Clinical trial NCT04857892: A Relative Bioavailability and Food-Effect Study of the Fixed Dose Combination of GSK3640254 and Dolutegravir (DTG) in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Dolutegravir
GSK3640254
Fixed Dose Combinations
Bioavailability
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
First posted: 2021-04-23
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a 2-part crossover study.
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) of GSK3640254
timeFrame: 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
measure: Part 1: Area Under the Plasma Concentration-time Curve From Time 0 to Time t (AUC[0-t]) of GSK3640254
timeFrame: 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
measure: Part 1: Maximum Observed Concentration (Cmax) of GSK3640254
timeFrame: 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
measure: Part 1: AUC(0-inf) of DTG
timeFrame: 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
measure: Part 1: AUC(0-t) of DTG
timeFrame: 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
measure: Part 1: Cmax of DTG
timeFrame: 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
measure: Part 2: AUC(0-inf) of GSK3640254
timeFrame: 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
measure: Part 2: AUC(0-t) of GSK3640254
timeFrame: 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.
measure: Part 2: Cmax of GSK3640254
timeFrame: 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
measure: Part 2: AUC(0-inf) of DTG
timeFrame: 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
measure: Part 2: AUC(0-t) of DTG
timeFrame: 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
measure: Part 2: Cmax of DTG
timeFrame: 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:
measure: Part 1: Number of Participants With Non-Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 17 days
measure: Part 2: Number of Participants With Non-SAEs and SAEs
timeFrame: Up to 9 days
measure: Part 1: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 2: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Absolute Values for Hematology Parameter: Hemoglobin
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 2: Absolute Values for Hematology Parameter: Hemoglobin
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Absolute Values for Hematology Parameter: Erythrocytes
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 2: Absolute Values for Hematology Parameter: Erythrocytes
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Absolute Values for Hematology Parameters: Hematocrit
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 2: Absolute Values for Hematology Parameters: Hematocrit
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Absolute Values for Hematology Parameters: Erythrocytes Mean Corpuscular Hemoglobin
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 2: Absolute Values for Hematology Parameters: Erythrocytes Mean Corpuscular Hemoglobin
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Change From Baseline in Hematology Parameter: Hemoglobin
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 2: Change From Baseline in Hematology Parameter: Hemoglobin
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Change From Baseline in Hematology Parameter: Erythrocytes
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 2: Change From Baseline in Hematology Parameter: Erythrocytes
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Change From Baseline in Hematology Parameter: Hematocrit
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 2: Change From Baseline in Hematology Parameter: Hematocrit
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
timeFrame: Baseline (Day -1) and Days 2, 5, and 7
measure: Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Absolute Values for Clinical Chemistry Parameters: Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), Lactate Dehydrogenase (LDH), Creatinine Kinase (CK)
timeFrame: Baseline (Day -1), and Days 2, 5, and 7
measure: Part 2: Absolute Values of Clinical Chemistry Parameters: ALT, ALP, AST, GGT, LDH, CK
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Absolute Values of Clinical Chemistry Parameters: Calcium, Carbon-dioxide (CO2), Chloride, Glucose, Potassium, Sodium, Urea Nitrogen, Phosphorus, Triglycerides, Cholesterol, and Anion Gap
timeFrame: Baseline (Day -1), and Days 2, 5, and 7
measure: Part 2: Absolute Values of Clinical Chemistry Parameters: Calcium, CO2, Chloride, Glucose, Potassium, Sodium, Urea Nitrogen, Phosphorus, Triglycerides, Cholesterol, and Anion Gap
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Absolute Values for Chemistry Parameters: Serum Lipase, Serum Amylase
