Last updated: 01/05/2023 05:01:36

Drug-drug interaction study of gepotidacin

GSK study ID
213678
See study documents
Clinicaltrials.gov ID
NCT04493931
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 Pharmacokinetic, multi-cohort study in Healthy Adult Subjects to Assess Gepotidacin as Victim and as Perpetrator of Drug-Drug Interactions via CYP450, Renal and Intestinal Transporters, and to Assess Gepotidacin Pharmacokinetics in Japanese Healthy Adults
Trial description: This study is a drug-drug interaction (DDI), pharmacokinetics (PK), safety and tolerability study in adult healthy participants, including Japanese cohort. This study is designed to assess co-administration of probe substrates with gepotidacin in study cohorts 1 to 3 and establishing PK and safety in Japanese participants in cohort 4. Food effect will also be evaluated in cohort 4.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

Cohort 1: Maximum observed concentration (Cmax) of gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 1: Time to reach maximum observed plasma concentration (Tmax) of gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 1: Terminal phase half-life (t1/2) of gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 1: Area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC [0-t]) of gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 1: AUC from time 0 (predose) extrapolated to infinite time (AUC[0-infinity]) of gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 2: Cmax of gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 2: Lag time before observation of drug concentrations (Tlag) of gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 2: Tmax of gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 2: AUC(0-t) of gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 2: AUC(0-infinity) of gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 3: Cmax of digoxin

Timeframe: Up to 96 hours post dose in each period

Cohort 3: Tlag of digoxin

Timeframe: Up to 96 hours post dose in each period

Cohort 3: Tmax of digoxin

Timeframe: Up to 96 hours post dose in each period

Cohort 3: AUC(0-t) of digoxin

Timeframe: Up to 96 hours post dose in each period

Cohort 3: AUC(0-infinity) of digoxin

Timeframe: Up to 96 hours post dose in each period

Cohort 3: Cmax of midazolam

Timeframe: Up to 48 hours post dose in each period

Cohort 3: Tlag of midazolam

Timeframe: Up to 48 hours post dose in each period

Cohort 3: Tmax of midazolam

Timeframe: Up to 48 hours post dose in each period

Cohort 3: AUC(0-t) of midazolam

Timeframe: Up to 48 hours post dose in each period

Cohort 3: AUC(0-infinity) of midazolam

Timeframe: Up to 48 hours post dose in each period

Cohort 4: Cmax of gepotidacin after a single 1500 mg dose

Timeframe: Up to 48 hours post dose in Period 1 and Period 2

Cohort 4: Tmax of gepotidacin after a single 1500 mg dose

Timeframe: Up to 48 hours post dose in Period 1 and Period 2

Cohort 4: AUC from time 0 (predose) to 24 hours post dose administration (AUC [0-24]) of gepotidacin after a single 1500 mg dose

Timeframe: Up to 24 hours post dose in Period 1 and Period 2

Cohort 4: AUC from time 0 (predose) to 48 hours post dose administration (AUC [0-48]) of gepotidacin after a single 1500 mg dose

Timeframe: Up to 48 hours post dose in Period 1 and Period 2

Cohort 4: AUC(0-t) of gepotidacin after a single 1500 mg dose

Timeframe: Up to 48 hours post dose in Period 1 and Period 2

Cohort 4: AUC(0-infinity) of gepotidacin after a single 1500 mg dose

Timeframe: Up to 48 hours post dose in Period 1 and Period 2

Cohort 4: Cmax of gepotidacin after the first dose of 3000 mg (morning dose)

Timeframe: Up to 60 hours post morning dose in Period 3

Cohort 4: Tmax of gepotidacin after the first dose of 3000 mg (morning dose)

Timeframe: Up to 60 hours post morning dose in Period 3

Cohort 4: AUC from time 0 (predose) to time tau (AUC[0-tau]) of gepotidacin after the first dose of 3000 mg (morning dose)

Timeframe: Up to 60 hours post morning dose in Period 3

Cohort 4: Cmax of gepotidacin after the second dose of 3000 mg (evening dose)

Timeframe: From start of evening dose up to 48 hours post evening dose in Period 3

Cohort 4: Tmax of gepotidacin after the second dose of 3000 mg gepotidacin (evening dose)

Timeframe: From start of evening dose up to 48 hours post evening dose in Period 3

Cohort 4: AUC(0-tau) of gepotidacin after the second dose of 3000 mg (evening dose)

Timeframe: From start of evening dose up to 48 hours post evening dose in Period 3

Cohort 4: Accumulation ratio for Cmax (RoCmax) of gepotidacin after the second dose of 3000 mg (evening dose)

Timeframe: From start of morning dose up to 48 hours post evening dose in Period 3

Cohort 4: Accumulation ratio for AUC (RoAUC) of gepotidacin after the second dose of 3000 mg (evening dose)

Timeframe: From start of morning dose up to 48 hours post evening dose in Period 3

Cohort 4: AUC(0-24) of gepotidacin using the full profile (morning + evening doses) following two 3000 mg doses

Timeframe: From start of morning dose up to 24 hours post morning dose (first dose) in Period 3

Cohort 4: AUC(0-48) of gepotidacin using the full profile (morning + evening doses) following two 3000 mg doses

Timeframe: From start of morning dose up to 48 hours post morning dose (first dose) in Period 3

Cohort 4: AUC(0-t) of gepotidacin using the full profile (morning + evening doses) following two 3000 mg doses

Timeframe: From start of morning dose up to 60 hours post morning dose in Period 3

Cohort 4: Number of participants with non-serious adverse events (non-SAEs)

Timeframe: Up to Day 16

Cohort 4: Number of participants with serious adverse events (SAEs)

Timeframe: Up to Day 16

Cohort 4: Number of participants with abnormal vital signs

Timeframe: Up to Day 16

Cohort 4: Number of participants with abnormal electrocardiogram (ECG) findings

Timeframe: Up to Day 16

Cohort 4: Number of participants with abnormal hematology parameters

Timeframe: Up to Day 16

Cohort 4: Number of participants with abnormal clinical chemistry parameters

Timeframe: Up to Day 16

Cohort 4: Number of participants with abnormal urinalysis findings

Timeframe: Up to Day 16

Cohort 4: Cmax of gepotidacin after a single 1500 mg dose under fed conditions

Timeframe: Up to 48 hours post dose in Period 1 and Period 2

Cohort 4: Tlag of gepotidacin after a single 1500 mg dose under fed conditions

Timeframe: Up to 48 hours post dose in Period 1 and Period 2

Cohort 4: Tmax of gepotidacin after a single 1500 mg dose under fed conditions

Timeframe: Up to 48 hours post dose in Period 1 and Period 2

Cohort 4: AUC(0-t) of gepotidacin after a single 1500 mg dose under fed conditions

Timeframe: Up to 48 hours post dose in Period 1 and Period 2

Cohort 4: AUC(0-infinity) of gepotidacin after a single 1500 mg dose under fed conditions

Timeframe: Up to 48 hours post dose in Period 1 and Period 2

Secondary outcomes:

Cohort 1: AUC(0-24) of gepotidacin

Timeframe: Up to 24 hours post dose in each period

Cohort 1: AUC(0-48) of gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 1: Tlag of a gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 1: Apparent volume of distribution (Vz/F) of gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 1: Apparent oral clearance (CL/F) of gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 1: Total unchanged drug (Ae total) of gepotidacin in urine

Timeframe: Up to 48 hours post dose in each period

Cohort 1: AUC(0-24) of gepotidacin in urine

Timeframe: Up to 24 hours post dose in each period

Cohort 1: AUC(0-48) of gepotidacin in urine

Timeframe: Up to 48 hours post dose in each period

Cohort 1: Renal clearance of drug (CLr) of gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 1: Amount of drug excreted in urine in a time interval (Ae[t1-t2]) of gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 1: Percentage of the given dose of drug excreted in urine (fe%) of gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 1: Number of participants with non-SAEs

Timeframe: Up to Day 14

Cohort 1: Number of participants with SAEs

Timeframe: Up to Day 14

Cohort 1: Number of participants with abnormal hematology parameters

Timeframe: Up to Day 14

Cohort 1: Number of participants with abnormal clinical chemistry parameters

Timeframe: Up to Day 14

Cohort 1: Number of participants with abnormal urinalysis findings

Timeframe: Up to Day 14

Cohort 1: Number of participants with abnormal vital signs

Timeframe: Up to Day 14

Cohort 1: Number of participants with abnormal ECG findings

Timeframe: Up to Day 14

Cohort 2: AUC(0-24) of gepotidacin

Timeframe: Up to 24 hours post dose in each period

Cohort 2: AUC(0-48) of gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 2: T1/2 of a gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 2: Vz/F of gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 2: CL/F of gepotidacin

Timeframe: Up to 48 hours post dose in each period

Cohort 2: Ae total of gepotidacin in urine

Timeframe: Up to 48 hours post dose in each period

Cohort 2: AUC(0-24) of gepotidacin in urine

Timeframe: Up to 24 hours post dose in each period

Cohort 2: AUC(0-48) of gepotidacin in urine

Timeframe: Up to 48 hours post dose in each period

Cohort 2: CLr of gepotidacin in urine

Timeframe: Up to 48 hours post dose in each period

Cohort 2: Ae(t1-t2) of gepotidacin in urine

Timeframe: Up to 48 hours post dose in each period

Cohort 2: fe% of gepotidacin in urine

Timeframe: Up to 48 hours post dose in each period

Cohort 2: Number of participants with non-SAEs

Timeframe: Up to Day 20

Cohort 2: Number of participants with SAEs

Timeframe: Up to Day 20

Cohort 2: Number of participants with abnormal hematology parameters

Timeframe: Up to Day 20

Cohort 2: Number of participants with abnormal clinical chemistry parameters

Timeframe: Up to Day 20

Cohort 2: Number of participants with abnormal urinalysis findings

Timeframe: Up to Day 20

Cohort 2: Number of participants with abnormal vital signs

Timeframe: Up to Day 20

Cohort 2: Number of participants with abnormal ECG findings

Timeframe: Up to Day 20

Cohort 3: Cmax of gepotidacin after the first dose of 3000 mg (morning dose)

Timeframe: Up to 60 hours post morning dose in each period

Cohort 3: Tmax of gepotidacin after the first dose of 3000 mg (morning dose)

Timeframe: Up to 60 hours post morning dose in each period

Cohort 3: Tlag of gepotidacin after the first dose of 3000 mg (morning dose)

Timeframe: Up to 60 hours post morning dose in each period

Cohort 3: AUC(0-tau) of gepotidacin first dose of 3000 mg (morning dose)

Timeframe: Up to 60 hours post morning dose in each period

Cohort 3: Cmax of gepotidacin after the second dose of 3000 mg (evening dose)

Timeframe: From start of evening dose up to 48 hours post evening dose in each Period

Cohort 3: Tmax of gepotidacin after the second dose of 3000 mg (evening dose)

Timeframe: From start of evening dose up to 48 hours post evening dose in each period

Cohort 3: RoCmax of gepotidacin after the second dose of 3000 mg (evening dose)

Timeframe: From start of morning dose up to 48 hours post evening dose in each period

Cohort 3: RoAUC of gepotidacin after the second dose of 3000 mg (evening dose)

Timeframe: From start of morning dose up to 48 hours post evening dose in each period

Cohort 3: AUC(0-tau) of gepotidacin after the second dose of 3000 mg (evening dose)

Timeframe: From start of evening dose up to 48 hours post evening dose in each period

Cohort 3: AUC(0-24) of gepotidacin using the full profile (morning + evening doses) following two 3000 mg doses

Timeframe: From start of morning dose up to 24 hours post morning dose in each period

Cohort 3: AUC(0-48) of gepotidacin using the full profile (morning + evening doses) following two 3000 mg doses

Timeframe: From start of morning dose up to 48 hours post morning dose in each period

Cohort 3: AUC(0-t) of gepotidacin using the full profile (morning + evening doses) following two 3000 mg doses

Timeframe: From start of morning dose up to 60 hours post morning dose in each period

Cohort 3: Vz/Fof gepotidacin using the full profile (morning + evening doses) following two 3000 mg doses

Timeframe: From start of morning dose up to 60 hours post morning dose in each period

Cohort 3: CL/F of gepotidacin using the full profile (morning + evening doses) following two 3000 mg doses

Timeframe: From start of morning dose up to 60 hours post morning dose in each period

Cohort 3: T1/2 of gepotidacin using the full profile (morning + evening doses) following two 3000 mg doses

Timeframe: From start of morning dose up to 60 hours post morning dose in each period

Cohort 3: Trough concentration (Cmin) of digoxin

Timeframe: Up to 96 hours post dose in each period

Cohort 3: t1/2 of digoxin

Timeframe: Up to 96 hours post dose in each period

Cohort 3: Vz/F of digoxin

Timeframe: Up to 96 hours post dose in each period

Cohort 3: CL/F of digoxin

Timeframe: Up to 96 hours post dose in each period

Cohort 3: Cmin of midazolam

Timeframe: Up to 48 hours post dose in each period

Cohort 3: t1/2 of midazolam

Timeframe: Up to 48 hours post dose in each period

Cohort 3: Vz/F of midazolam

Timeframe: Up to 48 hours post dose in each period

Cohort 3: CL/F of midazolam

Timeframe: Up to 48 hours post dose in each period

Cohort 3: Ae total of gepotidacin in urine following two 3000 mg doses

Timeframe: From start of morning dose up to 60 hours post morning dose in each period

Cohort 3: Ae(t1-t2) of gepotidacin in urine following two 3000 mg doses

Timeframe: From start of morning dose up to 60 hours post morning dose in each period

Cohort 3: AUC(0-tau) of gepotidacin in urine following two 3000 mg doses

Timeframe: From start of morning dose up to 60 hours post morning dose in each period

Cohort 3: AUC(0-24) of gepotidacin in urine following two 3000 mg doses

Timeframe: From start of morning dose up to 24 hours post morning dose in each period

Cohort 3: AUC(0-48) of gepotidacin in urine following two 3000 mg doses (urine)

Timeframe: From start of morning dose up to 48 hours post morning dose in each period

Cohort 3: fe% of gepotidacin in urine following two 3000 mg doses

Timeframe: From start of morning dose up to 48 hours post morning dose in each period

Cohort 3: CLr of gepotidacin in urine following two 3000 mg doses

Timeframe: From start of morning dose up to 60 hours post morning dose in each period

Cohort 3: Number of participants with non-SAEs

Timeframe: Up to Day 30

Cohort 3: Number of participants with SAEs

Timeframe: Up to Day 30

Cohort 3: Number of participants with abnormal hematology parameters

Timeframe: Up to Day 30

Cohort 3: Number of participants with abnormal clinical chemistry parameters

Timeframe: Up to Day 30

Cohort 3: Number of participants with abnormal urinalysis

Timeframe: Up to Day 30

Cohort 3: Number of participants with abnormal vital signs

Timeframe: Up to Day 30

Cohort 3: Number of participants with abnormal ECG findings

Timeframe: Up to Day 30

Cohort 4: T1/2 of gepotidacin after a single 1500 mg dose

Timeframe: Up to 48 hours post dose in Period 1 and Period 2

Cohort 4: Vz/F of gepotidacin after a single 1500 mg dose

Timeframe: Up to 48 hours post dose in Period 1 and Period 2

Cohort 4: CL/F of gepotidacin after a single 1500 mg dose

Timeframe: Up to 48 hours post dose in Period 1 and Period 2

Cohort 4: Tlag of gepotidacin after the first dose of 3000 mg (morning dose)

Timeframe: Up to 60 hours post morning dose in Period 3

Cohort 4: Vz/F of gepotidacin using the full profile (morning + evening doses) following two 3000 mg doses

Timeframe: From start of morning dose up to 60 hours post morning dose in Period 3

Cohort 4: CL/F of gepotidacin using the full profile (morning + evening doses) following two 3000 mg doses

Timeframe: From start of morning dose up to 60 hours post morning dose in Period 3

Cohort 4: t1/2 of gepotidacin using the full profile (morning + evening doses) following two 3000 mg doses

Timeframe: From start of morning dose up to 60 hours post morning dose in Period 3

Cohort 4: Ae total of gepotidacin in urine after a single 1500 mg dose

Timeframe: Up to 48 hours post dose in Period 1 and Period 2

Cohort 4: Ae(t1-t2) of gepotidacin in urine after a single 1500 mg dose

Timeframe: Up to 48 hours post dose in Period 1 and Period 2

Cohort 4: AUC(0-tau) of gepotidacin in urine after a single 1500 mg dose

Timeframe: Up to 48 hours post dose in Period 1 and Period 2

Cohort 4: AUC(0-24) of gepotidacin in urine after a single 1500 mg dose

Timeframe: Up to 24 hours post dose in Period 1 and Period 2

Cohort 4: AUC(0-48) of gepotidacin in urine after a single 1500 mg dose

Timeframe: Up to 48 hours post dose in Period 1 and Period 2

Cohort 4: fe% of gepotidacin in urine after a single 1500 mg dose

Timeframe: Up to 48 hours post dose in Period 1 and Period 2

Cohort 4: CLr of gepotidacin in urine after a single 1500 mg dose

Timeframe: Up to 48 hours post dose in Period 1 and Period 2

Cohort 4: Ae total of gepotidacin in urine following two 3000 mg doses

Timeframe: From start of morning dose up to 60 hours post morning dose in Period 3

Cohort 4: Ae(t1-t2) of gepotidacin in urine following two 3000 mg doses

Timeframe: From start of morning dose up to 60 hours post morning dose in Period 3

Cohort 4: AUC(0-tau) of gepotidacin in urine following two 3000 mg doses

Timeframe: From start of morning dose up to 60 hours post morning dose in Period 3

Cohort 4: AUC(0-24) of gepotidacin in urine following two 3000 mg doses

Timeframe: From start of morning dose up to 24 hours post morning dose in Period 3

Cohort 4: AUC(0-48) of gepotidacin in urine following two 3000 mg doses

Timeframe: From start of morning dose up to 48 hours post morning dose in Period 3

Cohort 4: fe% of gepotidacin in urine following two 3000 mg doses

Timeframe: From start of morning dose up to 60 hours post morning dose in Period 3

Cohort 4: CLr of gepotidacin in urine following two 3000 mg doses

Timeframe: From start of morning dose up to 60 hours post morning dose in Period 3

