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

NCT04263142 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 213567
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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

Keywords

Healthy participants; GSK3640254; Human immunodeficiency virus; Relative Bioavailability

Outcome Measures

Primary Outcomes (8)

• Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0 to Inf]) for GSK3640254-Part 1

  Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis. PK parameters were calculated using standard non-compartmental analysis.

  pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

• Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Time t (AUC[0 to t]) for GSK3640254-Part 1

  Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.

  pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

• Maximum Observed Concentration (Cmax) for GSK3640254-Part 1

  Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.

  pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

• Time of Maximum Observed Concentration for GSK3640254-Part 1

  Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.

  pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

• AUC(0 to Inf) for GSK3640254-Part 2

  Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.

  pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

• AUC(0 to t) for GSK3640254-Part 2

  Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.

  pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

• Cmax for GSK3640254-Part 2

  Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.

  pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

• Time of Maximum Observed Concentration for GSK3640254-Part 2

  Blood samples were collected at indicated time points for PK analysis. PK parameters were calculated using standard non-compartmental analysis.

  pre-dose, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

Secondary Outcomes (90)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)-Part 1

  Up to Day 12

• Number of Participants With AEs and SAEs-Part 2

  Up to Day 19

• Absolute Values of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils and Platelets-Part 1

  Baseline (Day -1), Day 2 and Day 5

• Absolute Values for Erythrocytes Count-Part 1

  Baseline (Day -1), Day 2 and Day 5

• Absolute Values for Hemoglobin-Part 1

  Baseline (Day -1), Day 2 and Day 5

Study Arms (5)

Part 1: Treatment AB

EXPERIMENTAL

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.

Drug: GSK3640254 Tablet; Drug: GSK3640254 Capsule

Part 1: Treatment BA

EXPERIMENTAL

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.

Drug: GSK3640254 Tablet; Drug: GSK3640254 Capsule

Part 2: Treatment CDE

EXPERIMENTAL

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.

Drug: GSK3640254 Tablet

Part 2: Treatment DEC

EXPERIMENTAL

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.

Drug: GSK3640254 Tablet

Part 2: Treatment ECD

EXPERIMENTAL

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.

Drug: GSK3640254 Tablet

Interventions

GSK3640254 Tablet DRUG

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

Part 1: Treatment AB; Part 1: Treatment BA; Part 2: Treatment CDE; Part 2: Treatment DEC; Part 2: Treatment ECD

GSK3640254 Capsule DRUG

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

Part 1: Treatment AB; Part 1: Treatment BA

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions.

You may not qualify if:

• 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.

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (1)

GSK Investigational Site

Austin, Texas, 78744, United States

Location

Related Publications (1)

• 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.

  PMID: 34995417 DERIVED

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

GSK3640254

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: ViiV Healthcare

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This is an open label study.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Eligible participants will be randomly assigned to 1 of 2 treatment sequences (AB or BA) in Part 1 and 1 of 3 treatment sequences (CDE, DEC, or ECD) in Part 2.

Study Record Dates

• First Submitted: February 6, 2020
• First Posted: February 10, 2020
• Study Start: January 27, 2020
• Primary Completion: March 24, 2020
• Study Completion: March 24, 2020
• Last Updated: March 3, 2021
• Results First Posted: March 3, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (1)