A Relative Bioavailability and Food-Effect Study of GSK3640254 Tablet and Capsule Formulations in Healthy Participants

NCT ID: NCT04263142

Last Updated: 2021-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-27
• Study Completion Date: 2020-03-24

Brief Summary

This is an open-label, 2 part, single-dose and crossover study conducted to assess the relative bioavailability of a tablet compared to a capsule of GSK3640254 and to assess the effect of food on the GSK3640254 tablet in healthy participants. This study will also evaluate the effect of food (fasted, moderate fat meal, and high fat meal) on the pharmacokinetics of the GSK3640254 mesylate tablet formulation. In Part 1, participants will be randomly assigned to 1 of 2 treatment sequences (AB or BA) in two sequential treatment periods; and in Part 2, participants will be randomly assigned to 1 of 3 treatment sequences (CDE, DEC, or ECD) in three sequential treatment periods. Participants will be randomized to receive a single dose of GSK3640254 200 milligram (mg) capsules under moderate fat conditions and GSK3640254 200 mg tablets under moderate fat, fasted and high fat conditions in each treatment period. Approximately 30 participants will be enrolled.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Treatment AB

Participants will receive a single dose of GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in second intervention period. There will be at least 7 days wash out period between each dose of study intervention.

Group Type: EXPERIMENTAL

GSK3640254 Tablet

Intervention Type: DRUG

GSK3640254 tablets will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.

GSK3640254 Capsule

Intervention Type: DRUG

GSK3640254 capsules will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.

Part 1: Treatment BA

Participants will receive a single dose of GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in second intervention period. There will be at least 7 days wash out period between each dose of study intervention.

Group Type: EXPERIMENTAL

GSK3640254 Tablet

Intervention Type: DRUG

GSK3640254 tablets will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.

GSK3640254 Capsule

Intervention Type: DRUG

GSK3640254 capsules will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.

Part 2: Treatment CDE

Participants will receive a single dose of GSK3640254 200 mg (Treatment C- Test), tablets, orally under moderate fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment D- Reference), tablets, orally under fasted conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment E- Test), tablets, orally under high fat conditions on Day 1 in third intervention period. There will be at least 7 days wash out period between each dose of study intervention.

Group Type: EXPERIMENTAL

GSK3640254 Tablet

Intervention Type: DRUG

GSK3640254 tablets will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.

Part 2: Treatment DEC

Participants will receive a single dose of GSK3640254 200 mg (Treatment D- Reference), tablets, orally under fasted conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment E- Test), tablets, orally under high fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment C- Test), tablets, orally under moderate fat conditions on Day 1 in third intervention period. There will be at least 7 days wash out period between each dose of study intervention.

Group Type: EXPERIMENTAL

GSK3640254 Tablet

Intervention Type: DRUG

GSK3640254 tablets will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.

Part 2: Treatment ECD

Participants will receive a single dose of GSK3640254 200 mg (Treatment E- Test), tablets, orally under high fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment C- Test), tablets, orally under moderate fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment D- Reference), tablets, orally under fasted conditions on Day 1 in third intervention period. There will be at least 7 days wash out period between each dose of study intervention.

Group Type: EXPERIMENTAL

GSK3640254 Tablet

Intervention Type: DRUG

GSK3640254 tablets will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.

Interventions

GSK3640254 Tablet

GSK3640254 tablets will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.

Intervention Type: DRUG

GSK3640254 Capsule

GSK3640254 capsules will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participants must be 18 to 55 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 a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and ECG).
• Body weight >=50.0 kilogram (kg) (110 pounds [lbs]) for men and >=45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 31.0 kg per square meter (kg/m^2) (inclusive).
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants: Males shall not engage in intercourse while confined in the clinic. There is no need for an extended period of double barrier use or prolonged abstinence after study discharge. Female participants: 1. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: a. not a woman of childbearing potential (WOCBP); or Is a WOCBP and using a nonhormonal contraceptive method that is highly effective, with a failure rate of <1 percent (%), for 28 days before intervention, during the intervention period, and for at least 28 days after the last dose of study intervention. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. 2. A WOCBP must have a negative highly sensitive serum pregnancy test at Screening and Day -1. 3. Additional requirements for pregnancy testing during and after 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.

Exclusion Criteria

• Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• A pre-existing condition interfering with normal gastrointestinal (GI) anatomy or motility (example [e.g.], gastroesophageal reflux disease, gastric ulcers, gastritis), hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study intervention or render the participant unable to take oral study intervention.
• Prior cholecystectomy surgery (prior appendectomy is acceptable).
• Any history of significant underlying psychiatric disorder, including, but not limited to, schizophrenia, bipolar disorder with or without psychotic symptoms, other psychotic disorders, or schizotypal (personality) disorder.
• Any history of major depressive disorder with or without suicidal features, or anxiety disorders that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient treatment. Participants with other conditions such as adjustment disorder or dysthymia that have required shorter term medical therapy (<6 months) without inpatient treatment and are currently well-controlled clinically or resolved may be considered for entry after discussion and agreement with the Medical Monitor.
• Any pre-existing physical or other psychiatric condition (including alcohol or drug abuse), which, in the opinion of the investigator (with or without psychiatric evaluation), could interfere with the participant's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the participant.
• Medical history of cardiac arrhythmias, prior myocardial infarction in the past 3 months, or cardiac disease or a family or personal history of long QT syndrome.
• Presence of hepatitis B surface antigen at Screening or within 3 months prior to starting study intervention.
• Positive hepatitis C antibody test result at Screening or within 3 months prior to starting study intervention and positive on reflex to hepatitis C ribonucleic acid (RNA).
• Positive Human immunodeficiency virus (HIV)-1 and -2 antigen/antibody immunoassay at Screening.
• ALT >1.5 times upper limit of normal (ULN). A single repeat of ALT is allowed within a single Screening period to determine eligibility.
• Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). A single repeat of any laboratory abnormality is allowed within a single Screening period to determine eligibility.
• Any acute laboratory abnormality at Screening which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.
• Any Grade 2 to 4 laboratory abnormality at Screening, with the exception of creatine phosphokinase (CPK) and lipid abnormalities (e.g., total cholesterol, triglycerides), and ALT (described above), will exclude a participant from the study unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor. A single repeat of any laboratory abnormality is allowed within a single Screening period to determine eligibility.
• A positive test result for drugs of abuse (including marijuana), alcohol, or cotinine (indicating active current smoking) at Screening or before the first dose of study intervention.
• Unable to refrain from the use of prescription or nonprescription drugs including vitamins, herbal and dietary supplements (including Saint John's wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study intervention and for the duration of the study.
• Treatment with any vaccine within 30 days prior to receiving study intervention.
• Unwillingness to abstain from excessive consumption of any food or drink containing grapefruit and grapefruit juice, Seville oranges, blood oranges, or pomelos or their fruit juices within 7 days prior to the first dose of study intervention(s) until the end of the study.
• Participation in another concurrent clinical study or prior clinical study (with the exception of imaging trials) 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 study intervention (whichever is longer).
• Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within 56 days.
• Any positive (abnormal) response confirmed by the investigator on a screening clinician- or qualified designee-administered Columbia Suicide Severity Rating Scale (C-SSRS).
• Any significant arrhythmia or ECG finding (e.g., prior myocardial infarction in the past 3 months, symptomatic bradycardia, non-sustained or sustained atrial arrhythmias, non-sustained or sustained ventricular tachycardia, second-degree atrioventricular block Mobitz Type II, third-degree atrioventricular block, complete heart block, or conduction abnormality) which, in the opinion of the investigator or Medical Monitor, will interfere with the safety for the individual participant.
• History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 units. One unit is equivalent to 8 grams of alcohol: a half pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits.
• Unable to refrain from tobacco or nicotine-containing products within 3 months prior to 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

ViiV Healthcare

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

GSK Investigational Site

Austin, Texas, United States

Countries

United States

References

Johnson M, Pene Dumitrescu T, Joshi SR, Mathew A, Bainbridge V, Zhan J, Lataillade M. Relative Bioavailability and Food Effect of GSK3640254 Tablet and Capsule Formulations in Healthy Participants. Clin Pharmacol Drug Dev. 2022 May;11(5):632-639. doi: 10.1002/cpdd.1051. Epub 2022 Jan 7.

Reference Type: DERIVED

PMID: 34995417 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

213567

Identifier Type: -

Identifier Source: org_study_id