A Proof of Concept Study of GSK3640254 in Human Immunodeficiency Virus-1 (HIV-1) Infected Treatment-naive Adults

Sponsor

ViiV Healthcare (Industry)

Overall Status

Completed

CT.gov ID

NCT03784079

Collaborator

(none)

Enrollment

Locations

Arms

12.2

Actual Duration (Months)

1.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Infection with HIV-1 continues to be a serious health threat throughout the world. Chronic exposure to combination anti-retroviral therapy identified anti-retroviral associated long-term toxicities. Hence, there is a need to prevent these co-morbidities. GSK3640254 is a next-generation HIV-1 Maturation Inhibitor (MI) which may be effective for HIV-1 infection. This study will evaluate the antiviral effect, safety, tolerability and pharmacokinetics/ pharmacodynamics of GSK3640254 in HIV-1 infected treatment-naive adults. This study will consists of two parts; Part 1 and Part 2. Part 1 will evaluate two active doses of GSK3640254, 200 milligrams (mg) (Cohort 1) and 10 mg (Cohort 2) along with placebo to match GSK3640254 Mesylate salt. Part 2 will evaluate three active doses of GSK3640254. Dose level 1 of GSK3640254 that can provide at least 30 percent of the maximum effect (Cohort 1), dose level 2 of GSK3640254 that can provide at least 75 percent of the maximum effect (Cohort 2) and dose level 3 of GSK3640254 that can provide at least 90 percent of the maximum effect (Cohort 3). These doses are anticipated to be 5 mg, 40 mg and 100 mg respectively, but could be modified based on data obtained in Part 1. Subjects will also receive placebo to match GSK3640254 Mesylate salt in Part 2 of the study. All doses will be administered after a moderate fat meal. This study will consist of Screening period (up to 14 days), Treatment period (Day 1- Day 10), post-dose Follow-up (Day 11- Day 17) and final Follow-up (Day 18-24). A total of approximately 34 subjects will be enrolled, of which, 14 subjects will be randomized in Part 1 and 20 in Part 2 of the study. Six subjects will be enrolled in each of the active dose cohorts and 2 subjects will be enrolled in each of the placebo cohorts.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: GSK3640254 Drug: Placebo matching GSK3640254 Mesylate salt	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

Eligible subjects will be randomized to receive two active doses of GSK3640254 along with placebo in Part 1 of the study. In Part 2, subjects will receive three active doses of GSK3640254 along with placebo depending upon the data obtained in Part 1.Eligible subjects will be randomized to receive two active doses of GSK3640254 along with placebo in Part 1 of the study. In Part 2, subjects will receive three active doses of GSK3640254 along with placebo depending upon the data obtained in Part 1.

Masking:

Double (Participant, Investigator)

Masking Description:

This will be a double blind study. Subjects and investigator will be blinded.

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind (Sponsor-unblinded), Placebo-Controlled, Adaptive Trial to Investigate the Antiviral Effect, Safety, Tolerability and Pharmacokinetics of GSK3640254 in HIV-1 Infected Treatment-Naïve Adults

Actual Study Start Date :

Jan 31, 2019

Actual Primary Completion Date :

Feb 6, 2020

Actual Study Completion Date :

Feb 6, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: GSK3640254 10 mg Participants will receive GSK3640254 10 milligram (mg), capsules, orally for 10 days.	Drug: GSK3640254 GSK3640254 will be available with dosing strengths of 5 mg, 20 mg, and 100 mg to be administered as an oral capsule along with 240 mL of water.
Experimental: Part 1: GSK3640254 200 mg Participants will receive GSK3640254 200 mg, capsules, orally for 10 days.	Drug: GSK3640254 GSK3640254 will be available with dosing strengths of 5 mg, 20 mg, and 100 mg to be administered as an oral capsule along with 240 mL of water.
Placebo Comparator: Part 1: Placebo Participants will receive placebo capsules, orally for 10 days.	Drug: Placebo matching GSK3640254 Mesylate salt Placebo to match GSK3640254 Mesylate salt will be given as an oral capsule along with 240 mL of water
Experimental: Part 2: GSK3640254 40 mg Participants will receive GSK3640254 40 mg, capsules, orally for 7 days.	Drug: GSK3640254 GSK3640254 will be available with dosing strengths of 5 mg, 20 mg, and 100 mg to be administered as an oral capsule along with 240 mL of water.
Experimental: Part 2: GSK3640254 80 mg Participants will receive GSK3640254 80 mg, capsules, orally for 7 days.	Drug: GSK3640254 GSK3640254 will be available with dosing strengths of 5 mg, 20 mg, and 100 mg to be administered as an oral capsule along with 240 mL of water.
Experimental: Part 2: GSK3640254 140 mg Participants will receive GSK3640254 140 mg, capsules, orally for 7 days.	Drug: GSK3640254 GSK3640254 will be available with dosing strengths of 5 mg, 20 mg, and 100 mg to be administered as an oral capsule along with 240 mL of water.
Placebo Comparator: Part 2: Placebo Participants will receive placebo capsules, orally for 7 days.	Drug: Placebo matching GSK3640254 Mesylate salt Placebo to match GSK3640254 Mesylate salt will be given as an oral capsule along with 240 mL of water

Outcome Measures

Primary Outcome Measures

Part 1: Maximum Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Day 11 [Baseline (Day 1) and Day 11]
Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. A HIV-1 RNA polymerase chain reaction (PCR) assay with a lower limit of detection (LLOD) of 50 copies per milliliter was used. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Maximum Change From Baseline in Plasma HIV-1 RNA at Day 8 [Baseline (Day 1) and Day 8]
Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. An HIV-1 RNA PCR assay with an LLOD of 50 copies per milliliter was used. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Secondary Outcome Measures

Part 1: Number of Participants With Non-Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) [Up to Day 24]
An adverse event (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 or other situations as per Medical or scientific judgment. Safety Population consisted of all participants who were enrolled into the study with documented evidence of having received at least 1 dose of randomized treatment.
Part 2: Number of Participants With Non-SAEs and SAEs [Up to Day 12]
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 or other situations as per Medical or scientific judgment.
Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 1: Change From Baseline in Hematology Parameter: Hemoglobin [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 1: Change From Baseline in Hematology Parameter: Hematocrit [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 1: Change From Baseline in Hematology Parameter: Erythrocytes [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 1: Change From Baseline in Hematology Parameter: Reticulocytes/Erythrocyte [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: reticulocytes/erythrocyte (erythro). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count [Baseline (Day 1) and Visit 5 (Day 7)]
Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Change From Baseline in Hematology Parameter: Hemoglobin [Baseline (Day 1) and Visit 5 (Day 7)]
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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Change From Baseline in Hematology Parameter: Hematocrit [Baseline (Day 1) and Visit 5 (Day 7)]
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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Change From Baseline in Hematology Parameter: Erythrocytes [Baseline (Day 1) and Visit 5 (Day 7)]
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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume [Baseline (Day 1) and Visit 5 (Day 7)]
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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin [Baseline (Day 1) and Visit 5 (Day 7)]
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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Change From Baseline in Hematology Parameter: Reticulocytes/Erythro [Baseline (Day 1) and Visit 5 (Day 7)]
Blood samples were collected to analyze the hematology parameter: reticulocytes/erythro. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 1: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 1: Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST) [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 1: Change From Baseline in Chemistry Parameters: Creatinine, Bilirubin [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: creatinine and bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 1: Change From Baseline in Chemistry Parameters: Protein [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameter: protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 1: Change From Baseline in Chemistry Parameters: Amylase, Lipase [Baseline (Day 1) and Visit 6 (Day 11)]
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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol [Baseline (Day 1) and Visit 5 (Day 7)]
Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Change From Baseline in Chemistry Parameters: ALT, ALP, AST [Baseline (Day 1) and Visit 5 (Day 7)]
Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Change From Baseline in Chemistry Parameters: Creatinine, Bilirubin [Baseline (Day 1) and Visit 5 (Day 7)]
Blood samples were collected to analyze the chemistry parameters: creatinine and bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Change From Baseline in Chemistry Parameters: Protein [Baseline (Day 1) and Visit 5 (Day 7)]
Blood samples were collected to analyze the chemistry parameter: protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Change From Baseline in Chemistry Parameters: Amylase, Lipase [Baseline (Day 1) and Visit 5 (Day 7)]
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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 1: Change From Baseline in Urinalysis Parameter: Specific Gravity [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Urine samples were collected at Baseline and one sample between Days 8 to 10 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 1: Change From Baseline in Urinalysis Parameter: Urobilinogen [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Urine samples were collected at Baseline and one sample between Days 8 to 10 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 1: Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH) [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Urine samples were collected at Baseline and one sample between Days 8 to 10 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Change From Baseline in Urinalysis Parameter: Specific Gravity [Baseline (Day 1) and Visit 5 (Day 7)]
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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Change From Baseline in Urinalysis Parameter: Urobilinogen [Baseline (Day 1) and Visit 5 (Day 7)]
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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Change From Baseline in Urinalysis Parameter: pH [Baseline (Day 1) and Visit 5 (Day 7)]
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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
SBP and DBP were measured in the semi-supine position with a completely automated device 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 1: Change From Baseline in Respiratory Rate [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Respiratory rate was measured in the semi-supine position with a completely automated device 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 1: Change From Baseline in Pulse Rate [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Pulse rate was measured in the semi-supine position with a completely automated device 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Change From Baseline in SBP and DBP [Baseline (Day 1) and Visit 5 (Day 7)]
SBP and DBP were measured in the semi-supine position with a completely automated device 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Change From Baseline in Respiratory Rate [Baseline (Day 1) and Visit 5 (Day 7)]
Respiratory rate was measured in the semi-supine position with a completely automated device 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Change From Baseline in Pulse Rate [Baseline (Day 1) and Visit 5 (Day 7)]
Pulse rate was measured in the semi-supine position with a completely automated device 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 1: Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Bazett's Formula (QTcB), Corrected QT Interval Using Fridericia's Formula (QTcF) [Baseline (Day 1), Visit 5 (Days 8 to 10: Pre-dose, 2, 4 and 6 hours)]
Twelve lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval, QTcB Interval and QTcF Interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 2: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcB, QTcF [Baseline (Day 1), Visit 5 (Day 7: Pre-dose, 2, 4 and 6 hours)]
Twelve lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval, QTcB Interval and QTcF Interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Part 1: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Part 1: Absolute Values for Hematology Parameter: Hemoglobin [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 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.
Part 1: Absolute Values for Hematology Parameter: Hematocrit [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 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.
Part 1: Absolute Values for Hematology Parameter: Erythrocytes [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 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.
Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 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.
Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 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.
Part 1: Absolute Values for Hematology Parameter: Reticulocytes/Erythro [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: reticulocytes/erythro. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Part 2: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count [Baseline (Day 1) and Visit 5 (Day 7)]
Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Part 2: Absolute Values for Hematology Parameter: Hemoglobin [Baseline (Day 1) and Visit 5 (Day 7)]
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.
Part 2: Absolute Values for Hematology Parameter: Hematocrit [Baseline (Day 1) and Visit 5 (Day 7)]
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.
Part 2: Absolute Values for Hematology Parameter: Erythrocytes [Baseline (Day 1) and Visit 5 (Day 7)]
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.
Part 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume [Baseline (Day 1) and Visit 5 (Day 7)]
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.
Part 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin [Baseline (Day 1) and Visit 5 (Day 7)]
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.
Part 2: Absolute Values for Hematology Parameter: Reticulocytes/Erythro [Baseline (Day 1) and Visit 5 (Day 7)]
Blood samples were collected to analyze the hematology parameter: reticulocytes/erythro. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Part 1: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Part 1: Absolute Values for Chemistry Parameters: ALT, ALP, AST [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Part 1: Absolute Values for Chemistry Parameters: Creatinine, Bilirubin [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: creatinine and bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Part 1: Absolute Values for Chemistry Parameters: Protein [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameter: protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Part 1: Absolute Values for Chemistry Parameters: Amylase, Lipase [Baseline (Day 1) and Visit 6 (Day 11)]
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.
Part 2: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol [Baseline (Day 1) and Visit 5 (Day 7)]
Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Part 2: Absolute Values for Chemistry Parameters: ALT, ALP, AST [Baseline (Day 1) and Visit 5 (Day 7)]
Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Part 2: Absolute Values for Chemistry Parameters: Creatinine, Bilirubin [Baseline (Day 1) and Visit 5 (Day 7)]
Blood samples were collected to analyze the chemistry parameters: creatinine and bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Part 2: Absolute Values for Chemistry Parameters: Protein [Baseline (Day 1) and Visit 5 (Day 7)]
Blood samples were collected to analyze the chemistry parameter: protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Part 2: Absolute Values for Chemistry Parameters: Amylase, Lipase [Baseline (Day 1) and Visit 5 (Day 7)]
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.
Part 1: Absolute Values for Urinalysis Parameter: Specific Gravity [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Urine samples were collected at Baseline and one sample between Days 8 to 10 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.
Part 1: Absolute Values for Urinalysis Parameter: Urobilinogen [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Urine samples were collected at Baseline and one sample between Days 8 to 10 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.
Part 1: Absolute Values for Urinalysis Parameter: pH [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Urine samples were collected at Baseline and one sample between Days 8 to 10 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.
Part 2: Absolute Values for Urinalysis Parameter: Specific Gravity [Baseline (Day 1) and Visit 5 (Day 7)]
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.
Part 2: Absolute Values for Urinalysis Parameter: Urobilinogen [Baseline (Day 1) and Visit 5 (Day 7)]
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.
Part 2: Absolute Values for Urinalysis Parameter: pH [Baseline (Day 1) and Visit 5 (Day 7)]
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.
Part 1: Absolute Values for SBP and DBP [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
SBP and DBP were measured in the semi-supine position with a completely automated device 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.
Part 1: Absolute Values for Respiratory Rate [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Respiratory rate was measured in the semi-supine position with a completely automated device 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.
Part 1: Absolute Values for Pulse Rate [Baseline (Day 1) and Visit 5 (Days 8 to 10)]
Pulse rate was measured in the semi-supine position with a completely automated device 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.
Part 2: Absolute Values for SBP and DBP [Baseline (Day 1) and Visit 5 (Day 7)]
SBP and DBP were measured in the semi-supine position with a completely automated device 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.
Part 2: Absolute Values for Respiratory Rate [Baseline (Day 1) and Visit 5 (Day 7)]
Respiratory rate was measured in the semi-supine position with a completely automated device 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.
Part 2: Absolute Values for Pulse Rate [Baseline (Day 1) and Visit 5 (Day 7)]
Pulse rate was measured in the semi-supine position with a completely automated device 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.
Part 1: Absolute Values for ECG Parameters: PR, QRS, QT, QTcB and QTcF Intervals [Baseline (Day 1), Visit 5 (Days 8 to 10: Pre-dose, 2, 4 and 6 hours)]
Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, QTcF interval and QTcB interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Part 2: Absolute Values for ECG Parameters: PR, QRS, QT, QTcB and QTcF Intervals [Baseline (Day 1), Visit 5 (Day 7: Pre-dose, 2, 4 and 6 hours)]
Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, QTcF interval and QTcB interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Part 1: Area Under the Plasma Concentration Time Curve From Zero to 24 (AUC[0-24]) Following Administration of GSK3640254 on Day 1 [Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Pharmacokinetic (PK) Population consisted of all participants who received GSK3640254 and underwent plasma PK sampling during the study.
Part 1: Maximum Observed Concentration (Cmax) Following Administration of GSK3640254 on Day 1 [Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 1: Time to Maximum Observed Concentration (Tmax) Following Administration of GSK3640254 on Day 1 [Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 1: Concentration at 24 Hours Post-dose (C24) Following Administration of GSK3640254 on Day 1 [Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 1: Absorption Lag Time (Tlag) Following Administration of GSK3640254 on Day 1 [Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 2: AUC(0-24) Following Administration of GSK3640254 on Day 1 [Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 2: Cmax Following Administration of GSK3640254 on Day 1 [Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 2: Tmax Following Administration of GSK3640254 on Day 1 [Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 2: C24 Following Administration of GSK3640254 on Day 1 [Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 2: Tlag Following Administration of GSK3640254 on Day 1 [Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 1: Area Under the Plasma Drug Concentration-time Curve From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10 [Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 1: Cmax Following Repeat Dose Administration of GSK3640254 on Days 8 to 10 [Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 1: Tmax Following Repeat Dose Administration of GSK3640254 on Days 8 to 10 [Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 1: Pre-dose Concentration (C0) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10 [Days 8 to 10: Pre-dose]
Blood sample was collected at indicated time point for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 1: Concentration at End of Dosing Interval (Ctau) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10 [Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 1: Apparent Terminal Phase Half-life (t1/2) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10 [Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 1: Apparent Oral Clearance (CL/F) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10 [Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 2: AUC(0-tau) Following Repeat Dose Administration of GSK3640254 on Day 7 [Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 2: Cmax Following Repeat Dose Administration of GSK3640254 on Day 7 [Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 2: Tmax Following Repeat Dose Administration of GSK3640254 on Day 7 [Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 2: C0 Following Repeat Dose Administration of GSK3640254 on Day 7 [Day 7: Pre-dose]
Blood sample was collected at indicated time point for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 2: Ctau Following Repeat Dose Administration of GSK3640254 on Day 7 [Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 2: t1/2 Following Repeat Dose Administration of GSK3640254 on Day 7 [Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 2: CL/F Following Repeat Dose Administration of GSK3640254 on Day 7 [Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 AUC(0-tau) [Baseline (Day 1) and Day 8]
Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Statistical analysis for relationship between PK parameters (AUC) and PD measures (Change from Baseline in plasma HIV-1 RNA) were explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: maximum response (Emax), PK parameter value that attains 50 percent (%) of the maximal effect (EC50) and residual variability (s2e). PK/PD Population consisted of participants who met criteria for Per-Protocol and Pharmacokinetic Population analysis sets and who underwent PD sampling during the study.
Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 Cmax [Baseline (Day 1) and Day 8]
Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Statistical analysis for relationship between PK parameters (Cmax) and PD measures (Change from Baseline in plasma HIV-1 RNA) were explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: Emax, EC50 and s2e.
Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 Ctau [Baseline (Day 1) and Day 8]
Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Statistical analysis for relationship between PK parameters (Ctau) and PD measures (Change from Baseline in plasma HIV-1 RNA) were explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: Emax, EC50 and s2e.
Part 1: Accumulation Ratio Following Repeat Dose Administration of GSK3640254 [Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The accumulation ratios (Ro) were calculated as Ro_AUC equal to (=) AUC(0-tau) Days 8 to 10 divided by (/) AUC(0-24) Day 1; Ro_Cmax=Cmax Days 8 to 10/Cmax Day 1; and Ro_Ctau=Ctau Days 8 to 10/C24 Day 1.
Part 2: Accumulation Ratio Following Repeat Dose Administration of GSK3640254 [Days 1 and 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The accumulation ratios (Ro) were calculated as Ro_AUC=AUC(0-tau) Day 7/AUC(0-24) Day 1; Ro_Cmax=Cmax Day 7/Cmax Day 1; and Ro_Ctau=Ctau Day 7/C24 Day 1.
Part 1 and Part 2: Dose Proportionality of GSK3640254 Administered on Day 1 Based on AUC(0-24) [Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.
Part 1 and Part 2: Dose Proportionality of GSK3640254 Administered on Day 1 Based on Cmax [Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.
Part 1 and Part 2: Dose Proportionality of GSK3640254 Administered on Day 1 Based on C24 [Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.
Part 1 and Part 2: Dose Proportionality of GSK3640254 Following Repeat Dose Administration Based on AUC(0-tau) [Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.
Part 1 and Part 2: Dose Proportionality of GSK3640254 Following Repeat Dose Administration Based on Cmax [Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.
Part 1 and Part 2: Dose Proportionality of GSK3640254 Following Repeat Dose Administration Based on Ctau [Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
Subjects who are healthy (other than HIV infection) as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, laboratory tests, and cardiac monitoring.
Screening Cluster of designation 4 positive (CD4+) T-cell count >=350 cells per millimeter cube (cells/mm^3).
Documented HIV infection and Screening plasma HIV-1 RNA >=5000 copies/milliliter (mL). A single repeat of this test is allowed within a single Screening period to determine eligibility.
Treatment-naive: No anti-retrovirals (in combination or monotherapy) received after the diagnosis of HIV-1 infection.
Body weight >=50.0 kilograms (kg) (110 Pounds) for men and >=45.0 kg (99 pounds) for women and body mass index (BMI) within the range 18.5-31.0 kg/meter square (kg/m^2) (inclusive).
A female subject is eligible to participate if she is not pregnant, not breastfeeding, and not a woman of childbearing potential (WOCBP).
Capable of giving signed informed consent.
For subjects enrolled in France: a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria:

Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to starting study treatment.
Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study treatment and positive on reflex to Hepatitis C RNA.
ALT >2 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 percent).
Subjects with primary HIV infection, evidenced by acute retroviral syndrome (example given [e.g.], fever, malaise, fatigue, etc) and/or evidence of recent (within 3 months) documented viremia without antibody production and/or evidence of recent (within 3 months) documented seroconversion.
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 anatomy or motility (e.g., gastroesophageal reflux disease [GERD], gastric ulcers, gastritis), hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs or render the subject unable to take oral study treatment.
Any acute laboratory abnormality at screen which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.
Any Grade 2-4 laboratory abnormality at screen, with the exception of creatine phosphokinase (CPK) and lipid abnormalities (e.g., total cholesterol, triglycerides, etc), and ALT (described above), will exclude a subject 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 lab abnormality is allowed within a single screening period to determine eligibility.
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. Subjects 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 ViiV 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 subject's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the subject.
Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
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.
The subject has participated in a clinical trial and has received an investigational product within the 30 days prior to the first dosing day in the current study.
Any positive (abnormal) response confirmed by the investigator on a Screening clinician- (or qualified designee-) administered Columbia Suicide Severity Rating Scale (CSSRS).
Any positive result for illicit drug use (e.g., cocaine, heroin) at Screening. A positive screen for marijuana is not exclusionary, though if positive for delta-9-tetrahydrocannabinol (THC).
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.
Exposure to more than four new investigational drugs or vaccines within 12 months prior to the first dosing day.
Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 30 days of study drug administration or anticipated need for such treatment within the study.
Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia; or other localized malignancies require agreement between the investigator and the study medical monitor for inclusion of the subject prior to randomization.
Treatment with immunomodulating agents (such as systemic corticosteroids, interleukins, interferons) or any agent with known anti-HIV activity (such as hydroxyurea or foscarnet) within 30 days of study drug administration.
An active Center for Disease Control and Prevention (CDC) Category C disease except cutaneous Kaposi's sarcoma not requiring systemic therapy during the trial.
Treatment with any vaccine within 30 days prior to receiving study medication.
Exclusion criteria for screening electrocardiogram (a single repeat is allowed for eligibility determination): Heart rate of <45 or >100 beats per minute (bpm) for males and <50 or >100 bpm for females; PR Interval of <120 or >200 milliseconds (msec) for both males and females; QRS duration of <70 or >110 msec for both males and females; QT interval corrected (QTc) for heart rate according to Fridericia's formula (QTcF) of

