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

Study Overview
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Brief Summary
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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).

Official Title
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A Two-Part, Randomized, Open-Label, Single Dose, Crossover Clinical Study to Assess the Relative Bioavailability of Fixed-Dose Combinations of GSK3640254 and Dolutegravir and to Assess the Effect of Food on the Select Fixed Dose Combination of GSK3640254 and Dolutegravir in Healthy Participants

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: GSK3640254
* Drug: DTG
* Drug: GSK3640254/DTG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. 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 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is a 2-part crossover study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 : Treatment sequence ABC<br>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<br>* GSK3640254 will be administered via oral route.<br>Drug: DTG<br>* DTG will be administered via oral route.<br>Drug: GSK3640254/DTG<br>* GSK3640254/DTG will be administered via oral route.<br>|
| Experimental: Part 1 : Treatment sequence BCA<br>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<br>* GSK3640254 will be administered via oral route.<br>Drug: DTG<br>* DTG will be administered via oral route.<br>Drug: GSK3640254/DTG<br>* GSK3640254/DTG will be administered via oral route.<br>|
| Experimental: Part 1 : Treatment sequence CAB<br>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<br>* GSK3640254 will be administered via oral route.<br>Drug: DTG<br>* DTG will be administered via oral route.<br>Drug: GSK3640254/DTG<br>* GSK3640254/DTG will be administered via oral route.<br>|
| Experimental: Part 2 : Treatment sequence DE<br>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<br>* GSK3640254/DTG will be administered via oral route.<br>|
| Experimental: Part 2 : Treatment sequence ED<br>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<br>* GSK3640254/DTG will be administered via oral route.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts 1 and 2: Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC[0-inf]) for GSK3640254 and DTG |  | Up to Day 31 | 
| Parts 1 and 2: Area under the plasma concentration-time curve from time 0 to time t (AUC[0-t]) for GSK3640254 and DTG |  | Up to Day 31 | 
| Parts 1 and 2: Maximum observed concentration (Cmax) for GSK3640254 and DTG |  | Up to Day 31 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parts 1 and 2: Number of participants with adverse events (AEs) and Serious adverse events (SAEs) |  | Up to Day 31 | 
| Parts 1 and 2: Absolute values of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, absolute neutrophil count and platelet count (Giga cells per liter) |  | Up to Day 31 | 
| Parts 1 and 2: Absolute values of Hematology Parameter: Hemoglobin (Grams per Liter) |  | Up to Day 31 | 
| Parts 1 and 2: Absolute values of Hematology Parameter: Mean Corpuscular Volume (MCV) (Femtoliters) |  | Up to Day 31 | 
| Parts 1 and 2: Absolute values of Hematology Parameter: Red blood cell count (RBC) count (Trillion cells per liter) |  | Up to Day 31 | 
| Parts 1 and 2: Absolute values of Hematology Parameter: Hematocrit (Proportion of red blood cells in blood) |  | Up to Day 31 | 
| Parts 1 and 2: Absolute values of Hematology Parameter: Mean corpuscular hemoglobin (picograms) |  | Up to Day 31 | 
| Parts 1 and 2: Change from Baseline in hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Absolute neutrophil count and platelet count (Giga cells per liter) |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Change from Baseline in hematology Parameter: Hemoglobin (Grams per Liter) |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Change from Baseline in hematology Parameter: MCV (Femtoliters) |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Change from Baseline in hematology Parameter: RBC count (Trillion cells per liter) |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Change from Baseline in Hematology Parameter: Hematocrit (Proportion of red blood cells in blood) |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Change from Baseline in Hematology Parameter: Mean corpuscular hemoglobin (picograms) |  | Baseline and up to Day 31 | 
| Parts 1 and 2 Absolute values for Alanine Amino Transferase (ALT),Alkaline Phosphatase (ALP),Aspartate Amino Transferase (AST),Gamma Glutamyl Transferase (GGT),Lactate dehydrogenase, Creatinine phosphokinase(International units per Liter) |  | Up to Day 31 | 
| Parts 1 and 2: Absolute values of clinical chemistry parameters: Calcium, carbon-dioxide (CO2), chloride, glucose, potassium, sodium, Blood urea nitrogen, phosphorus, Triglycerides, total cholesterol, and Anion gap (Millimole per Liter) |  | Up to Day 31 | 
| Parts 1 and 2: Absolute values of clinical chemistry parameters: Serum lipase, serum amylase (Units per Liter) |  | Up to Day 31 | 
| Parts 1 and 2: Absolute values of clinical chemistry parameters: Albumin, Globulin and Total protein (grams per liter) |  | Up to Day 31 | 
| Parts 1 and 2: Absolute values of clinical chemistry parameters: Creatinine, direct bilirubin, total bilirubin, uric acid (micromoles per liter) |  | Up to Day 31 | 
| Parts 1 and 2: Change from Baseline in clinical chemistry parameters: ALT, ALP, AST, GGT, Lactate dehydrogenase, Creatinine phosphokinase (International units per Liter) |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Change from Baseline in clinical chemistry parameters: Calcium, CO2, chloride, glucose, potassium, sodium, Blood urea nitrogen, phosphorus, Triglycerides, total cholesterol, and Anion gap (Millimoles per Liter) |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Change from Baseline in clinical chemistry parameters: Serum lipase, serum amylase (Units per Liter) |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Change from Baseline in clinical chemistry parameters: Albumin, Globulin and Total protein (grams per liter) |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Change from Baseline in clinical chemistry parameters: Creatinine, direct bilirubin, total bilirubin, uric acid (micromoles per liter) |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Absolute values of Urinalysis parameter: Urine Specific Gravity |  | Up to Day 31 | 
| Parts 1 and 2: Absolute values of Urinalysis parameter: Urine potential of hydrogen (pH) |  | Up to Day 31 | 
| Parts 1 and 2: Absolute values of Urinalysis parameter: Glucose |  | Up to Day 31 | 
| Part 1 and 2: Absolute values of Urinalysis parameter: Protein |  | Up to Day 31 | 
| Part 1 and 2: Absolute values of Urinalysis parameter: Blood |  | Up to Day 31 | 
| Part 1 and 2: Absolute values of Urinalysis parameter: Ketones |  | Up to Day 31 | 
| Part 1 and 2: Absolute values of Urinalysis parameters: Bilirubin, Nitrite (Milligrams per deciliter) |  | Up to Day 31 | 
| Parts 1 and 2: Absolute values of Urinalysis parameter: Leukocyte esterase |  | Up to Day 31 | 
| Parts 1 and 2: Change from Baseline in Urinalysis parameter: Urine Specific Gravity |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Change from Baseline in Urinalysis parameter: Urine pH |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Change from Baseline in Urinalysis parameter: Glucose |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Change from Baseline in Urinalysis parameter: Protein |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Change from Baseline in Urinalysis parameter: Blood |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Change from Baseline in Urinalysis parameter: Ketones |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Change from Baseline in Urinalysis parameters: Bilirubin, Nitrite (Milligrams per deciliter) |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Change from Baseline in Urinalysis parameter: Leukocyte esterase |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Absolute values of Electrocardiogram (ECG) parameters: PR Interval, QRS Duration, QT Interval and QT Interval Corrected by Fridericia's Formula (QTcF) (milliseconds) |  | Up to Day 31 | 
| Parts 1 and 2: Change from Baseline in ECG parameters: PR Interval, QRS Duration, QT Interval and QTcF Interval (milliseconds) |  | Baseline and up to Day 31 | 
| Parts 1 and 2:Absolute values of vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) (millimeters of mercury) |  | Up to Day 31 | 
| Parts 1 and 2: Absolute values of vital signs: Pulse rate |  | Up to Day 31 | 
| Parts 1 and 2: Absolute values of vital signs: Temperature |  | Up to Day 31 | 
| Parts 1 and 2: Absolute values of vital signs : Respiratory rate |  | Up to Day 31 | 
| Parts 1 and 2: Change from Baseline in vital signs: DBP and SBP (millimeters of mercury) |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Change from Baseline in vital signs : Pulse rate |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Change from Baseline in vital signs: Temperature |  | Baseline and up to Day 31 | 
| Parts 1 and 2: Change from Baseline in vital signs: Respiratory rate |  | Baseline and up to Day 31 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bioavailability, Dolutegravir, GSK3640254, Fixed Dose Combinations