timeFrame: Baseline (Day -1), and Days 2, 5, and 7
measure: Part 2: Absolute Values for Chemistry Parameters: Serum Lipase, Serum Amylase
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Absolute Values of Clinical Chemistry Parameters: Albumin, Globulin and Protein
timeFrame: Baseline (Day -1), and Days 2, 5, and 7
measure: Part 2: Absolute Values of Clinical Chemistry Parameters: Albumin, Globulin and Protein
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Absolute Values of Clinical Chemistry Parameters: Creatinine, Direct Bilirubin, Bilirubin, and Urate
timeFrame: Baseline (Day -1), and Days 2, 5, and 7
measure: Part 2: Absolute Values of Clinical Chemistry Parameters: Creatinine, Direct Bilirubin, Bilirubin, and Urate
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Change From Baseline in Chemistry Parameters: ALT, ALP, AST, GGT, LDH, CK
timeFrame: Baseline (Day -1) and Days 2, 5, and 7
measure: Part 2: Change From Baseline in Chemistry Parameters: ALT, ALP, AST, GGT, LDH, CK
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Change From Baseline in Clinical Chemistry Parameters: Calcium, CO2, Chloride, Glucose, Potassium, Sodium, Urea Nitrogen, Phosphorus, Triglycerides, Cholesterol, and Anion Gap
timeFrame: Baseline (Day -1) and Days 2, 5, and 7
measure: Part 2: Change From Baseline in Clinical Chemistry Parameters: Calcium, CO2, Chloride, Glucose, Potassium, Sodium, Urea Nitrogen, Phosphorus, Triglycerides, Cholesterol, and Anion Gap
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Change From Baseline in Clinical Chemistry Parameters: Lipase and Amylase
timeFrame: Baseline (Day -1) and Days 2, 5, and 7
measure: Part 2: Change From Baseline in Clinical Chemistry Parameters: Lipase and Amylase
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Change From Baseline in Clinical Chemistry Parameters: Albumin, Globulin and Protein
timeFrame: Baseline (Day -1) and Days 2, 5, 7
measure: Part 2: Change From Baseline in Clinical Chemistry Parameters: Albumin, Globulin and Protein
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Change From Baseline in Clinical Chemistry Parameters: Creatinine, Direct Bilirubin, Bilirubin, and Urate
timeFrame: Baseline (Day -1) and Days 2, 5, and 7
measure: Part 2: Change From Baseline in Clinical Chemistry Parameters: Creatinine, Direct Bilirubin, Bilirubin, and Urate
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Absolute Values for Urinalysis Parameter: Specific Gravity
timeFrame: Baseline (Day -1) and Days 2, 5, and 7
measure: Part 2 : Absolute Values for Urinalysis Parameter: Specific Gravity
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Absolute Values for Urinalysis Parameters: Potential of Hydrogen (pH)
timeFrame: Baseline (Day -1) and Days 2, 5, and 7
measure: Part 1: Absolute Values for Urinalysis Parameter: Potential of Hydrogen
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Number of Participants With Urinalysis Dipstick Results: Glucose
timeFrame: Baseline (Day -1) and Days 2, 5, and 7
measure: Part 2: Number of Participants With Urinalysis Dipstick Results: Glucose
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Number of Participants With Urinalysis Dipstick Results: Protein
timeFrame: Baseline (Day -1) and Days 2, 5, and 7
measure: Part 2: Number of Participants With Urinalysis Dipstick Results: Protein
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Number of Participants With Urinalysis Dipstick Results: Occult Blood
timeFrame: Baseline (Day -1) and Days 2, 5, and 7
measure: Part 2: Number of Participants With Urinalysis Dipstick Results: Occult Blood
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Number of Participants With Urinalysis Dipstick Results: Ketones
timeFrame: Baseline (Day -1) and Days 2, 5, and 7
measure: Part 2: Number of Participants With Urinalysis Dipstick Results: Ketones
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Number of Participants With Urinalysis Dipstick Results: Bilirubin and Nitrite
timeFrame: Baseline (Day -1) and Days 2, 5, and 7
measure: Part 2: Number of Participants With Urinalysis Dipstick Results: Bilirubin and Nitrite
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Number of Participants With Urinalysis Dipstick Results: Leukocyte Esterase
timeFrame: Baseline (Day -1) and Days 2, 5, and 7
measure: Part 2: Number of Participants With Urinalysis Dipstick Results: Leukocyte Esterase
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Change From Baseline in Urinalysis Parameter: Specific Gravity
timeFrame: Baseline (Day -1) and Days 2, 5, and 7
measure: Part 2: Change From Baseline in Urinalysis Parameter: Specific Gravity
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Change From Baseline for Urinalysis Parameter: Potential of Hydrogen
timeFrame: Baseline (Day -1) and Days 2, 5, and 7
measure: Part 2: Change From Baseline for Urinalysis Parameter: Potential of Hydrogen
timeFrame: Baseline (Day -1) and Days 2, 5 and 7
measure: Part 1: Number of Participants With Worst Case Urine Parameter: Glucose Results by Maximum Grade Increase Post-Baseline Relative to Baseline
timeFrame: Up to Day 17
measure: Part 2: Number of Participants With Worst Case Urine Parameter: Glucose Results by Maximum Grade Increase Post-Baseline Relative to Baseline
timeFrame: Up to Day 9
measure: Part 1: Number of Participants With Worst Case Urine Parameter: Protein Results by Maximum Grade Increase Post-Baseline Relative to Baseline
timeFrame: Up to Day 17
measure: Part 2: Number of Participants With Worst Case Urine Parameter: Protein Results by Maximum Grade Increase Post-Baseline Relative to Baseline
timeFrame: Up to Day 9
measure: Part 1: Number of Participants With Worst Case Urine Parameter: Erythrocytes Results by Maximum Grade Increase Post-Baseline Relative to Baseline
timeFrame: Up to Day 17
measure: Part 2: Number of Participants With Worst Case Urine Parameter: Erythrocytes Results by Maximum Grade Increase Post-Baseline Relative to Baseline
timeFrame: Up to Day 9
measure: Part 1: Absolute Values of Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval and QT Interval Corrected by Fridericia's Formula (QTcF)
timeFrame: Baseline (Day 1, pre-dose), and Day 1: 2, 4, 6 hours, and Day 5
measure: Part 2: Absolute Values of ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF
timeFrame: Baseline (Day 1, pre-dose), and Day 1: 2, 4, 6 hours, and Days 5, 7
measure: Part 1: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF Interval
timeFrame: Baseline (Day 1, Pre-dose), and Day 1: 2, 4, 6 hours, and Day 5
measure: Part 2: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval and QTcF Interval
timeFrame: Baseline (Day 1, pre-dose), and Day 1: 2, 4, 6 hours, Days 5 and 7
measure: Part 1: Absolute Values of Vital Sign Parameters: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
timeFrame: Baseline (Day 1, pre-dose), and Day 1: 24, 48, 72 hours, Days 5 and 7
measure: Part 2: Absolute Values of Vital Signs: DBP and SBP
timeFrame: Baseline (Day 1, pre-dose), and Day 1: 24, 48 hours, Days 5 and 7
measure: Part 1: Absolute Values of Vital Signs: Pulse Rate
timeFrame: Baseline (Day 1, pre-dose), and Day 1: 24, 48, 72 hours, Days 5 and 7
measure: Part 2: Absolute Values of Vital Signs: Pulse Rate
timeFrame: Baseline (Day 1, pre-dose), and Day 1: 24, 48 hours, Day 5 and 7
measure: Part 1: Absolute Values of Vital Signs: Oral Temperature
timeFrame: Baseline (Day 1, pre-dose), and Day 1: 24, 48, 72 hours, Days 5, 6 and 7
measure: Part 2: Absolute Values of Vital Signs: Oral Temperature
timeFrame: Baseline (Day 1, pre-dose), and Day 1: 24, 48 hours, Day 5 and 7
measure: Part 1: Absolute Values of Vital Signs: Respiratory Rate
timeFrame: Baseline (Day 1, pre-dose), and Day 1: 24, 48, 72 hours, Days 5 and 7
measure: Part 2: Absolute Values of Vital Signs: Respiratory Rate
timeFrame: Baseline (Day 1, pre-dose), and Day 1: 24, 48 hours, Days 5, and 7
measure: Part 1: Change From Baseline in Vital Signs: DBP and SBP
timeFrame: Baseline (Day 1, pre-dose), and Day 1: 24, 48, 72 hours, Days 5, and 7
measure: Part 2: Change From Baseline in Vital Signs: DBP and SBP
timeFrame: Baseline (Day 1, pre-dose), and Day 1: 24, 48 hours, Days 5, and 7
measure: Part 1: Change From Baseline in Vital Signs: Pulse Rate
timeFrame: Baseline (Day 1, pre-dose), and Day 1: 24, 48, 72 hours, Days 5, and 7
measure: Part 2: Change From Baseline in Vital Signs: Pulse Rate
timeFrame: Baseline (Day 1, pre-dose), and Day 1: 24, 48 hours, Days 5, and 7
measure: Part 1: Change From Baseline in Vital Signs: Oral Temperature
timeFrame: Baseline (Day 1, pre-dose), and Day 1: 24, 48, 72 hours, Days 5, 6 and 7
measure: Part 2: Change From Baseline in Vital Signs: Oral Temperature
timeFrame: Baseline (Day 1, pre-dose), and Day 1: 24, 48 hours, Days 5, 6 and 7
measure: Part 1: Change From Baseline in Vital Signs: Respiratory Rate
timeFrame: Baseline (Day 1, pre-dose), and Day 1: 24, 48 hours, Days 5, and 7
measure: Part 2: Change From Baseline in Vital Signs: Respiratory Rate
timeFrame: Baseline (Day 1, pre-dose), and Day 1: 24, 48 hours, Days 5, and 7
Other outcomes:
Locations:
city: Austin
country: United States
facility: GSK Investigational Site
state: Texas
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: