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Pharmacokinetics of Gepotidacin Tablets in Adults and Adolescents Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04079790
Recruitment Status : Completed
First Posted : September 6, 2019
Results First Posted : September 4, 2020
Last Update Posted : September 4, 2020
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Infections, Bacterial Drug: Gepotidacin Drug: Placebo Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: 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. .
Masking: Double (Participant, Investigator)
Masking Description: This is a double-blind study.
Primary Purpose: Treatment
Official Title: A Phase I, Double-Blind, Two-Part, Sequential Study to Evaluate the Pharmacokinetics of Gepotidacin Tablets in Healthy Adult and Adolescent Participants
Actual Study Start Date : September 4, 2019
Actual Primary Completion Date : November 25, 2019
Actual Study Completion Date : November 25, 2019

Arm Intervention/treatment
Experimental: Subjects receiving Gepotidacin in Part 1
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
Tablets containing gepotidacin mesylate with a unit dose of 750 mg will be administered orally with 240 milliliter (mL) of water.

Placebo Comparator: Subjects receiving Placebo in Part 1
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
Tablets containing unit dose of placebo matching of gepotidacin will be administered orally with 240 mL of water.

Experimental: Subjects receiving Gepotidacin in Part 2
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
Tablets containing gepotidacin mesylate with a unit dose of 750 mg will be administered orally with 240 milliliter (mL) of water.

Placebo Comparator: Subjects receiving Placebo in Part 2
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
Tablets containing unit dose of placebo matching of gepotidacin will be administered orally with 240 mL of water.




Primary Outcome Measures :
  1. 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 [ Time Frame: 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.

  2. 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 [ Time Frame: 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.

  3. 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 [ Time Frame: 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.

  4. 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 [ Time Frame: 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.

  5. Part 1- Period 1: Maximum Observed Concentration (Cmax) After Single Dose Administration of Gepotidacin 1500 mg [ Time Frame: 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.

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

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

  8. 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 [ Time Frame: 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.

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

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

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

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

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

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

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

  16. Part 1- Period 3: RoCmax Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval [ Time Frame: 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.

  17. Part 1- Period 3: RoAUC Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval [ Time Frame: 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.

  18. Part 1- Period 2: Cmax Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval [ Time Frame: 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.

  19. Part 1- Period 3: Cmax Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval [ Time Frame: 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.

  20. Part 2- Period 1: AUC(0-t) After Single Dose Administration of Gepotidacin 1500 mg [ Time Frame: 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.

  21. Part 2- Period 1: AUC(0-infinity) After Single Dose Administration of Gepotidacin 1500 mg [ Time Frame: 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.

  22. Part 2- Period 1: AUC(0-24) After Single Dose Administration of Gepotidacin 1500 mg [ Time Frame: 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.

  23. Part 2- Period 1: AUC(0-48) After Single Dose Administration of Gepotidacin 1500 mg [ Time Frame: 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.

  24. Part 2- Period 1: Cmax After Single Dose Administration of Gepotidacin 1500 mg [ Time Frame: 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.

  25. Part 2- Period 2: AUC(0-t) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Interval [ Time Frame: 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.

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

  27. Part 2- Period 2: AUC(0-24) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Interval [ Time Frame: 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

  28. Part 2- Period 2: AUC(0-48) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Interval [ Time Frame: 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

  29. Part 2- Period 2: Cmax Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Interval [ Time Frame: 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.

  30. Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 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.

  31. Part 2: Number of Participants With Non-serious AEs and SAEs [ Time Frame: 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.

  32. Part 1: Number of Participants With Hematology Toxicities of Grade 3 or Higher [ Time Frame: 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.

  33. Part 2: Number of Participants With Hematology Toxicities of Grade 3 or Higher [ Time Frame: 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.

  34. Part 1: Number of Participants With Clinical Chemistry Toxicities of Grade 3 or Higher [ Time Frame: 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

  35. Part 2: Number of Participants With Clinical Chemistry Toxicities of Grade 3 or Higher [ Time Frame: 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

  36. Part 1: Number of Participants With Urinalysis Toxicities of Grade 3 or Higher [ Time Frame: 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

  37. Part 2: Number of Participants With Urinalysis Toxicities of Grade 3 or Higher [ Time Frame: 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

  38. Part 1: Number of Participants With Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Potential Clinical Importance [ Time Frame: 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).

  39. Part 2: Number of Participants With SBP and DBP of Potential Clinical Importance [ Time Frame: 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).

  40. Part 1: Number of Participants With Abnormal Heart Rate of Potential Clinical Importance [ Time Frame: 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).

  41. Part 2: Number of Participants With Abnormal Heart Rate of Potential Clinical Importance [ Time Frame: 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).

  42. Part 1: Period 1: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings [ Time Frame: 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.

  43. Part 1: Period 2: Number of Participants With Abnormal 12-lead ECG Findings [ Time Frame: 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.

  44. Part 1: Period 3: Number of Participants With Abnormal 12-lead ECG Findings [ Time Frame: 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.

  45. Part 2: Period 1: Number of Participants With Abnormal 12-lead ECG Findings [ Time Frame: 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.

  46. Part 2: Period 2: Number of Participants With Abnormal 12-lead ECG Findings [ Time Frame: 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 :
  1. Part 1- Period 1: Total Unchanged Drug (Ae Total) After Single Dose Administration of Gepotidacin 1500 mg [ Time Frame: 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.

  2. 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 [ Time Frame: 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.

  3. Part 1- Period 1: AUC(0-24) After Single Dose Administration of Gepotidacin 1500 mg (Urine) [ Time Frame: 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.

  4. Part 1- Period 1: AUC(0-48) After Single Dose Administration of Gepotidacin 1500 mg (Urine) [ Time Frame: 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.

  5. Part 1- Period 1: Percentage of the Given Dose of Drug Excreted in Urine (fe%) After Single Dose Administration of Gepotidacin 1500 mg [ Time Frame: 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 (%).

  6. Part 1- Period 1: Renal Clearance of Drug (CLr) After Single Dose Administration of Gepotidacin 1500 mg [ Time Frame: 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)

  7. Part 1- Period 2: Ae Total After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval [ Time Frame: 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.

  8. Part 1- Period 3: Ae Total After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval [ Time Frame: 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

  9. Part 1- Period 2: Ae(t1-t2) After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval [ Time Frame: 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

  10. Part 1- Period 3: Ae(t1-t2) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval [ Time Frame: 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.

  11. 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) [ Time Frame: 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.

  12. Part 1- Period 3: AUC(0-tau) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval (Urine) [ Time Frame: 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

  13. Part 1- Period 2: AUC(0-24) After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval (Urine) [ Time Frame: 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.

  14. Part 1- Period 3: AUC(0-24) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval (Urine) [ Time Frame: 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.

  15. Part 1- Period 2: AUC(0-48) After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval (Urine) [ Time Frame: 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

  16. Part 1- Period 3: AUC(0-48) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval (Urine) [ Time Frame: 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

  17. Part 1- Period 2: fe% After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval [ Time Frame: 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%.

  18. Part 1- Period 3: fe% After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval [ Time Frame: 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%.

  19. Part 1- Period 2: CLr After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval [ Time Frame: 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)

  20. Part 1- Period 3: CLr After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval [ Time Frame: 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)

  21. Part 2- Period 1: Ae Total After Single Dose Administration of Gepotidacin 1500 mg [ Time Frame: 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

  22. Part 2- Period 1: Ae(t1-t2) After Single Dose Administration of Gepotidacin 1500 mg [ Time Frame: 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.

  23. Part 2- Period 1: AUC(0-24) After Single Dose Administration of Gepotidacin 1500 mg (Urine) [ Time Frame: 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.

  24. Part 2- Period 1: AUC(0-48) After Single Dose Administration of Gepotidacin 1500 mg (Urine) [ Time Frame: 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.

  25. Part 2- Period 1: fe% After Single Dose Administration of Gepotidacin 1500 mg [ Time Frame: 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%.

  26. Part 2- Period 1: CLr After Single Dose Administration of Gepotidacin 1500 mg [ Time Frame: 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).

  27. Part 2- Period 2: Ae Total After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval [ Time Frame: 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.

  28. Part 2- Period 2: Ae(t1-t2) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval [ Time Frame: 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.

  29. 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) [ Time Frame: 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

  30. Part 2- Period 2: AUC(0-24) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval (Urine) [ Time Frame: 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.

  31. Part 2- Period 2: AUC(0-48) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval (Urine) [ Time Frame: 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

  32. Part 2- Period 2: fe% After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval [ Time Frame: 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%.

  33. Part 2- Period 2: CLr After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval [ Time Frame: 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).

  34. Part 1- Period 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) After Single Dose Administration of Gepotidacin 1500 mg [ Time Frame: 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.

  35. Part 1- Period 1: Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) After Single Dose Administration of Gepotidacin 1500 mg [ Time Frame: 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.

  36. Part 1- Period 1: Terminal Phase Half-life (t1/2) After Single Dose Administration of Gepotidacin 1500 mg [ Time Frame: 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.

  37. Part 1- Period 2: Tmax After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval [ Time Frame: 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.

  38. Part 1- Period 3: Tmax After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval [ Time Frame: 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.

  39. Part 1- Period 2: Tlag After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval [ Time Frame: 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.

  40. Part 1- Period 3: Tlag After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval [ Time Frame: 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.

  41. Part 1- Period 2: t1/2 After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval [ Time Frame: 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.

  42. Part 1- Period 3: t1/2 After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval [ Time Frame: 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.

  43. Part 2- Period 1: Tmax After Single Dose Administration of Gepotidacin 1500 mg [ Time Frame: 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.

  44. Part 2- Period 1: Tlag After Single Dose Administration of Gepotidacin 1500 mg [ Time Frame: 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.

  45. Part 2- Period 1: t1/2 After Single Dose Administration of Gepotidacin 1500 mg [ Time Frame: 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.

  46. Part 2- Period 2: Tmax After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval [ Time Frame: 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.

  47. Part 2- Period 2: Tlag After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval [ Time Frame: 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.

  48. Part 2- Period 2: t1/2 After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 64 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

  • 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.

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 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%).
  • History of any kidney disease or current or chronic history of impaired renal function as indicated by an estimated creatinine clearance <60 milliliter per minute (mL/min).
  • A positive test for human immunodeficiency virus antibody.
  • 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.
  • Urinary cotinine level indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 3 months before screening.
  • Clinically significant abnormal findings in serum chemistry, hematology, or urinalysis results obtained at screening or Day -1.
  • Baseline corrected QT interval using the Fridericia formula (QTcF) of >450 msec.
  • Subject 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.
  • Subject is unable to comply with all study procedures, in the opinion of the investigator.
  • Subject should not participate in the study, in the opinion of the investigator or sponsor.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04079790


Locations
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United States, Nevada
GSK Investigational Site
Las Vegas, Nevada, United States, 89113
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:
Study Protocol  [PDF] June 13, 2019
Statistical Analysis Plan  [PDF] December 10, 2019

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT04079790    
Other Study ID Numbers: 209611
First Posted: September 6, 2019    Key Record Dates
Results First Posted: September 4, 2020
Last Update Posted: September 4, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
GSK2140944
Gepotidacin
Pharmacokinetics
Healthy Adult
Healthy adolescent
Additional relevant MeSH terms:
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Bacterial Infections
Bacterial Infections and Mycoses
Infections