Last updated: 01/05/2023 04:50:11

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

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GSK study ID
117351
See study documents
Clinicaltrials.gov ID
NCT02853435
See results summary
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A Phase I; Multi-Center; Open-Label (Parts 1 and 2); Randomized, Double-Blind, Placebo-Controlled (Part 3); Single-Dose; 3-Part Study to Evaluate the Relative Bioavailability of Three Formulations in Healthy Subjects, Food Effect on Tablet Formulation in Healthy Subjects, and Pharmacokinetics of Gepotidacin (GSK2140944) in Japanese Subjects in Fasted and Fed States
Trial description: This study is divided in 2 parts. Part 1a is being conducted to evaluate the safety, tolerability, and relative bioavailability of the 2 free base tablet formulations (roller compacted [RC] and high shear wet granulation [HSWG]) compared to the reference capsule formulation under fasted conditions. This is a 3-period; cross-over study that will guide which gepotidacin formulation will be used for future studies. Following review of pharmacokinetic (PK) and safety data in Part 1a, a decision will be made whether to proceed with Parts 1b and 2.
Part 1b is a 2-period, cross-over study and will assess the effect of food on the PK of the selected gepotidacin tablet formulation from Part 1a. In Part 2, the PK of the selected gepotidacin tablet formulation from Part 1a in Japanese (2a) and Chinese (2b) subjects will be evaluated under fasted conditions.
The duration of the study (from Screening to the Follow-up visit) will be approximately 44 days (Part 1a), 41 days (Part 1b) and 38 days (Part 2a and 2b each), respectively. The approximate number of subjects enrolled in Part 1a will be 27 (9 subjects in each of the 3 treatment sequences), 16 in Part 1b (8 subjects in each of the 2 treatment sequences) and 12 Japanese and 12 Chinese subjects in Part 2a and 2b, respectively.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
None (Open Label)
Allocation:
Randomized
Primary outcomes:

Area under the concentration-time curve from time 0 (pre-dose) extrapolated to infinite time (AUC [0-infinity]) of plasma gepotidacin for Part 1a

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

Area under the concentration-time curve (AUC) from time 0 (pre-dose) to time of the last quantifiable concentration (AUC [0-t]) of plasma gepotidacin for Part 1a

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

Relative bioavailability of drug (Frel) of plasma gepotidacin for Part 1a

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

Maximum observed concentration (Cmax) determined directly from the concentration time data of plasma gepotidacin for Part 1a

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

Time to first occurrence of Cmax (tmax) of plasma gepotidacin for Part 1a

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

Lag time before observation of drug concentrations in sampled matrix (tlag) of plasma gepotidacin for Part 1a

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

Terminal phase half-life (t1/2) of plasma gepotidacin for Part 1a

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

Total unchanged drug (total amount of drug excreted in urine [Ae total]) for Part 1a

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

Percentage of the given dose of drug excreted in urine (fe%) of plasma gepotidacin for Part 1a

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

Renal clearance of drug in urine (CLr) for Part 1a

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

Amount of drug excreted in urine in a time intervals for pre-dose, 0 to 2 hours, 2 to 4 hours, 4 to 6 hours, 6 to 8 hours, 8 to 12 hours, 12 to 24 hours, 24 to 36 hours, and 36 to 48 hours (Ae [t1-t2]) for Part 1a

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

Area under the urine concentration-time curve over time 0 (pre-dose) to 12 hours (AUC [0-12]) for Part 1a

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

Area under the urine concentration-time curve over time 0 (pre-dose) to 24 hours (AUC [0-24]) after dosing for Part 1a

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

Area under the urine concentration-time curve over time 0 (pre-dose) to 48 hours (AUC [0-48]) after dosing for Part 1a

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

AUC (0-infinity) of plasma gepotidacin for Part 1b

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

AUC (0-t) of plasma gepotidacin for Part 1b

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

Cmax of plasma gepotidacin for Part 1b

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

tmax of plasma gepotidacin for Part 1b

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

tlag of plasma gepotidacin for Part 1b

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

t1/2 of plasma gepotidacin for Part 1b

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

AUC (0-infinity) of plasma gepotidacin for Part 2

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

AUC (0-t) of plasma gepotidacin for Part 2

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

Cmax of plasma gepotidacin for Part 2

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

tlag of plasma gepotidacin for Part 2

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

tmax of plasma gepotidacin for Part 2

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

t1/2 of plasma gepotidacin for Part 2

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

Total unchanged drug (Ae total) for Part 2

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

Ae (t1-t2) for Part 2

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

AUC (0-12) for Part 2

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

AUC (0-24) for Part 2

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

AUC (0-48) for Part 2

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

fe% for Part 2

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

CLr for Part 2

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

AUC (0-infinity) of plasma gepotidacin for Part 3

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

AUC (0-t) of plasma gepotidacin for Part 3

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

Cmax of plasma gepotidacin for Part 3

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

tmax of plasma gepotidacin for Part 3

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

tlag of plasma gepotidacin for Part 3

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

t1/2 of plasma gepotidacin for Part 3

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

Total unchanged drug (Ae total) for Part 3

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

Urine Ae (t1-t2) for Part 3

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

Urine AUC (0-12) for Part 3

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

Urine AUC (0-24) for Part 3

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

Urine AUC (0-48) for Part 3

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

fe% for Part 3

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

CLr for Part 3

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

Secondary outcomes:

Number of participants with non-serious adverse events (AEs) and serious adverse events (SAEs) for Part 1a

Timeframe: Up to 14 days

Change from Baseline in clinical chemistry parameters serum glucose, serum calcium, serum carbon dioxide, serum chloride, serum potassium, serum sodium and serum urea nitrogen for Part 1a

Timeframe: Baseline and up to 14 days

Change from Baseline in clinical chemistry parameters serum alanine aminotransferase (ALT), serum alkaline phosphatase (AP), serum aspartate aminotransferase (AST) and serum creatinine kinase (CK) for Part 1a

Timeframe: Baseline and up to 14 days

Change from Baseline in clinical chemistry parameters serum albumin and serum protein for Part 1a

Timeframe: Baseline and up to 14 days

Change from Baseline in clinical chemistry parameters serum bilirubin, serum creatinine and serum direct bilirubin for Part 1a

Timeframe: Baseline and up to 14 days

Change from Baseline in hematology parameters blood basophils, blood eosinophils, blood leukocytes, blood lymphocytes, blood monocytes, blood neutrophils and blood platelets for Part 1a

Timeframe: Baseline and up to 14 days

Change from Baseline in hematology parameters blood erythrocyte (Ery.) mean corpuscular hemoglobin concentration (MCHC) and blood hemoglobin for Part 1a

Timeframe: Baseline and up to 14 days

Change from Baseline in hematology parameter blood Ery. mean corpuscular hemoglobin (MCH) for Part 1a

Timeframe: Baseline and up to 14 days

Change from Baseline in hematology parameter blood Ery. mean corpuscular volume (MCV) for Part 1a

Timeframe: Baseline and up to 14 days

Change from Baseline in hematology parameter blood Ery. for Part 1a

Timeframe: Baseline and up to 14 days

Change from Baseline in hematology parameter blood hematocrit for Part 1a

Timeframe: Baseline and up to 14 days

Change from Baseline in vital sign parameters systolic blood pressure (SBP) and diastolic blood pressure (DBP) for Part 1a

Timeframe: Baseline and up to 14 days

Change from Baseline in vital sign parameter heart rate for Part 1a

Timeframe: Baseline and up to 14 days

Change from Baseline in electrocardiogram (ECG) parameter heart rate for Part 1a

Timeframe: Baseline and up to 14 days

Change from Baseline in ECG parameters PR interval, QRS duration, QT interval, corrected QT interval using Bazett’s formula (QTcB) and corrected QT interval using Fridericia’s formula (QTcF) for Part 1a

Timeframe: Baseline and up to 14 days

Number of participants with abnormal values on urinalysis by dipstick analysis Part 1a

Timeframe: Up to 14 days

Number of participants with AEs and SAEs for Part 1b

Timeframe: Up to 11 days

Change from Baseline in clinical chemistry parameters serum glucose, serum calcium, serum carbon dioxide, serum chloride, serum potassium, serum sodium and serum urea nitrogen for Part 1b

Timeframe: Baseline and up to 11 days

Change from Baseline in clinical chemistry parameters serum ALT, serum AP, serum AST and serum CK for Part 1b