450 msec for males and >470 msec for females. A heart rate from 100 to 110 bpm can be rechecked by electrocardiogram or vitals within 30 minutes to verify eligibility. QTcF is either machine read or manually over-read.

Any significant arrhythmia or electrocardiogram finding (e.g., prior myocardial infarction, sinoatrial pauses, bundle branch block, or conduction abnormality) which, in the opinion of the Investigator OR ViiV Medical Monitor, will interfere with the safety for the individual subject.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Bakersfield	California	United States	93301
2	GSK Investigational Site	Orlando	Florida	United States	32803
3	GSK Investigational Site	Marseille		France	13003
4	GSK Investigational Site	Paris		France	75018
5	GSK Investigational Site	Tourcoing cedex		France	59208
6	GSK Investigational Site	Muenchen	Bayern	Germany	81675
7	GSK Investigational Site	Frankfurt am Main	Hessen	Germany	60590
8	GSK Investigational Site	Roma	Lazio	Italy	00149
9	GSK Investigational Site	Milano	Lombardia	Italy	20127
10	GSK Investigational Site	Milano	Lombardia	Italy	20157
11	GSK Investigational Site	Johannesburg	Gauteng	South Africa	2113
12	GSK Investigational Site	Bloemfontein		South Africa	9301
13	GSK Investigational Site	Durban		South Africa	4001
14	GSK Investigational Site	Alicante		Spain	03010
15	GSK Investigational Site	Badalona		Spain	08916
16	GSK Investigational Site	Barcelona		Spain	08025
17	GSK Investigational Site	Barcelona		Spain	08035
18	GSK Investigational Site	Barcelona		Spain	08907
19	GSK Investigational Site	Madrid		Spain	28006
20	GSK Investigational Site	Madrid		Spain	28034
21	GSK Investigational Site	Madrid		Spain	28040
22	GSK Investigational Site	Madrid		Spain	28046
23	GSK Investigational Site	Sevilla		Spain	41013

