Last updated: 11/17/2021 12:20:06

Pharmacokinetics of gepotidacin tablets in adults and adolescents subjects

GSK study ID
209611
See study documents
Clinicaltrials.gov ID
NCT04079790
See results summary
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A Phase I, Double-Blind, Two-Part, Sequential Study to Evaluate the Pharmacokinetics of Gepotidacin Tablets in Healthy Adult and Adolescent Participants
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Sequential Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

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

Timeframe: From Day 1 pre-dose up to Day 3

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

Timeframe: From Day 1 pre-dose up to Day 3

Part 1- Period 1: Area under the concentration-time curve from time 0 (pre-dose) to 24 hours postdose (AUC[0-24]) after single dose administration of gepotidacin 1500 mg (Blood)

Timeframe: From Day 1 pre-dose up to Day 2

Part 1- Period 1: Area under the concentration-time curve from time 0 (pre-dose) to 48 hours postdose (AUC[0-48]) after single dose administration of gepotidacin 1500 mg (Blood)

Timeframe: From Day 1 pre-dose up to Day 3

Part 1- Period 1: Maximum observed concentration (Cmax) after single dose administration of gepotidacin 1500 mg

Timeframe: From Day 1 pre-dose up to Day 3

Part 1- Period 2: AUC(0-t) after two doses administration of gepotidacin 3000 mg at 12 hour dosing interval

Timeframe: From Day 5 pre-dose up to Day 7

Part 1- Period 3: AUC(0-t) after two doses administration of gepotidacin 3000 mg at 6 hour dosing interval

Timeframe: From Day 9 pre-dose up to Day 11

Part 1- Period 2: Area under the concentration-time curve from time 0 (pre-dose) to time tau (AUC[0-tau]) after two doses administration of gepotidacin 3000 mg at 12 hour dosing interval (Blood)

Timeframe: Day 5

Part 1- Period 3: AUC(0-tau) after two doses administration of gepotidacin 3000 mg at 6 hour dosing interval (Blood)

Timeframe: Day 9

Part 1- Period 2: AUC(0-24) after two doses administration of gepotidacin 3000 mg at 12 hour dosing interval (Blood)

Timeframe: From Day 5 pre-dose up to Day 6

Part 1- Period 3: AUC(0-24) after two doses administration of gepotidacin 3000 mg at 6 hour dosing interval (Blood)

Timeframe: From Day 9 pre-dose up to Day 10

Part 1- Period 2: AUC(0-48) after two doses administration of gepotidacin 3000 mg at 12 hour dosing interval (Blood)

Timeframe: From Day 5 pre-dose up to Day 7

Part 1- Period 3: AUC(0-48) after two doses administration of gepotidacin 3000 mg at 6 hour dosing interval (Blood)

Timeframe: From Day 9 pre-dose up to Day 11

Part 1- Period 2: Accumulation ratio after two doses administration of gepotidacin 3000 mg at 12 hour dosing interval

Timeframe: From Day 5 pre-dose up to Day 7

Part 1- Period 3: Accumulation ratio after two doses administration of gepotidacin 3000 mg at 6 hour dosing interval

Timeframe: From Day 9 pre-dose up to Day 11

Part 1- Period 2: Cmax after two doses administration of gepotidacin 3000 mg at 12 hour dosing interval

Timeframe: From Day 5 pre-dose up to Day 7

Part 1- Period 3: Cmax after two doses administration of gepotidacin 3000 mg at 6 hour dosing interval

Timeframe: From Day 9 pre-dose up to Day 11

Part 2- Period 1: AUC(0-t) after single dose administration of gepotidacin 1500 mg

Timeframe: Day 1 pre-dose up to Day 3

Part 2- Period 1: AUC(0-infinity) after single dose administration of gepotidacin 1500 mg

Timeframe: Day 1 pre-dose up to Day 3

Part 2- Period 1: AUC(0-24) after single dose administration of gepotidacin 1500 mg (Blood)

Timeframe: Day 1 pre-dose up to Day 2

Part 2- Period 1: AUC(0-48) after single dose administration of gepotidacin 1500 mg (Blood)

Timeframe: Day 1 pre-dose up to Day 3

Part 2- Period 1: Cmax after single dose administration of gepotidacin 1500 mg

Timeframe: Day 1 pre-dose up to Day 3

Part 2- Period 2: AUC(0-t) after two doses administration of gepotidacin 3000 mg

Timeframe: Day 1 pre-dose up to Day 3

Part 2- Period 2: AUC(0-tau) after two doses administration of gepotidacin 3000 mg (Blood)

Timeframe: Day 1

Part 2- Period 2: AUC(0-24) after two doses administration of gepotidacin 3000 mg (Blood)

Timeframe: Day 1 pre-dose up to Day 2

Part 2- Period 2: AUC(0-48) after two doses administration of gepotidacin 3000 mg (Blood)

Timeframe: Day 1 pre-dose up to Day 3

Part 2- Period 2: Cmax after two doses administration of gepotidacin 3000 mg

Timeframe: Day 1 pre-dose up to Day 3

Part 1: Number of subjects with adverse events (AEs) and serious adverse events (SAEs)

Timeframe: Up to day 19

Part 2: Number of subjects with AEs and SAEs

Timeframe: Up to Day 21

Part 1: Number of subjects with abnormal hematology parameters

Timeframe: Up to Day 11

Part 2: Number of subjects with abnormal hematology parameters

Timeframe: Up to Day 13

Part 1: Number of subjects with abnormal clinical chemistry parameters

Timeframe: Up to Day 11

Part 2: Number of subjects with abnormal clinical chemistry parameters

Timeframe: Up to Day 13

Part 1: Number of subjects with abnormal urinalysis parameters

Timeframe: Up to Day 11

Part 2: Number of subjects with abnormal urinalysis parameters

Timeframe: Up to Day 13

Part 1: Number of subjects with abnormal systolic blood pressure (SBP) and diastolic blood pressure (DBP)

Timeframe: Up to Day 11

Part 2: Number of subjects with abnormal SBP and DBP

Timeframe: Up to Day 13

Part 1: Number of subjects with abnormal heart rate

Timeframe: Up to Day 11

Part 2: Number of subjects with abnormal heart rate

Timeframe: Up to Day 13

Part 1: Number of subjects with abnormal 12-lead electrocardiogram (ECG)

Timeframe: Up to Day 11

Part 2: Number of subjects with abnormal 12-lead ECG

Timeframe: Up to Day 13

Secondary outcomes:

Part 1- Period 1: Total unchanged drug (Ae total) after single dose administration of gepotidacin 1500 mg

Timeframe: Day 1 up to Day 3

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

Timeframe: Day 1 up to Day 3

Part 1- Period 1: AUC(0-24) after single dose administration of gepotidacin 1500 mg (Urine)

Timeframe: Day 1 up to Day 2

Part 1- Period 1: AUC(0-48) after single dose administration of gepotidacin 1500 mg (Urine)

Timeframe: Day 1 up to Day 3

Part 1- Period 1: Percentage of the given dose of drug excreted in urine (fe%) after single dose administration of gepotidacin 1500 mg

Timeframe: Day 1 up to Day 3

Part 1- Period 1: Renal clearance of drug (CLr) after single dose administration of gepotidacin 1500 mg

Timeframe: Day 1 up to Day 3

Part 1- Period 2: Ae total after two doses administration of gepotidacin 3000 mg at 12 hour dosing interval

Timeframe: Day 5 up to Day 7

Part 1- Period 3: Ae total after two doses administration of gepotidacin 3000 mg at 6 hour dosing interval

Timeframe: Day 9 up to Day 11

Part 1- Period 2: Ae(t1-t2) after two doses administration of gepotidacin 3000 mg at 12 hour dosing interval

Timeframe: Day 5 up to Day 7

Part 1- Period 3: Ae(t1-t2) after two doses administration of gepotidacin 3000 mg at 6 hour dosing interval

Timeframe: Day 9 up to Day 11

Part 1- Period 2: AUC(0-tau) after two doses administration of gepotidacin 3000 mg at 12 hour dosing interval (Urine)

Timeframe: Day 5

Part 1- Period 3: AUC(0-tau) after two doses administration of gepotidacin 3000 mg at 6 hour dosing interval (Urine)

Timeframe: Day 9

Part 1- Period 2: AUC(0-24) after two doses administration of gepotidacin 3000 mg at 12 hour dosing interval (Urine)

Timeframe: Day 5 up to Day 6

Part 1- Period 3: AUC(0-24) after two doses administration of gepotidacin 3000 mg at 6 hour dosing interval (Urine)

Timeframe: Day 9 up to Day 10

Part 1- Period 2: AUC(0-48) after two doses administration of gepotidacin 3000 mg at 12 hour dosing interval (Urine)

Timeframe: Day 5 up to Day 7

Part 1- Period 3: AUC(0-48) after two doses administration of gepotidacin 3000 mg at 6 hour dosing interval (Urine)

Timeframe: Day 9 up to Day 11

Part 1- Period 2: fe% after two doses administration of gepotidacin 3000 mg at 12 hour dosing interval

Timeframe: Day 5 up to Day 7

Part 1- Period 3: fe% after two doses administration of gepotidacin 3000 mg at 6 hour dosing interval

Timeframe: Day 9 up to Day 11

Part 1- Period 2: CLr after two doses administration of gepotidacin 3000 mg at 12 hour dosing interval

Timeframe: Day 5 up to Day 7

Part 1- Period 3: CLr after two doses administration of gepotidacin 3000 mg at 6 hour dosing interval

Timeframe: Day 9 up to Day 11

Part 2- Period 1: Ae total after single dose administration of gepotidacin 1500 mg

Timeframe: Day 1 up to Day 3

Part 2- Period 1: Ae(t1-t2) after single dose administration of gepotidacin 1500 mg

