and 12 hours apart in adult subjects; Part 2 is to evaluate the pharmacokinetics of a single 1500 mg dose and two 3000 mg doses of gepotidacin given at a dosing interval (to be determined based on the pharmacokinetic and safety results from Part 1) in adolescent subjects. The duration of Part A will be approximately 47 days and 52 days for Part 2.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 34

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Subjects receiving Placebo in Part 1	Placebo	Healthy adult subjects will receive a single oral dose of matching placebo (treatment B), tablets, on Day 1 of Period 1; two oral doses of matching placebo (treatment D), tablets, at 0 and 12 hours on Day 5 of Period 2; and two oral doses of matching placebo (treatment F), tablets, at 0 and 6 hours on Day 9 of Period 3.
Subjects receiving Placebo in Part 2	Placebo	Healthy adolescent subjects will receive a single oral dose of matching placebo (treatment B), tablets on Day 1 of Period 1; and two oral doses of matching placebo (treatment H), tablets at 0 and 6 hours on Day 1 of Period 2.
Subjects receiving Gepotidacin in Part 2	Gepotidacin	Healthy adolescent subjects will receive a single oral dose of gepotidacin 1500 mg (2 x 750 mg, treatment A), tablets, on Day 1 of Period 1; and two oral doses of gepotidacin 3000 mg (4 x 750 mg, treatment G), tablets, at 0 and 6 hours on Day 1 of Period 2.
Subjects receiving Gepotidacin in Part 1	Gepotidacin	Healthy adult subjects will receive a single oral dose of gepotidacin 1500 mg (2 X 750 mg, treatment A), tablets, on Day 1 of Period 1; two oral doses of gepotidacin 3000 mg (4 x 750 mg, Treatment C), tablets, at 0 and 12 hours on Day 5 of Period 2; and two oral doses of gepotidacin 3000 mg (4 x 750 mg, treatment E), tablets, at 0 and 6 hours on Day 9 of Period 3.

Primary Outcome Measures

Name	Time	Method
Part 1- Period 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to Time of the Last Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 1- Period 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 1- Period 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to 24 Hours Post-dose (AUC[0-24]) After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 1- Period 3: RoAUC Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 6.5, 7, 7.5, 8, 8.5, 9, 10, 12, 14, 18, 24, 36, 48 and 60 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed 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.
Part 1- Period 2: Cmax Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, 24, 36, 48 and 60 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 1- Period 2: AUC(0-t) Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, 24, 36, 48 and 60 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 1- Period 2: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to Time Tau (Tau=12) (AUC[0-tau]) Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 1- Period 2: AUC(0-24) Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20 and 24 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 1- Period 3: AUC(0-24) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 6.5, 7, 7.5, 8, 8.5, 9, 10, 12, 14, 18 and 24 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 1- Period 3: AUC(0-48) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 6.5, 7, 7.5, 8, 8.5, 9, 10, 12, 14, 18, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 1- Period 2: Accumulation Ratio for AUC (RoAUC) Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, 24, 36, 48 and 60 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed 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.
Part 1: Number of Participants With Urinalysis Toxicities of Grade 3 or Higher	Up to Day 19	Urine samples were collected for the analysis of urine parameters including specific gravity, potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase. Toxicities were graded using the Division of Microbiology and Infectious Diseases toxicity grading where Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4=Life-threatening. Number of participants with a grade 3 or higher toxicity for any of the urine parameter is presented
Part 1- Period 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to 48 Hours Post-dose (AUC[0-48]) After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 1- Period 1: Maximum Observed Concentration (Cmax) After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 1- Period 3: AUC(0-t) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 6.5, 7, 7.5, 8, 8.5, 9, 10, 12, 14, 18, 24, 36, 48 and 60 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 1- Period 3: AUC(0-tau) (Tau=6) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4 and 6 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin.PK parameters were analyzed using standard non-compartmental analysis.
Part 1- Period 2: AUC(0-48) Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 2: Period 1: Number of Participants With Abnormal 12-lead ECG Findings	Predose, predose 2, predose 3, 0.5. 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours on Day 1, 24, 36 hours on Day 2 and 48 hours on Day 3	A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes. Twelve lead ECGs were obtained by using an automated ECG machine that measured PR, QRS, QT, and QTc intervals and calculated heart rate. Data for abnormal NCS and CS were presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Part 1- Period 2: Accumulation Ratio for Cmax (RoCmax) Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, 24, 36, 48 and 60 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose.