Sponsors and Collaborators

ViiV Healthcare

Investigators

Study Director: GSK Clinical Trials, ViiV Healthcare

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

ViiV Healthcare

ClinicalTrials.gov Identifier:

NCT03784079

Other Study ID Numbers:

208132

First Posted:

Dec 21, 2018

Last Update Posted:

Feb 16, 2021

Last Verified:

Jan 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by ViiV Healthcare

HIV-1, Antiviral Effect, GSK3640254, Proof of Concept

Additional relevant MeSH terms:

HIV Infections

Study Results

Participant Flow

Recruitment Details	This was a randomized, double-blind, placebo-controlled, adaptive clinical trial to evaluate the antiviral effect, safety, tolerability and pharmacokinetic (PK)/pharmacodynamics (PD) of GSK3640254 over 10 days in study Part 1 and over 7 days in study Part 2.
Pre-assignment Detail	A total of 34 participants (14 participants in Part 1 and 20 participants in Part 2) were enrolled in this study. This study was conducted in France, Germany, Italy, South Africa and Spain.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 10 milligram (mg), capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Period Title: Part 1: Up to Day 24
STARTED	6	6	2	0	0	0	0
COMPLETED	6	6	2	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0
Period Title: Part 1: Up to Day 24
STARTED	0	0	0	6	6	6	2
COMPLETED	0	0	0	6	6	6	2
NOT COMPLETED	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo	Total
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Total of all reporting groups
Overall Participants	6	6	2	6	6	6	2	34
Age, Customized (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
19-64 years	6 100%	6 100%	2 100%	6 100%	6 100%	6 100%	2 100%	34 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	1 16.7%	0 0%	1 16.7%	0 0%	2 5.9%
Male	6 100%	6 100%	2 100%	5 83.3%	6 100%	5 83.3%	2 100%	32 94.1%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	2 33.3%	0 0%	0 0%	0 0%	0 0%	0 0%	1 50%	3 8.8%
Asian: South East Asian Heritage	1 16.7%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 2.9%
Black or African American	0 0%	0 0%	0 0%	1 16.7%	2 33.3%	1 16.7%	0 0%	4 11.8%
White: White/Caucasian/European Heritage	2 33.3%	5 83.3%	2 100%	5 83.3%	4 66.7%	5 83.3%	1 50%	24 70.6%
Multiple: American Indian or Alaska Native & White	1 16.7%	1 16.7%	0 0%	0 0%	0 0%	0 0%	0 0%	2 5.9%

Outcome Measures

1. Primary Outcome

Title	Part 1: Maximum Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at Day 11
Description	Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. A HIV-1 RNA polymerase chain reaction (PCR) assay with a lower limit of detection (LLOD) of 50 copies per milliliter was used. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Day 11

Outcome Measure Data

Analysis Population Description
Intent-To-Treat Exposed Population consisted of all participants who met study criteria and were enrolled into the study with documented evidence of having received at least 1 dose of treatment and at least one post-Baseline HIV-1 RNA measurement.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Mean (Standard Deviation) [Copies per milliliter]	-8605.8 (4604.40)	-100719.8 (89182.99)	-3406.5 (2591.55)

2. Primary Outcome

Title	Part 2: Maximum Change From Baseline in Plasma HIV-1 RNA at Day 8
Description	Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. An HIV-1 RNA PCR assay with an LLOD of 50 copies per milliliter was used. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Day 8

Outcome Measure Data

Analysis Population Description
Intent-To-Treat Exposed Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Mean (Standard Deviation) [Copies per milliliter]	-48655.0 (26269.41)	-37904.3 (38814.54)	-64904.2 (83798.67)	-123478.5 (175276.92)

3. Secondary Outcome

Title	Part 1: Number of Participants With Non-Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
Description	An adverse event (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 or other situations as per Medical or scientific judgment. Safety Population consisted of all participants who were enrolled into the study with documented evidence of having received at least 1 dose of randomized treatment.
Time Frame	Up to Day 24

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Non-SAEs	3 50%	5 83.3%	0 0%
SAEs	1 16.7%	0 0%	0 0%

4. Secondary Outcome

Title	Part 2: Number of Participants With Non-SAEs and SAEs
Description	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 or other situations as per Medical or scientific judgment.
Time Frame	Up to Day 12

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Non-SAEs	5 83.3%	4 66.7%	4 200%	0 0%
SAEs	0 0%	0 0%	1 50%	0 0%

5. Secondary Outcome

Title	Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Basophils	0.005 (0.0266)	-0.017 (0.0234)	0.015 (0.0212)
Eosinophils	-0.023 (0.1296)	0.058 (0.1134)	-0.025 (0.0212)
Lymphocytes	-0.027 (0.5267)	0.458 (0.4412)	0.070 (0.0566)
Monocytes	0.100 (0.1124)	-0.000 (0.0980)	0.055 (0.0212)
Neutrophils	-0.045 (0.4624)	-0.525 (0.8169)	0.345 (0.1485)
Leukocytes	0.02 (0.679)	-0.02 (1.057)	0.45 (0.212)
Platelet count	25.0 (46.35)	11.8 (12.04)	13.0 (2.83)

6. Secondary Outcome

Title	Part 1: Change From Baseline in Hematology Parameter: Hemoglobin
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Mean (Standard Deviation) [Grams per liter]	-4.2 (4.96)	-1.8 (5.98)	-1.0 (5.66)

7. Secondary Outcome

Title	Part 1: Change From Baseline in Hematology Parameter: Hematocrit
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Mean (Standard Deviation) [Proportion of red blood cells in blood]	-0.0117 (0.01684)	-0.0073 (0.01919)	-0.0010 (0.01838)