Timeframe: Day 1 up to Day 3

Part 2- Period 1: AUC(0-24) after single dose administration of gepotidacin 1500 mg (Urine)

Timeframe: Day 1 up to Day 2

Part 2- Period 1: AUC(0-48) after single dose administration of gepotidacin 1500 mg (Urine)

Timeframe: Day 1 up to Day 3

Part 2- Period 1: fe% after single dose administration of gepotidacin 1500 mg

Timeframe: Day 1 up to Day 3

Part 2- Period 1: CLr after single dose administration of gepotidacin 1500 mg

Timeframe: Day 1 up to Day 3

Part 2- Period 2: Ae total after two doses administration of gepotidacin 3000 mg

Timeframe: Day 1 up to Day 3

Part 2- Period 2: Ae(t1-t2) after two doses administration of gepotidacin 3000 mg

Timeframe: Day 1 up to Day 3

Part 2- Period 2: AUC(0-tau) after two doses administration of gepotidacin 3000 mg (Urine)

Timeframe: Day 1

Part 2- Period 2: AUC(0-24) after two doses administration of gepotidacin 3000 mg (Urine)

Timeframe: Day 1 up to Day 2

Part 2- Period 2: AUC(0-48) after two doses administration of gepotidacin 3000 mg (Urine)

Timeframe: Day 1 up to Day 3

Part 2- Period 2: fe% after two doses administration of gepotidacin 3000 mg

Timeframe: Day 1 up to Day 3

Part 2- Period 2: CLr after two doses administration of gepotidacin 3000 mg

Timeframe: Day 1 up to Day 3

Part 1- Period 1: Time to reach maximum observed plasma concentration (Tmax) after single dose administration of gepotidacin 1500 mg

Timeframe: Day 1 up to Day 3

Part 1- Period 1: Lag time before observation of drug concentrations in sampled matrix (tlag) after single dose administration of gepotidacin 1500 mg

Timeframe: Day 1 up to Day 3

Part 1- Period 1: Terminal phase half-life (t1/2) after single dose administration of gepotidacin 1500 mg

Timeframe: Day 1 up to Day 3

Part 1- Period 2: Tmax after two doses administration of gepotidacin 3000 mg at 12 hour dosing interval

Timeframe: Day 5 up to Day 7

Part 1- Period 3: Tmax after two doses administration of gepotidacin 3000 mg at 6 hour dosing interval

Timeframe: Day 9 up to Day 11

Part 1- Period 2: tlag after two doses administration of gepotidacin 3000 mg at 12 hour dosing interval

Timeframe: Day 5 up to Day 7

Part 1- Period 3: tlag after two doses administration of gepotidacin 3000 mg at 6 hour dosing interval

Timeframe: Day 9 up to Day 11

Part 1- Period 2: t1/2 after two doses administration of gepotidacin 3000 mg at 12 hour dosing interval

Timeframe: Day 5 up to Day 7

Part 1- Period 3: t1/2 after two doses administration of gepotidacin 3000 mg at 6 hour dosing interval

Timeframe: Day 9 up to Day 11

Part 2- Period 1: Tmax after single dose administration of gepotidacin 1500 mg

Timeframe: Day 1 up to Day 3

Part 2- Period 1: tlag after single dose administration of gepotidacin 1500 mg

Timeframe: Day 1 up to Day 3

Part 2- Period 1: t1/2 after single dose administration of gepotidacin 1500 mg

Timeframe: Day 1 up to Day 3

Part 2- Period 2: Tmax after two doses administration of gepotidacin 3000 mg

Timeframe: Day 1 up to Day 3

Part 2- Period 2: tlag after two doses administration of gepotidacin 3000 mg

Timeframe: Day 1 up to Day 3

Part 2- Period 2: t1/2 after two doses administration of gepotidacin 3000 mg

Timeframe: Day 1 up to Day 3

Interventions:
Drug: Gepotidacin
Drug: Placebo
Enrollment:
34
Observational study model:
Not applicable
Primary completion date:
2019-25-11
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
Medical condition
Infections, Bacterial
Product
gepotidacin
Collaborators
Not applicable
Study date(s)
August 2019 to November 2019
Type
Interventional
Phase
1

Participation criteria

Sex
Female & Male
Age
12 - 64 Years
Accepts healthy volunteers
Yes
  • Inclusion Criteria
  • Subjects in Part 1 must be >=18 to <=64 years of age inclusive, at the time of signing the informed consent.
Inclusion and exclusion criteria
Inclusion 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.

Trial location(s)

Location
Status
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Location
GSK Investigational Site
Las Vegas, Nevada, United States, 89113
Status
Study Complete
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Study documents

Protocol
Available language(s): English
Download document(s)
Statistical analysis plan
Available language(s): English
Download document(s)

If you wish to request for full study report, please contact - [email protected]

Results overview

Results posted on ClinicalTrials.gov

Recruitment status
Completed
Actual primary completion date
2019-25-11
Actual study completion date
2019-25-11

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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