Interventions:
  • Drug: Gepotidacin
  • Drug: Cimetidine
  • Drug: Rifampicin
  • Drug: Midazolam
  • Drug: Digoxin
  • Other: Placebo matching to gepotidacin
    • Enrollment:
    64
    Primary completion date:
    2020-21-12
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    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
    Aline Barth, Caroline R. Perry, Shaila Shabbir, Maciej J. Zamek-Gliszczynski, Sebin Thomas, Etienne F. Dumont, Darin B. Brimhall, Dung Nguyen, Meenakshi Srinivasan, Brandon Swift. Clinical Assessment of Gepotidacin (GSK2140944) as a Victim and Perpetrator of Drug-Drug Interactions via CYP3A Metabolism and Transporters. Clin Transl Sci. 2023; DOI:10.1111/cts.13477 PMID: 36642822
    Medical condition
    Infections, Bacterial
    Product
    gepotidacin
    Collaborators
    Not applicable
    Study date(s)
    August 2020 to December 2020
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Female & Male
    Age
    18 - 50 Years
    Accepts healthy volunteers
    Yes
    • Participant must be greater than or equal to (>=) 18 to less than or equal to (=<) 50 years of age inclusive, at the time of signing the informed consent.
    • Participants 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. A participant 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.
    • Clinically significant abnormality in the past medical history or at the screening physical examination that in the investigator’s opinion may place the participant at risk or interfere with the outcome variables of the study. This includes, but is not limited to, history or current cardiac, hepatic, renal, neurologic, gastro-intestinal (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 participant at risk, in the opinion of the investigator.
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Participant must be greater than or equal to (>=) 18 to less than or equal to (=<) 50 years of age inclusive, at the time of signing the informed consent.
    • Participants 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. A participant 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.
    • Additional inclusion criteria for Japanese participants (Cohort 4): The participant is a non-naturalized Japanese citizen and holds a Japanese passport (current or expired). The participant has/had 2 Japanese parents and 4 Japanese grandparents who are/were all non-naturalized Japanese citizens, as confirmed by interview. The participant has been living outside of Japan for up to 10 years as confirmed by interview.
    • Participants have a body weight >=40 kilograms (kg) and body mass index within the range 18.5 to 32.0 kilograms per square meter (kg/m^2) (inclusive).
    • Male and/or female: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies: Is a woman of non-childbearing potential or Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of <1 percent (%), for at least 30 days prior to dosing until completion of the follow-up Visit. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated) in relationship to the first dose of study intervention. A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) before the first dose of study intervention and for women not on effective contraception at least 14 days prior to baseline visit. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
    • Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the 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 participant at risk or interfere with the outcome variables of the study. This includes, but is not limited to, history or current cardiac, hepatic, renal, neurologic, gastro-intestinal (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 participant at risk, in the opinion of the investigator.
    • Female participant has a positive pregnancy test result or is lactating at Screening or upon admission to the clinic.
    • Positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Note: Testing will be performed according to site procedures.
    • Within 2 months before Screening, either a confirmed history of Clostridium difficile (C. difficile) diarrhea infection or a past positive of C. 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/hypersensitivity to any of the study drugs, components thereof, or a history of drug or other allergy that, in the opinion of the Investigator or GlaxoSmithKline (GSK) Medical Monitor contraindicates their participation.
    • Cohort 2 Only: Participant is a contact lens wearer who is unable or unwilling to wear glasses for the duration of the study and for 5 half-lives after the last dose of rifampicin.
    • Use of any systemic antibiotic within 30 days of screening.
    • Participants must abstain from taking prescription or non-prescription drugs (except for hormonal contraceptives and/or acetaminophen at doses of <=2 grams/day), 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.
    • Participant has participated in a clinical trial and has received an investigational product (IP) prior to gepotidacin administration within 30 days, 5 half-lives, or twice the duration of the biological effect of IP (whichever is longer).
    • Past participation in this clinical study.
    • Baseline corrected QT interval using the Fridericia formula (QTcF) of >450 milliseconds (msec) at Screening or Check-in.
    • Presence of hepatitis B surface antigen or positive hepatitis C antibody test result at Screening or within 3 months prior to starting study intervention.
    • Alanine aminotransferase (ALT) >1.5 times upper limit of normal (ULN) at Screening or Check-in.
    • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at Screening or Check-in.
    • History of any kidney disease or current or chronic history of mild impaired renal function as indicated by an estimated creatinine clearance <=90 milliliters per minute (mL/min).
    • A positive test for human immunodeficiency virus (HIV) 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.
    • Cohort 3 Only: Digoxin-related exclusions include the following at Screening: Serum potassium >5.5 milliequivalent per liter (mEq/L) or < 3.6 mEq/L Serum magnesium <1.6 milligrams per deciliter (mg/dL) Serum calcium (total) <8.5 mg/dL History of hypersensitivity to digoxin or other digitalis glycosides Any clinically relevant abnormality on 12-lead ECG at Screening or Check-in.
    • Participant 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.
    • Participant is unable to comply with all study procedures, in the opinion of the investigator.
    • Participant should not participate in the study, in the opinion of the investigator or Sponsor.

    Trial location(s)

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

    Study documents

    Protocol
    Available language(s): English
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    Statistical analysis plan
    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
    2020-21-12
    Actual study completion date
    2020-21-12

    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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