Pharmacokinetics of Gepotidacin Tablets in Adults and Adolescents Subjects

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 1

Conditions: Infections, Bacterial

Treatments: Drug: Gepotidacin; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04079790

209611

Details and patient eligibility

About

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.

Enrollment: 34 patients

Sex: All

Ages: 12 to 64 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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34 participants in 4 patient groups, including a placebo group

Subjects receiving Gepotidacin in Part 1

Experimental group

Description:

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.

Treatment:

Drug: Gepotidacin

Subjects receiving Placebo in Part 1

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Subjects receiving Gepotidacin in Part 2

Experimental group

Description:

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.

Treatment:

Drug: Gepotidacin

Subjects receiving Placebo in Part 2

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo