A Relative Bioavailability and Food-Effect Study of the Fixed Dose Combination of GSK3640254 and Dolutegravir (DTG) in Healthy Participants

NCT04857892 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 213055
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

This is a two part study to compare the relative bioavailability (BA) of 2 fixed dose combinations (FDCs) of GSK3640254/DTG with GSK3640254 and DTG administered together as single agents (Part 1) and to assess the effect of food on the pharmacokinetic (PK) of the selected FDC of GSK3640254/DTG (Part 2).

Conditions

HIV Infections

Keywords

Dolutegravir; GSK3640254; Fixed Dose Combinations; Bioavailability

Outcome Measures

Primary Outcomes (12)

• Part 1: Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of GSK3640254

  Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of GSK3640254.

  Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period

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

  Blood samples were collected at indicated time points for PK analysis of GSK3640254.

  Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period

• Part 1: Maximum Observed Concentration (Cmax) of GSK3640254

  Blood samples were collected at indicated time points for PK analysis of GSK3640254.

  Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period

• Part 1: AUC(0-inf) of DTG

  Blood samples were collected at indicated time points for PK analysis of DTG.

  Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period

• Part 1: AUC(0-t) of DTG

  Blood samples were collected at indicated time points for PK analysis of DTG.

  Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period

• Part 1: Cmax of DTG

  Blood samples were collected at indicated time points for PK analysis of DTG.

  Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period

• Part 2: AUC(0-inf) of GSK3640254

  Blood samples were collected at indicated time points for PK analysis of GSK3640254.

  Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period

• Part 2: AUC(0-t) of GSK3640254

  Blood samples were collected at indicated time points for PK analysis of GSK3640254.

  Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period.

• Part 2: Cmax of GSK3640254

  Blood samples were collected at indicated time points for PK analysis of GSK3640254.

  Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period

• Part 2: AUC(0-inf) of DTG

  Blood samples were collected at indicated time points for PK analysis of DTG.

  Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period

• Part 2: AUC(0-t) of DTG

  Blood samples were collected at indicated time points for PK analysis of DTG.

  Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period

• Part 2: Cmax of DTG

  Blood samples were collected at indicated time points for PK analysis of DTG.

  Pre-dose, 30 minutes, 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96 hours post dose in each treatment period

Secondary Outcomes (92)

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

  Up to 17 days

• Part 2: Number of Participants With Non-SAEs and SAEs

  Up to 9 days

• Part 1: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets

  Baseline (Day -1) and Days 2, 5 and 7

• Part 2: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets

  Baseline (Day -1) and Days 2, 5 and 7

• Part 1: Absolute Values for Hematology Parameter: Hemoglobin

  Baseline (Day -1) and Days 2, 5 and 7

Study Arms (5)

Part 1 : Treatment sequence ABC

EXPERIMENTAL

Participants will receive a single oral dose of GSK3640254 25 milligrams (mg) (2 x tablets), GSK3640254 100 mg (1 x tablet) and DTG 50 mg (1 x tablet) administered together under moderate fat and calorie conditions (reference) (Treatment A) in Period 1, followed by a single oral dose of GSK3640254/DTG, 150 mg/50 mg (1 x monolayer tablet) FDC administered under moderate fat and calorie conditions (Treatment B) in Period 2. In Period 3, participants will receive a single oral dose of GSK3640254 / DTG, 150 mg/50 mg (1 x bilayer tablet) FDC administered under moderate fat and calorie conditions (Treatment C).

Drug: GSK3640254; Drug: DTG; Drug: GSK3640254/DTG

Part 1 : Treatment sequence BCA

EXPERIMENTAL

Participants will receive a single oral dose of GSK3640254/DTG, 150 mg/50 mg (1 x monolayer tablet) FDC administered under moderate fat and calorie conditions (Treatment B) in Period 1, followed by a single oral dose of GSK3640254 / DTG, 150 mg/50 mg (1 x bilayer tablet) FDC administered under moderate fat and calorie conditions (Treatment C) in Period 2. In Period 3 participants will receive a single oral dose of GSK3640254 25 mg (2 x tablets), GSK3640254 100 mg (1 x tablet) and DTG 50 mg (1 x tablet) administered together under moderate fat and calorie conditions (reference) (Treatment A).

Drug: GSK3640254; Drug: DTG; Drug: GSK3640254/DTG

Part 1 : Treatment sequence CAB

EXPERIMENTAL

Participants will receive a single oral dose of GSK3640254 / DTG, 150 mg/50 mg (1 x bilayer tablet) FDC administered under moderate fat and calorie conditions (Treatment C) in period 1, followed by a single oral dose of GSK3640254 25 mg (2 x tablets), GSK3640254 100 mg (1 x tablet) and DTG 50 mg (1 x tablet) administered together under moderate fat and calorie conditions (reference) (Treatment A) in Period 2. In Period 3 participants will receive a single oral dose of GSK3640254/DTG, 150 mg/50 mg (1 x monolayer tablet) FDC administered under moderate fat and calorie conditions (Treatment B).

Drug: GSK3640254; Drug: DTG; Drug: GSK3640254/DTG

Part 2 : Treatment sequence DE

EXPERIMENTAL

Participants will receive a single oral dose of selected FDC from Part 1 of GSK3640254/DTG, 150 mg/50 mg administered under high fat and calorie conditions (Treatment D) in Period 1 followed by a single oral dose of selected FDC from Part 1 of GSK3640254/DTG, 150 mg/50 mg administered under fasted conditions (Treatment E) in Period 2.

Drug: GSK3640254/DTG

Part 2 : Treatment sequence ED

EXPERIMENTAL

Participants will receive a single oral dose of selected FDC from Part 1 of GSK3640254/DTG, 150 mg/50 mg administered under fasted conditions (Treatment E) in Period 1 followed by a single oral dose of selected FDC from Part 1 of GSK3640254/DTG, 150 mg/50 mg administered under high fat and calorie conditions (Treatment D) in Period 2.

Drug: GSK3640254/DTG

Interventions

GSK3640254 DRUG

GSK3640254 will be administered via oral route.

Part 1 : Treatment sequence ABC; Part 1 : Treatment sequence BCA; Part 1 : Treatment sequence CAB

DTG DRUG

DTG will be administered via oral route.

Part 1 : Treatment sequence ABC; Part 1 : Treatment sequence BCA; Part 1 : Treatment sequence CAB

GSK3640254/DTG DRUG

GSK3640254/DTG will be administered via oral route.

Part 1 : Treatment sequence ABC; Part 1 : Treatment sequence BCA; Part 1 : Treatment sequence CAB; Part 2 : Treatment sequence DE; Part 2 : Treatment sequence ED

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be 18 to 65 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, laboratory tests, and cardiac monitoring (history and ECG).
• Participants capable of giving signed informed consent.

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 gastro intestinal anatomy or motility (for example \[e.g.\], gastroesophageal reflux disease, gastric ulcers, gastritis) or 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).
• Clinically significant illness, including viral syndromes within 3 weeks of dosing.
• Participant with known or suspected active Coronavirus disease (COVID)-19 infection or contact with an individual with known COVID-19, within 14 days of study enrollment.
• Current enrollment or past participation within the last 30 days before signing of consent in any other clinical study involving an investigational study intervention (including an investigational COVID vaccine) or any other type of medical research.
• Prior exposure to GSK3640254 or prior intolerance to DTG in this or another clinical study.
• 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, any degree of atrioventricular block, or conduction abnormality) which, in the opinion of the investigator or ViiV Healthcare (VH)/GlaxoSmithKline (GSK) medical monitor, will interfere with the safety for the individual participant.

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (1)

GSK Investigational Site

Austin, Texas, 78744, United States

Location

MeSH Terms

Conditions

HIV Infections

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

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: This is a 2-part crossover study.

Study Record Dates

• First Submitted: April 20, 2021
• First Posted: April 23, 2021
• Study Start: April 21, 2021
• Primary Completion: September 10, 2021
• Study Completion: September 10, 2021
• Last Updated: March 12, 2024
• Results First Posted: March 12, 2024

Record last verified: 2023-08

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, key secondary endpoints and safety data 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)