Timeframe: Baseline and up to 11 days

Change from Baseline in clinical chemistry parameters serum albumin and serum protein for Part 1b

Timeframe: Baseline and up to 11 days

Change from Baseline in clinical chemistry parameters serum bilirubin, serum creatinine and serum direct bilirubin in Part 1b

Timeframe: Baseline and up to 11 days

Change from Baseline in hematology parameters blood basophils, blood eosinophils, blood leukocytes, blood lymphocytes, blood monocytes, blood neutrophils and blood platelets for Part 1b

Timeframe: Baseline and up to 11 days

Change from Baseline in hematology parameters blood Ery. MCHC and blood hemoglobin for Part 1b

Timeframe: Baseline and up to 11 days

Change from Baseline in hematology parameter blood Ery. MCH for Part 1b

Timeframe: Baseline and up to 11 days

Change from Baseline in hematology parameter blood Ery. MCV for Part 1b

Timeframe: Baseline and up to 11 days

Change from Baseline in hematology parameter blood Ery. for Part 1b

Timeframe: Baseline and up to 11 days

Change from Baseline in hematology parameter blood hematocrit for Part 1b

Timeframe: Baseline and up to 11 days

Change from Baseline in vital sign parameters SBP and DBP for Part 1b

Timeframe: Baseline and up to 11 days

Change from Baseline in vital sign parameter heart rate for Part 1b

Timeframe: Baseline and up to 11 days

Change from Baseline in ECG parameter heart rate for Part 1b

Timeframe: Baseline and up to 11 days

Change from Baseline in ECG parameters PR interval, QRS duration, QT interval, QTcB and QTcF for Part 1b

Timeframe: Baseline and up to 11 days

Number of participants with abnormal values on urinalysis by dipstick analysis Part 1b

Timeframe: Up to 11 days

Number of participants with non-serious AEs and SAEs for Part 2

Timeframe: Up to 11 days

Change from Baseline in clinical chemistry parameters serum glucose, serum calcium, serum carbon dioxide, serum chloride, serum potassium, serum sodium and serum urea nitrogen in Part 2

Timeframe: Baseline and up to 11 days

Change from Baseline in clinical chemistry parameters serum ALT, serum AP, serum AST and serum CK in Part 2

Timeframe: Baseline and up to 11 days

Change from Baseline in clinical chemistry parameters serum albumin and serum protein for Part 2

Timeframe: Baseline and up to 11 days

Change from Baseline in clinical chemistry parameters serum bilirubin, serum creatinine and serum direct bilirubin for Part 2

Timeframe: Baseline and up to 11 days

Change from Baseline in clinical chemistry parameter serum estradiol for Part 2

Timeframe: Baseline and up to 11 days

Change from Baseline in hematology parameters blood basophils, blood eosinophils, blood leukocytes, blood lymphocytes, blood monocytes, blood neutrophils and blood platelets for Part 2

Timeframe: Baseline and up to 11 days

Change from Baseline in hematology parameters Ery. MCHC and blood hemoglobin for Part 2

Timeframe: Baseline and up to 11 days

Change from Baseline in hematology parameter blood Ery. MCH for Part 2

Timeframe: Baseline and up to 11 days

Change from Baseline in hematology parameter blood Ery. MCV for Part 2

Timeframe: Baseline and up to 11 days

Change from Baseline in hematology parameter blood Ery. for Part 2

Timeframe: Baseline and up to 11 days

Change from Baseline in hematology parameter blood hematocrit for Part 2

Timeframe: Baseline and up to 11 days

Change from Baseline in vital sign parameters SBP and DBP for Part 2

Timeframe: Baseline and up to 11 days

Change from Baseline in vital sign parameter heart rate for Part 2

Timeframe: Baseline and up to 11 days

Change from Baseline in ECG parameter heart rate for Part 2

Timeframe: Baseline and up to 11 days

Change from Baseline in ECG parameters PR interval, QRS duration, QT interval, QTcB and QTcF for Part 2

Timeframe: Baseline and up to 11 days

Number of participants with abnormal values on urinalysis by dipstick analysis Part 2

Timeframe: Baseline and up to 11 days

Number of participants with non-serious AEs and SAEs for Part 3

Timeframe: Up to 14 days

Change from Baseline in clinical chemistry parameters serum glucose, serum calcium, serum carbon dioxide, serum chloride, serum potassium, serum sodium and serum urea nitrogen for Part 3

Timeframe: Baseline and up to 14 days

Change from Baseline in clinical chemistry parameters serum ALT, serum AP, serum AST and serum CK for Part 3

Timeframe: Baseline and up to 14 days

Change from Baseline in clinical chemistry parameters serum albumin and serum protein for Part 3

Timeframe: Baseline and up to 14 days

Change from Baseline in clinical chemistry parameters serum bilirubin and serum creatinine for Part 3

Timeframe: Baseline and up to 14 days

Change from Baseline in hematology parameters blood basophils, blood eosinophils, blood leukocytes, blood lymphocytes, blood monocytes, blood neutrophils and blood platelets for Part 3

Timeframe: Baseline and up to 14 days

Change from Baseline in hematology parameters blood Ery. MCHC and blood hemoglobin for Part 3

Timeframe: Baseline and up to 14 days

Change from Baseline in hematology parameter blood Ery. MCH for Part 3

Timeframe: Baseline and up to 14 days

Change from Baseline in hematology parameter blood Ery. mean corpuscular volume (MCV) for Part 3

Timeframe: Baseline and up to 14 days

Change from Baseline in hematology parameter blood Ery. for Part 3

Timeframe: Baseline and up to 14 days

Change from Baseline in hematology parameter blood hematocrit for Part 3

Timeframe: Baseline and up to 14 days

Change from Baseline in vital sign parameters SBP and DBP for Part 3

Timeframe: Baseline and up to 14 days

Change from Baseline in vital sign parameter heart rate for Part 3

Timeframe: Baseline and up to 14 days

Change from Baseline in ECG parameter heart rate for Part 3

Timeframe: Baseline and up to 14 days

Change from Baseline in ECG parameters PR interval, QRS duration, QT interval, QTcB and QTcF for Part 3

Timeframe: Baseline and up to 14 days

Number of participants with abnormal values on urinalysis by dipstick analysis Part 3

Timeframe: Up to 14 days

Interventions:
  • Drug: Gepotidacin RC Tablet
  • Drug: Gepotidacin HSWG Tablet
  • Drug: Gepotidacin Capsule
    • Enrollment:
    48
    Primary completion date:
    2017-17-10
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Aline Barth, Mohammad Hossain, Darin B. Brimhall, Caroline R. Perry, Courtney A. Tiffany, Sherry Xu, Etienne F. Dumont.Pharmacokinetics of Oral Formulations of Gepotidacin (GSK2140944), a Triazaacenaphthylene Bacterial Type II Topoisomerase Inhibitor, in Healthy Adult and Adolescent Participants.Antimicrob Agents Chemother.2021; DOI: 10.1128/AAC.01263-21 PMID: 34633853
    Aline Barth, Mohammad Hossain, Caroline R. Perry, Annette S. Gross, Hirofumi Ogura, Shaila Shabbir, Sebin Thomas, Etienne F. Dumont, Darin B. Brimhall, Meenakshi Srinivasan, Brandon Swift.Pharmacokinetic, Safety, and Tolerability Evaluations of Gepotidacin (GSK2140944) in Healthy Japanese Participants .Clin Pharmacol Drug Dev.2022; DOI: 10.1002/cpdd.1192
    Medical condition
    Infections, Bacterial
    Product
    gepotidacin
    Collaborators
    Not applicable
    Study date(s)
    August 2016 to October 2017
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Female & Male
    Age
    18 - 64 years
    Accepts healthy volunteers
    Yes
    • Inclusion Criteria
    • Male or female subjects between 18 and 64 years of age inclusive, at the time of signing the informed consent.
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Inclusion Criteria
    • Male or female subjects between 18 and 64 years of age inclusive, at the time of signing the informed consent.
    • Healthy as determined by the investigator based on medical history, clinical laboratory results (serum chemistry, hematology, urinalysis, and serology), vital sign measurements, 12-lead ECG results, and physical examination findings. A subject with a 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.
    • Additional inclusion criteria for Japanese subjects (Part 2a only): the subject was a non-naturalized Japanese citizen and held a Japanese passport, the subject had 2 Japanese parents and 4 Japanese grandparents who were all non naturalized Japanese citizens, as confirmed by interview and the subject had been living outside of Japan for up to 10 years as confirmed by interview.
    • Additional inclusion criteria for Chinese subjects (Part 2b only): the subject was a non-naturalized Chinese citizen and held a Chinese passport, the subject had 2 Chinese parents and 4 Chinese grandparents who were all non naturalized Chinese citizens, as confirmed by interview, the subject had been living outside of China for up to 10 years as confirmed by interview.
    • Body weight for subjects in Part 1a and 1b: more than equal to (>=) 50 kilogram (kg) and body mass index (BMI) within the range 19 and 32 kilogram per meter square (kg/m^2), inclusive and for Japanese and Chinese subjects (Part 2a and 2b): >=50 kg and BMI within the range 18 and 32 kg/m^2, inclusive.
    • Male or female: a female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin test, not lactating, and at least one of the following conditions applies. Non-reproductive potential defined as: pre-menopausal females with one of the following: documented tubal ligation, documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, hysterectomy, documented bilateral oophorectomy and postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle-stimulating hormone and estradiol levels consistent with menopause). Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. Reproductive potential and agrees to follow one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential from 30 days prior to the first dose of study medication and until completion of the Follow-up visit.
    • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol. Exclusion Criteria
    • Subject has a clinically significant abnormality in 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, respiratory, hematologic, or immunologic disease.
    • Subject has any surgical or medical condition (active or chronic) that may interfere with drug absorption, distribution, metabolism, or excretion of the study drug, or any other condition that may place the subject at risk, in the opinion of the investigator.
    • QTc more than (>) 450 millisecond (msec).
    • Use of a 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 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 sensitivity to heparin or heparin-induced thrombocytopenia (if the clinic uses heparin to maintain intravenous cannula patency).
    • Subjects cannot use any over-the-counter, or prescription medication (except for hormonal contraceptives and/or acetaminophen), vitamin supplement, or herbal medication within 7 days (or 5 half-lives, whichever is longer) before dosing and during the study.
    • 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 milliliter (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.
    • History of sensitivity to any of the study medications, or components thereof, or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
    • Presence of hepatitis B surface antigen, positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
    • Female subject has a positive pregnancy test result or is lactating at Screening or upon admission to the clinic.
    • 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 less than [<] 35 percent [%]).
    • Urinalysis positive for blood without other cause identified.
    • A positive pre-study drug/alcohol screen.
    • A positive test for human immunodeficiency virus antibody.
    • Subject has clinically significant abnormal findings in serum chemistry, hematology, or urinalysis results obtained at Screening or Day –1.
    • Donation of 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.
    • Previous exposure to gepotidacin within 12 months prior to the first dosing day.
    • Exclusion criteria for screening and baseline 12-lead ECG (a single repeat is allowed for eligibility determination): male subjects with heart rate <40 and >100 beats per minute (bpm), female subjects with heart rate <50 and >100 bpm, PR interval <120 and >220 msec for male and female subjects, QRS duration <70 and >120 msec in both male and female subjects and corrected QT interval using Bazett’s formula (QTcB) or corrected QT interval using Fridericia’s formula (QTcF) >450 msec in both male and female subjects. Evidence of previous myocardial infarction (does not include ST segment changes associated with repolarization). Any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular block [second degree or higher], Wolf Parkinson White syndrome), sinus pauses >3 seconds, non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats) or any significant arrhythmia which, in the opinion of the principal investigator and GlaxoSmithKline medical monitor, will interfere with the safety of the individual subject.
    • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
    • Subject is unable to comply with all study procedures, in the opinion of the investigator.
    • The subject should not participate in the study, in the opinion of the investigator or sponsor.

    Trial location(s)

    Location
    Status
    Contact us
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    Location
    GSK Investigational Site
    Anaheim, California, United States, 92801
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Austin, Texas, United States, 78744
    Status
    Study Complete
    Contact us

    Study documents

    Protocol
    Available language(s): English
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    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    Actual primary completion date
    2017-17-10
    Actual study completion date
    2017-17-10

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Additional information
    Not applicable
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