Part 1- Period 3: RoCmax Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 6.5, 7, 7.5, 8, 8.5, 9, 10, 12, 14, 18, 24, 36, 48 and 60 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis. Accumulation ratio was calculated as Cmax after the second dose divided by Cmax after the first dose.
Part 1- Period 3: Cmax Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 6.5, 7, 7.5, 8, 8.5, 9, 10, 12, 14, 18, 24, 36, 48 and 60 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 2- Period 1: AUC(0-24) After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 2- Period 1: Cmax After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 2- Period 1: AUC(0-t) After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 2- Period 1: AUC(0-infinity) After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 2- Period 2: AUC(0-24) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 6.5, 7, 7.5, 8, 8.5, 9, 10, 12, 14, 18 and 24 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis
Part 2- Period 2: Cmax Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 6.5, 7, 7.5, 8, 8.5, 9, 10, 12, 14, 18, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)	Up to Day 19	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 any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of participants with common (\>=5%) non-serious AEs and SAEs is presented.
Part 2: Number of Participants With Non-serious AEs and SAEs	Up to Day 21	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 any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of participants with common (\>=5%) non-serious AEs and SAEs are presented.
Part 2- Period 1: AUC(0-48) After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 2- Period 2: AUC(0-t) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 6.5, 7, 7.5, 8, 8.5, 9, 10, 12, 14, 18, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 2- Period 2: AUC(0-tau) (Tau=6) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4 and 6 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.
Part 2- Period 2: AUC(0-48) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 6.5, 7, 7.5, 8, 8.5, 9, 10, 12, 14, 18, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis
Part 1: Number of Participants With Hematology Toxicities of Grade 3 or Higher	Up to Day 19	Blood samples were collected for the analysis of following hematology parameters: platelet count, red blood cell (RBC) count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), white blood cell (WBC) count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. The hematology abnormalities were graded using the Division of Microbiology and Infectious Diseases toxicity grading where Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4=Life-threatening. Number of participants with a grade 3 or higher toxicity for any of the hematology parameter is presented.
Part 2: Number of Participants With Hematology Toxicities of Grade 3 or Higher	Up to Day 21	Blood samples were collected for the analysis of following hematology parameters: platelet count, RBC count, hemoglobin, hematocrit, MCV, MCH, WBC count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. The hematology abnormalities were graded using the Division of Microbiology and Infectious Diseases toxicity grading where Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4=Life-threatening. Number of participants with a grade 3 or higher toxicity for any of the hematology parameter is presented.
Part 1: Number of Participants With Clinical Chemistry Toxicities of Grade 3 or Higher	Up to Day 19	Blood samples were collected for the analysis of following clinical chemistry parameters: blood urea nitrogen (BUN), creatinine, glucose (fasting), potassium, sodium, magnesium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total and direct bilirubin, creatine phosphokinase, calcium, chloride, carbon dioxide, total protein and albumin. The clinical chemistry abnormalities were graded using the Division of Microbiology and Infectious Diseases toxicity grading where Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4=Life-threatening. Number of participants with a grade 3 or higher toxicity for any of the clinical chemistry parameter is presented
Part 2: Number of Participants With Clinical Chemistry Toxicities of Grade 3 or Higher	Up to Day 21	Blood samples were collected for the analysis of following clinical chemistry parameters: BUN, creatinine, glucose (fasting), potassium, sodium, magnesium, AST, ALT, alkaline phosphatase, total and direct bilirubin, creatine phosphokinase, calcium, chloride, carbon dioxide, total protein and albumin. The clinical chemistry abnormalities were graded using the Division of Microbiology and Infectious Diseases toxicity grading where Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4=Life-threatening. Number of participants with a grade 3 or higher toxicity for any of the clinical chemistry parameter is presented
Part 2: Number of Participants With Urinalysis Toxicities of Grade 3 or Higher	Up to Day 21	Urine samples were collected for the analysis of urine parameters including specific gravity, pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase. Toxicities were graded using the Division of Microbiology and Infectious Diseases toxicity grading where Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe and Grade 4=Life-threatening. Number of participants with a grade 3 or higher toxicity for any of the urine parameter is presented
Part 1: Number of Participants With Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Potential Clinical Importance	Up to Day 19	SBP and DBP were measured in a semi-supine position after 5 minutes of rest. The potential clinically important range for vital signs were: SBP (lower: \<85 and upper: \>160 millimeters of mercury \[mmHg\]) and DBP (lower: \<45 and upper: \>100 mmHg).
Part 2: Number of Participants With SBP and DBP of Potential Clinical Importance	Up to Day 21	SBP and DBP were measured in a semi-supine position after 5 minutes of rest. The potential clinically important range for vital signs were: SBP (lower: \<85 and upper: \>160 mmHg) and DBP (lower: \<45 and upper: \>100 mmHg).
Part 1: Number of Participants With Abnormal Heart Rate of Potential Clinical Importance	Up to Day 19	Heart rate was measured in a semi-supine position after 5 minutes of rest. The potential clinically important range for heart rate was (lower:\<40 and upper: \>110 beats per minute).
Part 2: Number of Participants With Abnormal Heart Rate of Potential Clinical Importance	Up to Day 21	Heart rate was measured in a semi-supine position after 5 minutes of rest. The potential clinically important range for heart rate was (lower:\<40 and upper: \>110 beats per minute).
Part 1: Period 1: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings	Predose, predose 2, predose 3, 0.5. 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 hours on Day 1, 24, 36 hours on Day 2 and 48 hours on Day 3.	A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes. Twelve lead ECGs were obtained by using an automated ECG machine that measured PR, QRS, QT, and corrected QT (QTc) intervals and calculated heart rate. Data for abnormal not clinically significant (NCS) and clinically significant (CS) ECG findings are presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Part 1: Period 2: Number of Participants With Abnormal 12-lead ECG Findings	Predose, predose 2, predose 3, 0.5. 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20 hours on Day 1, 24, 36 hours on Day 2, 48 and 60 hours on Day 3	A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes. Twelve lead ECGs were obtained by using an automated ECG machine that measured PR, QRS, QT, and QTc intervals and calculated heart rate. Data for abnormal NCS and CS ECG findings are presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Part 1: Period 3: Number of Participants With Abnormal 12-lead ECG Findings	Predose, predose 2, predose 3, 0.5. 1, 1.5, 2, 2.5, 3, 4, 6, 6.5, 7, 7.5, 8, 8.5, 9, 10, 12, 14, 18 hours on Day 1, 24, 36 hours on Day 2, 48 and 60 hours on Day 3	A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes. Twelve lead ECGs were obtained by using an automated ECG machine that measured PR, QRS, QT, and QTc intervals and calculated heart rate. Data for abnormal NCS and CS ECG findings are presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Part 2: Period 2: Number of Participants With Abnormal 12-lead ECG Findings	Predose, predose 2, predose 3, 0.5. 1, 1.5, 2, 2.5, 3, 4, 6, 6.5, 7, 7.5, 8, 8.5, 9, 10, 12, 14, 18 hours on Day 1, 24, 36 hours on Day 2 and 48 hours on Day 3	A 12-lead ECG was recorded with the participant in a semi-supine position after a rest of at least 10 minutes. Twelve lead ECGs were obtained by using an automated ECG machine that measured PR, QRS, QT, and QTc intervals and calculated heart rate. Data for abnormal NCS and CS were presented CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Secondary Outcome Measures

Name	Time	Method
Part 1- Period 1: Total Unchanged Drug (Ae Total) After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-12, 12-24, 24-36 and 36-48 hours post-dose	Urine samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.
Part 1- Period 2: Ae(t1-t2) After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval	0-2, 2-4, 4-6, 6-8, 8-12, 12-14, 14-16, 16-18, 18-20, 20-24, 24-36, 36-48 and 48-60 hours post-dose	Urine samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals
Part 1- Period 3: Ae(t1-t2) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval	0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-14, 14-18, 18 -24, 24-36, 36-48 and 48-60 hours post-dose	Urine samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.
Part 1- Period 2: AUC(0-tau) (Tau=12 Hours Post-dose) After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval (Urine)	Pre-dose, 0-2, 2-4, 4-6, 6-8 and 8-12 hours post-dose	Urine samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin.
Part 1- Period 1: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) After Single Dose Administration of Gepotidacin 1500 mg	0-2, 2-4, 4-6, 6-8, 8-12, 12-24, 24-36 and 36-48 hours post-dose	Urine samples were collected at the specified intervals for PK analysis. PK parameters were calculated using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.
Part 1- Period 1: AUC(0-24) After Single Dose Administration of Gepotidacin 1500 mg (Urine)	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-12 and 12-24 hours post-dose.	Urine samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin.
Part 1- Period 2: AUC(0-24) After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval (Urine)	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-12, 12-14, 14-16, 16-18, 18-20 and 20-24 hours post dose	Urine samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin.
Part 1- Period 3: AUC(0-24) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval (Urine)	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-14, 14-18 and 18-24 hours post-dose	Urine samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin.
Part 1- Period 2: AUC(0-48) After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval (Urine)	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-12, 12-14, 14-16, 16-18, 18-20, 20-24, 24-36 and 36-48 hours post-dose	Urine samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin
Part 2- Period 1: Tlag After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were calculated using standard non-compartmental analysis.
Part 2- Period 1: t1/2 After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were calculated using standard non-compartmental analysis.
Part 1- Period 1: AUC(0-48) After Single Dose Administration of Gepotidacin 1500 mg (Urine)	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-12, 12-24, 24-36 and 36-48 hours post-dose	Urine samples were be collected at indicated time points for pharmacokinetic analysis of gepotidacin.
Part 1- Period 1: Percentage of the Given Dose of Drug Excreted in Urine (fe%) After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-12, 12-24, 24-36 and 36-48 hours post-dose	Urine samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis. fe% was calculated as: (Ae total/Dose) x 100 percent (%).
Part 1- Period 1: Renal Clearance of Drug (CLr) After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-12, 12-24, 24-36 and 36-48 hours post-dose	Urine samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis. CLr was calculated as: Ae total/AUC(0-t)
Part 1- Period 2: Ae Total After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-12, 12-14, 14-16, 16-18, 18-20, 20-24, 24-36, 36-48 and 48-60 hours post-dose	Urine samples were collected at indicated time points. Ae total were calculated by adding all the fractions of drug collected over all the allotted time intervals.
Part 1- Period 3: Ae Total After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-14, 14-18, 18-24, 24-36, 36-48 and 48-60 hours post-dose	Urine samples were collected at indicated time points. Ae total were calculated by adding all the fractions of drug collected over all the allotted time intervals
Part 2- Period 1: Tmax After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were calculated using standard non-compartmental analysis.
Part 2- Period 2: Tmax After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 6.5, 7, 7.5, 8, 8.5, 9, 10, 12, 14, 18, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were calculated using standard non-compartmental analysis.
Part 2- Period 2: Tlag After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 6.5, 7, 7.5, 8, 8.5, 9, 10, 12, 14, 18, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were calculated using standard non-compartmental analysis.
Part 1- Period 3: AUC(0-tau) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval (Urine)	Pre-dose, 0-2, 2-4 and 4-6 hours post-dose	Urine samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin
Part 1- Period 3: AUC(0-48) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval (Urine)	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-14, 14-18, 18-24, 24-36 and 36-48 hours post-dose	Urine samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin
Part 1- Period 2: fe% After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-12, 12-14, 14-16, 16-18, 18-20, 20-24, 24-36, 36-48 and 48-60 hours post-dose	Urine samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis. fe% was calculated as: (Ae total/Dose) x 100%.
Part 1- Period 3: fe% After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-14, 14-18, 18-24, 24-36, 36-48 and 48-60 hours post-dose	Urine samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis. fe% was calculated as: (Ae total/Dose) x 100%.
Part 1- Period 2: CLr After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-12, 12-14, 14-16, 16-18, 18-20, 20-24, 24-36, 36-48 and 48-60 hours post-dose	Urine samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis. CLr was calculated as: Ae total/AUC(0-t)
Part 1- Period 3: CLr After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-14, 14-18, 18-24, 24-36, 36-48 and 48-60 hours post-dose	Urine samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis. CLr was calculated as: Ae total/AUC(0-t)
Part 2- Period 1: Ae Total After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-12, 12-24, 24-36 and 36-48 hours post-dose	Urine samples were collected at indicated time points. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals
Part 2- Period 1: Ae(t1-t2) After Single Dose Administration of Gepotidacin 1500 mg	0-2, 2-4, 4-6, 6-8, 8-12, 12-24,24-36 and 36-48 hours post-dose	Urine samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.
Part 2- Period 1: AUC(0-24) After Single Dose Administration of Gepotidacin 1500 mg (Urine)	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-12 and 12-24 hours post-dose.	Urine samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin.
Part 2- Period 1: AUC(0-48) After Single Dose Administration of Gepotidacin 1500 mg (Urine)	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-12, 12-24, 24-36 and 36-48 hours post-dose	Urine samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin.
Part 2- Period 1: fe% After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-12, 12-24, 24-36 and 36-48 hours post-dose	Urine samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis. fe% was calculated as: (Ae total/Dose) x 100%.
Part 2- Period 1: CLr After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-12, 12-24, 24-36 and 36-48 hours post-dose	Urine samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis. CLr was calculated as: Ae total/AUC(0-t).
Part 2- Period 2: Ae Total After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-14, 14-18, 18-24, 24-36 and 36-48 hours post-dose	Urine samples were collected at indicated time points. Ae total was calculated by adding all the fractions of drug collected over all the allotted time intervals.
Part 2- Period 2: Ae(t1-t2) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval	0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-14, 14-18, 18-24, 24-36 and 36-48 hours post-dose	Urine samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis. Ae(t1-t2) measured the amount of drug excreted in urine at defined time intervals.
Part 2- Period 2: AUC(0-tau) (Tau=6 Hours Post-dose) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval (Urine)	Pre-dose, 0-2, 2-4, 4-6 hours post-dose	Urine samples will be collected at indicated time points for pharmacokinetic analysis of gepotidacin
Part 2- Period 2: AUC(0-24) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval (Urine)	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-14, 14-18 and 18-24 hours post-dose	Urine samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin.
Part 2- Period 2: AUC(0-48) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval (Urine)	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-14, 14-18, 18-24, 24-36 and 36-48 hours post-dose.	Urine samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin
Part 2- Period 2: fe% After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-14, 14-18, 18-24, 24-36 and 36-48 hours post-dose	Urine samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis. fe% was calculated as: (Ae total/Dose) x 100%.
Part 2- Period 2: CLr After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval	Pre-dose, 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-14, 14-18, 18-24, 24-36 and 36-48 hours post-dose	Urine samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis. CLr was calculated as: Ae total/AUC(0-t).
Part 1- Period 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were calculated using standard non-compartmental analysis.
Part 1- Period 1: Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were calculated using standard non-compartmental analysis.
Part 1- Period 1: Terminal Phase Half-life (t1/2) After Single Dose Administration of Gepotidacin 1500 mg	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were calculated using standard non-compartmental analysis.
Part 1- Period 2: Tmax After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, 24, 36, 48 and 60 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were calculated using standard non-compartmental analysis.
Part 1- Period 3: Tmax After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 6.5, 7, 7.5, 8, 8.5, 9, 10, 12, 14, 18, 24, 36, 48 and 60 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were calculated using standard non-compartmental analysis.
Part 2- Period 2: t1/2 After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 6.5, 7, 7.5, 8, 8.5, 9, 10, 12, 14, 18, 24, 36 and 48 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were calculated using standard non-compartmental analysis.
Part 1- Period 2: Tlag After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, 24, 36, 48 and 60 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were calculated using standard non-compartmental analysis.
Part 1- Period 3: Tlag After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 6.5, 7, 7.5, 8, 8.5, 9, 10, 12, 14, 18, 24, 36, 48 and 60 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were calculated using standard non-compartmental analysis.
Part 1- Period 2: t1/2 After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 12.5, 13, 13.5, 14, 14.5, 15, 16, 18, 20, 24, 36, 48 and 60 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were calculated using standard non-compartmental analysis.
Part 1- Period 3: t1/2 After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 6.5, 7, 7.5, 8, 8.5, 9, 10, 12, 14, 18, 24, 36, 48 and 60 hours post-dose	Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were calculated using standard non-compartmental analysis.