A Randomized, Open-Label, Single-Dose, 2-Period, Crossover Study to Compare Gepotidacin Powder for Oral Suspension With the Adult Tablet Formulation in Healthy Male and Female Participants Aged 18 to 50 Years

GlaxoSmithKline1 site in 1 country24 target enrollmentMarch 1, 2022

ConditionsHealthy Volunteers

InterventionsGepotidacin

DrugsGepotidacin

Overview

Phase: Phase 1
Intervention: Gepotidacin
Conditions: Healthy Volunteers
Sponsor: GlaxoSmithKline
Enrollment: 24
Locations: 1
Primary Endpoint: Periods 1 and 2: Maximum observed plasma concentration (Cmax) of gepotidacin
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study is a randomized, open-label, two periods, cross-over pharmacokinetic, safety, tolerability and relative bioavailability of gepotidacin in healthy adult male and female participants of aged 18 to 50 years.

Registry

clinicaltrials.gov

Start Date

March 1, 2022

End Date

April 22, 2022

Last Updated

3 years ago

Study Type

Interventional

Study Design

Crossover

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Participant must be 18 to 50 years of age, inclusive, at the time of signing the informed consent.
•Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, clinical laboratory tests, vital sign measurements, and 12-lead electrocardiogram results. A participant with a clinical abnormality or laboratory parameters outside the reference range 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 more than or equal to (\>=) 50.0 kilograms (kg) (110 pound) for males and \>=45 kg (99 pound) for females and body mass index within the range 18.5 to 32.0 kilogram per square meters (kg/m\^2) (inclusive).
•Male 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. Male participants: Male participants are eligible to participate if they agree to the following during the study intervention period until completion of the follow-up visit: Refrain from donating sperm PLUS, either: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR Must agree to use contraception/barrier as detailed below: Agree to use a male condom with female partner and should also be advised of the benefit for a female partner to use a highly effective method of contraception, as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant. Agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person. b. Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies: Is not a WOCBP OR Is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of less than (\<) 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. 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 and in this protocol.

Exclusion Criteria

•History or presence of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs, constituting a risk when taking the study intervention, or interfering with the interpretation of data.
•Abnormal blood pressure as determined by the investigator or designee
•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.
•Positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at screening.
•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 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 the 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).

Arms & Interventions

Participants receiving gepotidacin powder for oral suspension followed by tablet

Intervention: Gepotidacin

Participants receiving gepotidacin tablet followed by powder for oral suspension

Intervention: Gepotidacin

Outcomes

Primary Outcomes

Periods 1 and 2: Maximum observed plasma concentration (Cmax) of gepotidacin

Time Frame: Up to 48 hours post dose in each period (each period is 3 days)

Blood samples will be collected for the concentrations of gepotidacin

Periods 1 and 2: Area under the concentration-time curve (AUC) from time zero (pre-dose) extrapolated to infinite time (AUC[0-infinity]) of gepotidacin

Time Frame: Up to 48 hours post dose in each period (each period is 3 days)

Blood samples will be collected for the concentrations of gepotidacin

Periods 1 and 2: AUC from time zero to the time of the last quantifiable concentration (AUC[0-t]) of gepotidacin

Time Frame: Up to 48 hours post dose in each period (each period is 3 days)

Blood samples will be collected for the concentrations of gepotidacin

Secondary Outcomes

Periods 1 and 2: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to 14 days)
Periods 1 and 2: Maximum change from Baseline in QT interval corrected with Fridericia's method (QTcF)(Baseline and up to 14 days)
Periods 1 and 2: Time to reach maximum observed plasma concentration (Tmax) of gepotidacin(Up to 48 hours post dose in each period (each period is 3 days))
Periods 1 and 2: Absorption lag time (Tlag) of gepotidacin(Up to 48 hours post dose in each period (each period is 3 days))
Periods 1 and 2: Terminal phase half-life (t1/2) of gepotidacin(Up to 48 hours post dose in each period (each period is 3 days))
Periods 1 and 2: Apparent volume of distribution (Vz/F) of gepotidacin(Up to 48 hours post dose in each period (each period is 3 days))
Periods 1 and 2: Relative bioavailability (Frel) of gepotidacin(Up to 48 hours post dose in each period (each period is 3 days))
Periods 1 and 2: Apparent oral clearance (CL/F) of gepotidacin(Up to 48 hours post dose in each period (each period is 3 days))
Periods 1 and 2: AUC from time zero to 24 hours (AUC[0-24]) of gepotidacin(Up to 24 hours post dose in each period (each period is 3 days))
Periods 1 and 2: Total unchanged drug (Ae total) of gepotidacin(Up to 48 hours post dose in each period (each period is 3 days))
Periods 1 and 2: Percentage of the given dose of drug excreted in urine (fe%) of gepotidacin(Up to 48 hours post dose in each period (each period is 3 days))
Periods 1 and 2: Renal clearance of drug (CLr) of gepotidacin(Up to 48 hours post dose in each period (each period is 3 days))