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

A Randomized, Open-Label, Single Dose, Four-Period Crossover Clinical Trial 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 is an open-label, single-dose, four-period, four sequential, and crossover study conducted to assess the relative bioavailability of GSK3640254 mesylate tablets and GSK3640254 mesylate capsules (in the presence of a moderate fat meal). This study will also evaluate the effect of food (fasted, moderate fat meal, and high fat meal) on the pharmacokinetics of GSK3640254 mesylate tablet formulation. 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 16 participants will be enrolled and the duration of the study will be approximately 54 days.

Study Overview

• Status: Terminated
• Conditions: HIV Infections
• Intervention / Treatment: Drug: GSK3640254 Tablet; Drug: GSK3640254 Capsule

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Participant 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 (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 or female: 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.
• 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.
• Positive Human immunodeficiency virus-1 and -2 antigen/antibody immunoassay at Screening.
• ALT >1.5 × upper limit of normal (ULN). A single repeat of ALT is allowed within a single Screening period to determine eligibility.
• Bilirubin >1.5 x ULN (isolated bilirubin >1.5 x 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 and lipid abnormalities (e.g., total cholesterol, triglycerides), and ALT, 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 non-prescription 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.
• Exclusion criteria for Screening ECG (a single repeat is allowed for eligibility determination): Heart rate: male <45 or >100 beats per minute (bpm) and female <50 or >100 bpm, and QTcF interval: male >450 millisecond (ms), female >450 ms.
• 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 (~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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1 - Treatment ABCD; 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; followed by GSK3640254 200 mg (Treatment C- Reference), tablets, orally under fasted conditions on Day 1 in third intervention period; further followed by GSK3640254 200 mg (Treatment D- Test), tablets, orally under high fat conditions on Day 1 in fourth intervention period. There will be at least 7 days wash out period between each dose of study intervention.	Drug: GSK3640254 Tablet; GSK3640254 tablets will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.; Drug: GSK3640254 Capsule; GSK3640254 capsules will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.
Experimental: Sequence 2 - Treatment BADC; 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; followed by GSK3640254 200 mg (Treatment D- Test), tablets, orally under high fat conditions on Day 1 in third intervention period; further followed by GSK3640254 200 mg (Treatment C- Reference), tablets, orally under fasted conditions on Day 1 in fourth intervention period. There will be at least 7 days wash out period between each dose of study intervention.	Drug: GSK3640254 Tablet; GSK3640254 tablets will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.; Drug: GSK3640254 Capsule; GSK3640254 capsules will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.
Experimental: Sequence 3 - Treatment CDAB; Participants will receive a single dose of GSK3640254 200 mg (Treatment C- Reference), tablets, orally under fasted conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment D- Test), tablets, orally under high fat conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in third intervention period; further followed by GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in first intervention period. There will be at least 7 days wash out period between each dose of study intervention.	Drug: GSK3640254 Tablet; GSK3640254 tablets will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.; Drug: GSK3640254 Capsule; GSK3640254 capsules will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.
Experimental: Sequence 4 - Treatment DCBA; Participants will receive a single dose of GSK3640254 200 mg (Treatment D- Test), tablets, orally under high fat conditions on Day 1 in first intervention period; followed by GSK3640254 200 mg (Treatment C- Reference), tablets, orally under fasted conditions on Day 1 in second intervention period; followed by GSK3640254 200 mg (Treatment B- Test), tablets, orally under moderate fat conditions on Day 1 in third intervention period; further followed by GSK3640254 200 mg (Treatment A- Reference), capsules, orally under moderate fat conditions on Day 1 in first intervention period. There will be at least 7 days wash out period between each dose of study intervention.	Drug: GSK3640254 Tablet; GSK3640254 tablets will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.; Drug: GSK3640254 Capsule; GSK3640254 capsules will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0-infinity]) for GSK3640254 200 mg Capsules and Tablets Under Fed Condition (Treatment A and B)	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis. PK Parameter Population included all participants who underwent plasma PK sampling and had evaluable PK parameters estimated.	Pre-dose and at 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-infinity) for GSK3640254 200 mg Tablets Under Fasted and High Fat Condition (Treatment C and D)	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose and at 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 to Time t (AUC[0-t]) for GSK3640254 200 mg Capsules and Tablets Under Fed Condition (Treatment A and B)	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose and at 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-t) for GSK3640254 200 mg Tablets Under Fasted and High Fat Condition (Treatment C and D)	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose and at 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 200 mg Capsules and Tablets Under Fed Condition (Treatment A and B)	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose and at 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 200 mg Tablets Under Fasted and High Fat Condition (Treatment C and D)	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose and at 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 Cmax (Tmax) for GSK3640254 200 mg Capsules Under Fed Condition (Treatment A)	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose and at 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 Cmax (Tmax) for GSK3640254 200 mg Tablets Under Fed, Fasted and High Fat Condition (Treatment B, C and D)	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose and at 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; and other important medical events which may require medical or surgical intervention. Safety Population consisted of all participants who received at least 1 dose of study medication.	Up to Day 14
Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count	Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelet count.	Day 2
Absolute Values for Hematology Parameter: Hemoglobin	Blood samples were collected to analyze the hematology parameter: hemoglobin.	Day 2
Absolute Values for Hematology Parameter: Hematocrit	Blood samples were collected to analyze the hematology parameter: hematocrit.	Day 2
Absolute Values for Hematology Parameter: Erythrocytes	Blood samples were collected to analyze the hematology parameter: erythrocytes.	Day 2
Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume	Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume.	Day 2
Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin	Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin.	Day 2
Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen	Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and blood urea nitrogen.	Day 2
Absolute Values for Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase	Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST and gamma-glutamyl transferase.	Day 2
Absolute Values for Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin	Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin.	Day 2
Absolute Values for Chemistry Parameters: Albumin, Globulin, Protein	Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein.	Day 2
Absolute Values for Chemistry Parameters: Amylase, Lipase	Blood samples were collected to analyze the chemistry parameters: amylase and lipase.	Day 2
Absolute Values for Urine Parameter: Specific Gravity	Urine samples were collected to analyze the urine parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine.	Day 2
Absolute Values for Urine Parameter: Urobilinogen	Urine samples were collected to analyze the urine parameter: urobilinogen.	Day 2
Absolute Values for Urine Parameter: Potential of Hydrogen (pH)	Urine samples were collected to analyze the urine parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0).	Day 2
Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF), Corrected QT Interval Using Bazett's Formula (QTcB)	Twelve-lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval, QTcF Interval and QTcB Interval. Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes.	Day 1: 2 hours and 4 hours
Absolute Values for Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	SBP and DBP were measured in the semi-recumbent position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without any distractions.	Days 2, 3, 4, and 5
Absolute Values for Pulse Rate	Pulse rate was measured in the semi-recumbent position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without any distractions.	Days 2, 3, 4, and 5
Absolute Values for Respiratory Rate	Respiratory rate was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions.	Days 2, 3, 4, and 5
Absolute Values for Body Temperature	Body temperature was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions.	Days 2, 3, 4, and 5
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet Count	Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and at Day 2
Change From Baseline in Hematology Parameter: Hemoglobin	Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and at Day 2
Change From Baseline in Hematology Parameter: Hematocrit	Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and at Day 2
Change From Baseline in Hematology Parameter: Erythrocytes	Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and at Day 2
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume	Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and at Day 2
Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin	Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and at Day 2
Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Anion Gap, Calcium, Carbon Dioxide, Chloride, Phosphate, Potassium, Sodium, Blood Urea Nitrogen	Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, anion gap, calcium, carbon dioxide, chloride, phosphate, potassium, sodium and blood urea nitrogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and at Day 2
Change From Baseline in Chemistry Parameters: Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST and gamma-glutamyl transferase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and at Day 2
Change From Baseline in Chemistry Parameters: Urate, Creatinine, Bilirubin, Direct Bilirubin	Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and at Day 2
Change From Baseline in Chemistry Parameters: Albumin, Globulin, Protein	Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and at Day 2
Change From Baseline in Chemistry Parameters: Amylase, Lipase	Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and at Day 2
Change From Baseline in Urinalysis Parameter: Specific Gravity	Urine samples were collected to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and at Day 2
Change From Baseline in Urinalysis Parameter: Urobilinogen	Urine samples were collected to analyze the urinalysis parameter: urobilinogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and at Day 2
Change From Baseline in Urinalysis Parameter: pH	Urine samples were collected to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, prior to the first dose of study drug administration. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day -1) and at Day 2
Change From Baseline in PR Interval, QRS Duration, QT Interval, QTcF, QTcB	Twelve-lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval, QTcF Interval and QTcB Interval. Twelve-lead ECGs were performed with the participant in a supine or semi-supine position after a rest of at least 10 minutes. Baseline was defined as the average of the triplicate pre-dose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day 1, Pre-dose), Day 1: 2 hours and 4 hours
Change From Baseline in SBP and DBP	SBP and DBP were measured in the semi-recumbent position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without any distractions. Baseline was defined as the average of the triplicate pre-dose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5
Change From Baseline in Pulse Rate	Pulse rate was measured in the semi-recumbent position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without any distractions. Baseline was defined as the average of the triplicate pre-dose assessments within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5
Change From Baseline in Respiratory Rate	Respiratory rate was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5
Change From Baseline in Body Temperature	Body temperature was measured in the semi-recumbent position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits, within each treatment. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.	Baseline (Day 1, Pre-dose), Days 2, 3, 4, and 5
Lag Time for Absorption (Tlag) for GSK3640254	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Apparent Terminal Phase Half-life (t1/2) for GSK3640254	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Apparent Oral Clearance (CL/F) for GSK3640254	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Apparent Volume of Distribution (Vz/F) for GSK3640254	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.	Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
Plasma Pharmacokinetic Concentration of GSK3640254	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK Concentration Population included all participants who underwent plasma PK sampling and had evaluable PK assay results.	Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72 and 96 hours post-dose

Collaborators and Investigators

• Sponsor: ViiV Healthcare

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2019
• Primary Completion (Actual): November 15, 2019
• Study Completion (Actual): November 15, 2019

Study Registration Dates

• First Submitted: October 1, 2019
• First Submitted That Met QC Criteria: October 14, 2019
• First Posted (Actual): October 16, 2019

Study Record Updates

• Last Update Posted (Actual): August 25, 2020
• Last Update Submitted That Met QC Criteria: August 7, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Safety; Healthy participants; Human immunodeficiency virus (HIV); GSK3640254
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: 209713

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: 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.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No