Pharmacokinetics of Gepotidacin Tablets in Adults and Adolescents Subjects

NCT04079790 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 209611
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Infections, Bacterial

Keywords

GSK2140944; Gepotidacin; Pharmacokinetics; Healthy Adult; Healthy adolescent

Outcome Measures

Primary Outcomes (46)

• 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

  Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose

• 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

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose

• 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

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 hours post-dose

• 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

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose

• Part 1- Period 1: Maximum Observed Concentration (Cmax) After Single Dose Administration of Gepotidacin 1500 mg

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose

• Part 1- Period 2: AUC(0-t) Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  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

• Part 1- Period 3: AUC(0-t) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  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

• 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

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8 and 12 hours post-dose

• Part 1- Period 3: AUC(0-tau) (Tau=6) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin.PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4 and 6 hours post-dose

• Part 1- Period 2: AUC(0-24) Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  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

• Part 1- Period 3: AUC(0-24) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  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

• Part 1- Period 2: AUC(0-48) Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  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

• Part 1- Period 3: AUC(0-48) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  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

• Part 1- Period 2: Accumulation Ratio for Cmax (RoCmax) Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval

  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.

  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

• Part 1- Period 2: Accumulation Ratio for AUC (RoAUC) Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval

  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.

  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

• Part 1- Period 3: RoCmax Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval

  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.

  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

• Part 1- Period 3: RoAUC Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval

  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.

  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

• Part 1- Period 2: Cmax Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  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

• Part 1- Period 3: Cmax Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  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

• Part 2- Period 1: AUC(0-t) After Single Dose Administration of Gepotidacin 1500 mg

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose

• Part 2- Period 1: AUC(0-infinity) After Single Dose Administration of Gepotidacin 1500 mg

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose

• Part 2- Period 1: AUC(0-24) After Single Dose Administration of Gepotidacin 1500 mg

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 hours post-dose

• Part 2- Period 1: AUC(0-48) After Single Dose Administration of Gepotidacin 1500 mg

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose

• Part 2- Period 1: Cmax After Single Dose Administration of Gepotidacin 1500 mg

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36 and 48 hours post-dose

• Part 2- Period 2: AUC(0-t) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Interval

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  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

• Part 2- Period 2: AUC(0-tau) (Tau=6) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Interval

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4 and 6 hours post-dose

• Part 2- Period 2: AUC(0-24) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Interval

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis

  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

• Part 2- Period 2: AUC(0-48) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Interval

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis

  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

• Part 2- Period 2: Cmax Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Interval

  Blood samples were collected at indicated time points for pharmacokinetic analysis of gepotidacin. PK parameters were analyzed using standard non-compartmental analysis.

  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

• Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)

  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.

  Up to Day 19

• Part 2: Number of Participants With Non-serious AEs and SAEs

  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.

  Up to Day 21

• Part 1: Number of Participants With Hematology Toxicities of Grade 3 or Higher

  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.

  Up to Day 19

• Part 2: Number of Participants With Hematology Toxicities of Grade 3 or Higher

  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.

  Up to Day 21

• Part 1: Number of Participants With Clinical Chemistry Toxicities of Grade 3 or Higher

  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

  Up to Day 19

• Part 2: Number of Participants With Clinical Chemistry Toxicities of Grade 3 or Higher

  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

  Up to Day 21

• Part 1: Number of Participants With Urinalysis Toxicities of Grade 3 or Higher

  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

  Up to Day 19

• Part 2: Number of Participants With Urinalysis Toxicities of Grade 3 or Higher

  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

  Up to Day 21

• Part 1: Number of Participants With Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Potential Clinical Importance

  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).

  Up to Day 19

• Part 2: Number of Participants With SBP and DBP of Potential Clinical Importance

  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).

  Up to Day 21

• Part 1: Number of Participants With Abnormal Heart Rate of Potential Clinical Importance

  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).

  Up to Day 19

• Part 2: Number of Participants With Abnormal Heart Rate of Potential Clinical Importance

  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).

  Up to Day 21

• Part 1: Period 1: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings

  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.

  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.

• Part 1: Period 2: Number of Participants With Abnormal 12-lead ECG Findings

  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.

  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

• Part 1: Period 3: Number of Participants With Abnormal 12-lead ECG Findings

  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.

  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

• Part 2: Period 1: Number of Participants With Abnormal 12-lead ECG Findings

  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.

  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

• Part 2: Period 2: Number of Participants With Abnormal 12-lead ECG Findings

  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.

  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

Secondary Outcomes (48)

• 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

• 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

• 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.

• 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

• 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

Study Arms (4)

Subjects receiving Gepotidacin in Part 1

EXPERIMENTAL

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.

Drug: Gepotidacin

Subjects receiving Placebo in Part 1

PLACEBO COMPARATOR

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.

Drug: Placebo

Subjects receiving Gepotidacin in Part 2

EXPERIMENTAL

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.

Drug: Gepotidacin

Subjects receiving Placebo in Part 2

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Gepotidacin DRUG

Tablets containing gepotidacin mesylate with a unit dose of 750 mg will be administered orally with 240 milliliter (mL) of water.

Subjects receiving Gepotidacin in Part 1; Subjects receiving Gepotidacin in Part 2

Placebo DRUG

Tablets containing unit dose of placebo matching of gepotidacin will be administered orally with 240 mL of water.

Subjects receiving Placebo in Part 1; Subjects receiving Placebo in Part 2

Eligibility Criteria

• Age: 12 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subjects in Part 1 must be \>=18 to \<=64 years of age inclusive, at the time of signing the informed consent.
• Subjects in Part 2 must be \>=12 to \<18 years of age inclusive, at the time of signing the informed consent/assent.
• Subjects 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 \<450 millisecond (msec). A subject 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.
• Body weight \>=40 kilogram (kg) and body mass index (BMI) within the range 18.5 - 32.0 kg per square meter (inclusive).
• Male and/or female.
• Female subjects: A female subject is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: a) Is not a woman of childbearing potential (WOCBP), or b) Is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of \<1% for at least 30 days prior to dosing until completion of the follow-up visit. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. A WOCBP must have a highly sensitive negative pregnancy test before the first dose of study intervention.
• Capable of giving signed informed consent/assent which includes compliance with the requirements and restrictions listed in the informed consent form/assent and protocol.

You may not qualify if:

• Clinically significant abnormality in the past medical history or at the screening physical examination that in the investigator's opinion may place the subject at risk or interfere with outcome variables of the study. This includes, but is not limited to, history or current cardiac, hepatic, renal, neurologic, gastrointestinal (GI), respiratory, hematologic, or immunologic disease.
• 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 subject at risk, in the opinion of the investigator.
• Female subject has a positive pregnancy test result or is lactating at screening or upon admission to the clinic.
• Use of any systemic antibiotic within 30 days of screening.
• Within 2 months before screening, either a confirmed history of Clostridium difficile diarrhea infection or a past positive of Clostridium difficile toxin test.
• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• 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.
• History of sensitivity to any of the study drug, components thereof, or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline medical monitor contraindicates their participation.
• History of sensitivity to heparin or heparin-induced thrombocytopenia (if the clinic uses heparin to maintain intravenous cannula patency).
• Subject must abstain from taking prescription or non-prescription drugs (except for hormonal contraceptives and/or acetaminophen), 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.
• Previous exposure to gepotidacin within 12 months prior to starting study intervention.
• Subject has participated in a clinical trial and has received an investigational product prior to gepotidacin administration within 30 days, 5 half-lives, or twice the duration of the biological effect of investigational product (whichever is longer).
• Presence of hepatitis B surface antigen or positive hepatitis C antibody test result at screening or within 3 months prior to starting study intervention.
• ALT \>1.5 \* upper limit of normal (ULN).
• Bilirubin \>1.5 \* ULN (isolated bilirubin \>1.5 \* ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Las Vegas, Nevada, 89113, United States

Location

Related Publications (1)

• Barth A, Hossain M, Brimhall DB, Perry CR, Tiffany CA, Xu S, Dumont EF. Pharmacokinetics of Oral Formulations of Gepotidacin (GSK2140944), a Triazaacenaphthylene Bacterial Type II Topoisomerase Inhibitor, in Healthy Adult and Adolescent Participants. Antimicrob Agents Chemother. 2022 Jan 18;66(1):e0126321. doi: 10.1128/AAC.01263-21. Epub 2021 Oct 11.

  PMID: 34633853 DERIVED

MeSH Terms

Conditions

Bacterial Infections

Interventions

gepotidacin

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a double-blind study.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 is a 3-period, fixed-sequence study of a single 1500-mg dose (Period 1) and two 3000-mg doses of gepotidacin at Hours 0 and 12 (Period 2) and Hours 0 and 6 (Period 3) in healthy adult subjects. Part 2 is a 2-period, fixed sequence study of a single 1500 mg dose (Period 1) of gepotidacin and two 3000 mg doses (Period 2) of gepotidacin in healthy adolescent subjects. .

Study Record Dates

• First Submitted: September 3, 2019
• First Posted: September 6, 2019
• Study Start: September 4, 2019
• Primary Completion: November 25, 2019
• Study Completion: November 25, 2019
• Last Updated: September 4, 2020
• Results First Posted: September 4, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (1)