8. Secondary Outcome

Title	Part 1: Change From Baseline in Hematology Parameter: Erythrocytes
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Mean (Standard Deviation) [10^12 cells per liter]	-0.10 (0.190)	-0.07 (0.197)	0.00 (0.141)

9. Secondary Outcome

Title	Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Mean (Standard Deviation) [Femtoliter]	0.0 (0.89)	-0.3 (1.03)	0.0 (0.00)

10. Secondary Outcome

Title	Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Mean (Standard Deviation) [Picograms]	-0.08 (0.286)	0.03 (0.266)	-0.15 (0.071)

11. Secondary Outcome

Title	Part 1: Change From Baseline in Hematology Parameter: Reticulocytes/Erythrocyte
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: reticulocytes/erythrocyte (erythro). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Mean (Standard Deviation) [Percentage of reticulocytes in erythro]	0.0042 (0.00449)	0.0012 (0.00172)	0.0020 (0.00000)

12. Secondary Outcome

Title	Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count
Description	Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	5	6	6	2
Basophils, n=5,6,5,2	0.010 (0.0141)	0.020 (0.0237)	0.022 (0.0084)	-0.005 (0.0354)
Eosinophils, n=5,6,5,2	-0.066 (0.2145)	-0.047 (0.1775)	0.034 (0.0404)	0.020 (0.0000)
Lymphocytes, n=5,6,5,2	0.006 (0.4458)	-0.062 (0.4731)	0.536 (0.4766)	-0.110 (0.2687)
Monocytes, n=5,6,5,2	-0.020 (0.0869)	0.022 (0.1705)	-0.084 (0.1436)	-0.130 (0.1131)
Neutrophils, n=5,6,5,2	0.424 (0.6401)	1.678 (2.1754)	0.432 (0.7007)	-0.215 (0.3182)
Leukocytes, n=5,6,6,2	0.34 (0.385)	1.62 (2.244)	0.52 (1.211)	-0.45 (0.071)
Platelet count, n=4,6,6,2	1.5 (45.82)	17.5 (30.26)	16.0 (21.57)	4.5 (0.71)

13. Secondary Outcome

Title	Part 2: Change From Baseline in Hematology Parameter: Hemoglobin
Description	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	5	6	6	2
Mean (Standard Deviation) [Grams per liter]	-8.0 (5.10)	-4.7 (6.59)	-1.7 (7.31)	-8.0 (1.41)

14. Secondary Outcome

Title	Part 2: Change From Baseline in Hematology Parameter: Hematocrit
Description	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	5	6	6	2
Mean (Standard Deviation) [Proportion of red blood cells in blood]	-0.0230 (0.01762)	-0.0123 (0.02096)	-0.0058 (0.02094)	-0.0315 (0.01485)

15. Secondary Outcome

Title	Part 2: Change From Baseline in Hematology Parameter: Erythrocytes
Description	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	5	6	6	2
Mean (Standard Deviation) [10^12 cells per liter]	-0.24 (0.207)	-0.17 (0.216)	-0.08 (0.223)	-0.30 (0.000)

16. Secondary Outcome

Title	Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume
Description	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	5	6	6	2
Mean (Standard Deviation) [Femtoliter]	-0.2 (0.45)	0.2 (0.98)	0.2 (0.98)	-2.0 (2.83)

17. Secondary Outcome

Title	Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
Description	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	5	6	6	2
Mean (Standard Deviation) [Picograms]	-0.28 (0.850)	-0.05 (0.187)	-0.02 (0.337)	-0.05 (0.354)

18. Secondary Outcome

Title	Part 2: Change From Baseline in Hematology Parameter: Reticulocytes/Erythro
Description	Blood samples were collected to analyze the hematology parameter: reticulocytes/erythro. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	5	6	6	2
Mean (Standard Deviation) [Percentage of reticulocytes in erythro]	0.0030 (0.00235)	0.0017 (0.00258)	0.0007 (0.00350)	0.0020 (0.00283)

19. Secondary Outcome

Title	Part 1: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, High Density Lipoprotein (HDL) Cholesterol, Low Density Lipoprotein (LDL) Cholesterol
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Glucose, n=6,6,2	-0.20 (0.253)	0.28 (0.595)	0.00 (0.424)
Calcium, n=6,6,2	-0.007 (0.1343)	-0.027 (0.0468)	0.020 (0.0283)
Chloride, n=6,6,2	0.0 (2.10)	0.8 (3.06)	-0.5 (3.54)
Phosphate, n=6,6,2	0.042 (0.1594)	0.058 (0.1772)	-0.075 (0.1061)
Potassium, n=6,6,2	0.02 (0.240)	-0.03 (0.242)	-0.10 (0.000)
Magnesium, n=6,6,2	0.000 (0.0551)	-0.007 (0.0561)	-0.020 (0.0283)
Sodium, n=6,6,2	0.2 (2.40)	-0.8 (1.60)	-1.0 (1.41)
Urea, n=6,6,2	-0.08 (1.021)	-0.08 (0.801)	1.00 (0.000)

20. Secondary Outcome

Title	Part 1: Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST)
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
ALT	2.7 (7.79)	-1.7 (4.46)	9.5 (6.36)
ALP	10.5 (23.36)	-3.5 (4.64)	-4.0 (1.41)
AST	-0.5 (3.94)	-2.0 (8.60)	4.5 (2.12)

21. Secondary Outcome

Title	Part 1: Change From Baseline in Chemistry Parameters: Creatinine, Bilirubin
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: creatinine and bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Creatinine	1.77 (5.565)	-1.33 (4.291)	0.00 (0.000)
Bilirubin	-0.3 (3.20)	-2.0 (2.53)	3.0 (9.90)

22. Secondary Outcome

Title	Part 1: Change From Baseline in Chemistry Parameters: Protein
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameter: protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Mean (Standard Deviation) [Grams per liter]	-1.3 (4.93)	-1.0 (2.97)	1.0 (2.83)

23. Secondary Outcome

Title	Part 1: Change From Baseline in Chemistry Parameters: Amylase, Lipase
Description	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 6 (Day 11)

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified time points were analyzed. Amylase and lipase results were collected for two participants in GSK3640254 10 mg arm during Part 1 of the study. No data were collected for Placebo and GSK3640254 200 mg arms at Visit 6 (Day 11) due to delays in approval of Protocol Amendment 02 into which testing for amylase and lipase was added.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	2	0	0
Amylase	0.0 (11.31)
Lipase	-2.0 (2.83)

24. Secondary Outcome

Title	Part 2: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol
Description	Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	1
Glucose, n=6,6,6,1	-0.05 (0.327)	0.18 (1.085)	-0.03 (0.446)	0.50 (NA)
Calcium, n=6,6,6,1	-0.057 (0.0638)	-0.027 (0.0628)	0.030 (0.1002)	0.000 (NA)
Chloride, n=6,6,6,1	-0.7 (2.25)	-0.2 (1.47)	-0.7 (2.34)	-2.0 (NA)
Phosphate, n=6,6,6,1	-0.117 (0.2160)	0.067 (0.1211)	0.083 (0.1329)	0.000 (NA)
Potassium, n=6,6,6,1	-0.20 (0.261)	0.05 (0.383)	0.20 (0.210)	-0.10 (NA)
Magnesium, n=6,6,6,1	0.007 (0.0484)	0.007 (0.0413)	0.027 (0.0501)	0.000 (NA)
Sodium, n=6,6,6,1	-0.8 (2.23)	-0.3 (1.37)	-0.2 (1.72)	-4.0 (NA)
Urea, n=6,6,6,1	-0.42 (0.861)	-0.25 (1.037)	-0.33 (0.931)	-0.50 (NA)

25. Secondary Outcome

Title	Part 2: Change From Baseline in Chemistry Parameters: ALT, ALP, AST
Description	Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	1
ALT	-3.8 (6.62)	-1.2 (3.76)	-6.2 (8.33)	-1.0 (NA)
ALP	-3.2 (3.19)	-0.7 (5.35)	-1.8 (8.61)	-1.0 (NA)
AST	-5.2 (9.37)	0.3 (5.79)	-4.7 (7.37)	4.0 (NA)

26. Secondary Outcome

Title	Part 2: Change From Baseline in Chemistry Parameters: Creatinine, Bilirubin
Description	Blood samples were collected to analyze the chemistry parameters: creatinine and bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	1
Creatinine	1.35 (3.230)	-3.38 (2.230)	-0.17 (8.362)	-0.90 (NA)
Bilirubin	-0.3 (2.34)	1.3 (6.02)	0.3 (1.51)	0.0 (NA)

27. Secondary Outcome

Title	Part 2: Change From Baseline in Chemistry Parameters: Protein
Description	Blood samples were collected to analyze the chemistry parameter: protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	1
Mean (Standard Deviation) [Grams per liter]	-2.2 (3.25)	-0.8 (4.07)	1.5 (4.64)	-2.0 (NA)

28. Secondary Outcome

Title	Part 2: Change From Baseline in Chemistry Parameters: Amylase, Lipase
Description	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	1
Amylase	-2.3 (8.62)	0.8 (9.87)	6.7 (7.84)	-10.0 (NA)
Lipase	-1.0 (8.27)	-2.2 (6.37)	4.5 (8.29)	8.0 (NA)

29. Secondary Outcome

Title	Part 1: Change From Baseline in Urinalysis Parameter: Specific Gravity
Description	Urine samples were collected at Baseline and one sample between Days 8 to 10 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Mean (Standard Deviation) [Ratio]	0.0002 (0.00615)	0.0008 (0.00232)	0.0000 (0.00283)

30. Secondary Outcome

Title	Part 1: Change From Baseline in Urinalysis Parameter: Urobilinogen
Description	Urine samples were collected at Baseline and one sample between Days 8 to 10 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Mean (Standard Deviation) [Micromoles per liter]	4.50 (6.971)	0.00 (0.000)	0.00 (0.000)

31. Secondary Outcome

Title	Part 1: Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH)
Description	Urine samples were collected at Baseline and one sample between Days 8 to 10 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Mean (Standard Deviation) [pH]	0.17 (1.033)	-0.33 (0.683)	-0.50 (0.000)

32. Secondary Outcome

Title	Part 2: Change From Baseline in Urinalysis Parameter: Specific Gravity
Description	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Mean (Standard Deviation) [Ratio]	0.0010 (0.00746)	-0.0022 (0.00794)	0.0018 (0.00744)	-0.0110 (0.00424)

33. Secondary Outcome

Title	Part 2: Change From Baseline in Urinalysis Parameter: Urobilinogen
Description	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Mean (Standard Deviation) [Micromoles per liter]	0.00 (0.000)	4.50 (6.971)	0.00 (0.000)	0.00 (0.000)

34. Secondary Outcome

Title	Part 2: Change From Baseline in Urinalysis Parameter: pH
Description	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Mean (Standard Deviation) [pH]	0.17 (0.683)	-0.17 (0.683)	0.08 (0.492)	0.25 (0.354)

35. Secondary Outcome

Title	Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Description	SBP and DBP were measured in the semi-supine position with a completely automated device 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
SBP	-2.5 (8.41)	0.5 (9.65)	-1.5 (3.54)
DBP	-0.3 (14.50)	0.8 (4.67)	0.5 (0.71)

36. Secondary Outcome

Title	Part 1: Change From Baseline in Respiratory Rate
Description	Respiratory rate was measured in the semi-supine position with a completely automated device 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Mean (Standard Deviation) [Breaths per minute]	-1.0 (1.79)	0.2 (2.32)	-1.0 (1.41)

37. Secondary Outcome

Title	Part 1: Change From Baseline in Pulse Rate
Description	Pulse rate was measured in the semi-supine position with a completely automated device 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Mean (Standard Deviation) [Beats per minute]	-5.2 (4.36)	5.5 (10.99)	6.0 (2.83)

38. Secondary Outcome

Title	Part 2: Change From Baseline in SBP and DBP
Description	SBP and DBP were measured in the semi-supine position with a completely automated device 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
SBP	1.0 (8.27)	-2.2 (4.45)	7.3 (11.55)	1.0 (2.83)
DBP	-1.8 (2.40)	-1.0 (6.36)	2.3 (15.72)	-0.5 (7.78)

39. Secondary Outcome

Title	Part 2: Change From Baseline in Respiratory Rate
Description	Respiratory rate was measured in the semi-supine position with a completely automated device 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Mean (Standard Deviation) [Breaths per minute]	-0.2 (1.83)	0.2 (1.47)	-1.0 (4.47)	0.5 (2.12)

40. Secondary Outcome

Title	Part 2: Change From Baseline in Pulse Rate
Description	Pulse rate was measured in the semi-supine position with a completely automated device 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Mean (Standard Deviation) [Beats per minute]	4.2 (17.36)	2.0 (11.14)	2.8 (6.40)	10.5 (7.78)

41. Secondary Outcome

Title	Part 1: Change From Baseline in Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Bazett's Formula (QTcB), Corrected QT Interval Using Fridericia's Formula (QTcF)
Description	Twelve lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval, QTcB Interval and QTcF Interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1), Visit 5 (Days 8 to 10: Pre-dose, 2, 4 and 6 hours)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
PR Interval- Days 8 to 10: Pre-dose	-0.4 (5.32)	-7.6 (5.69)	-2.5 (2.12)
PR Interval- Days 8 to 10: 2 hours	1.4 (5.47)	-6.3 (9.71)	-11.5 (0.71)
PR Interval- Days 8 to 10: 4 hours	-0.1 (10.00)	0.2 (9.81)	-3.5 (0.71)
PR Interval- Days 8 to 10: 6 hours	1.4 (13.22)	-5.9 (3.93)	-25.0 (4.24)
QRS Duration- Days 8 to 10: Pre-dose	-3.1 (6.65)	-3.4 (9.90)	-5.3 (3.30)
QRS Duration- Days 8 to 10: 2 hours	-2.1 (6.60)	0.4 (6.27)	0.2 (4.01)
QRS Duration- Days 8 to 10: 4 hours	-3.3 (3.50)	-1.7 (6.75)	-1.3 (3.77)
QRS Duration- Days 8 to 10: 6 hours	-3.6 (5.56)	-2.9 (4.55)	-2.3 (13.20)
QT Interval- Days 8 to 10: Pre-dose	0.7 (8.15)	-2.7 (19.60)	-19.7 (21.21)
QT Interval- Days 8 to 10: 2 hours	-2.4 (17.61)	4.4 (20.33)	-28.7 (4.24)
QT Interval- Days 8 to 10: 4 hours	8.7 (18.43)	8.9 (13.72)	-25.2 (19.09)
QT Interval- Days 8 to 10: 6 hours	5.7 (16.48)	5.8 (14.19)	-24.2 (21.92)
QTcB Interval- Days 8 to 10: Pre-dose	1.65 (15.813)	3.60 (18.218)	-1.38 (6.435)
QTcB Interval- Days 8 to 10: 2 hours	-10.45 (22.433)	-4.60 (14.266)	-27.38 (32.315)
QTcB Interval- Days 8 to 10: 4 hours	0.77 (15.517)	-10.37 (20.176)	-30.23 (51.760)
QTcB Interval- Days 8 to 10: 6 hours	2.65 (13.391)	-9.15 (15.513)	-4.88 (11.102)
QTcF Interval- Days 8 to 10: Pre-dose	1.2 (10.75)	1.2 (9.56)	-7.7 (11.31)
QTcF Interval- Days 8 to 10: 2 hours	-7.5 (19.44)	-1.3 (14.06)	-27.7 (22.63)
QTcF Interval- Days 8 to 10: 4 hours	3.7 (15.18)	-3.7 (10.84)	-28.7 (41.01)
QTcF Interval- Days 8 to 10: 6 hours	4.0 (12.82)	-3.8 (13.06)	-12.2 (14.85)

42. Secondary Outcome

Title	Part 2: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcB, QTcF
Description	Twelve lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval, QTcB Interval and QTcF Interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1), Visit 5 (Day 7: Pre-dose, 2, 4 and 6 hours)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
PR Interval- Day 7: Pre-dose	9.7 (13.92)	-1.1 (6.89)	-7.3 (9.20)	-7.3 (0.47)
PR Interval- Day 7: 2 hours	6.1 (14.20)	-2.4 (7.90)	-3.1 (8.61)	6.2 (2.59)
PR Interval- Day 7: 4 hours	5.2 (22.87)	1.1 (8.56)	-8.3 (6.81)	4.7 (5.19)
PR Interval- Day 7: 6 hours	3.9 (16.80)	-2.3 (6.24)	-2.1 (5.82)	-7.8 (9.66)
QRS Duration- Day 7: Pre-dose	3.9 (5.11)	3.2 (7.81)	-0.4 (6.87)	2.3 (7.07)
QRS Duration- Day 7: 2 hours	2.4 (4.18)	0.7 (4.89)	-0.1 (8.45)	4.3 (1.41)
QRS Duration- Day 7: 4 hours	1.7 (4.06)	0.1 (4.41)	-3.1 (6.25)	3.8 (3.54)
QRS Duration- Day 7: 6 hours	0.5 (11.78)	-0.1 (3.04)	-0.8 (3.70)	2.8 (6.36)
QT Interval- Day 7: Pre-dose	-7.4 (33.78)	-1.6 (13.03)	5.0 (20.49)	3.2 (2.59)
QT Interval- Day 7: 2 hours	-24.4 (33.17)	-4.4 (8.90)	1.8 (12.60)	-0.3 (6.13)
QT Interval- Day 7: 4 hours	-12.8 (25.96)	4.2 (12.84)	-1.7 (13.65)	11.2 (19.56)
QT Interval- Day 7: 6 hours	-21.4 (36.18)	5.9 (12.19)	0.7 (12.92)	2.7 (7.54)
QTcB Interval- Day 7: Pre-dose	-4.16 (14.780)	0.34 (11.468)	3.45 (6.785)	-7.08 (2.569)
QTcB Interval- Day 7: 2 hours	2.90 (19.936)	0.09 (14.494)	-4.88 (17.444)	-18.23 (2.923)
QTcB Interval- Day 7: 4 hours	-6.96 (23.150)	-0.56 (13.559)	1.30 (14.341)	-23.83 (2.781)
QTcB Interval- Day 7: 6 hours	-3.26 (16.691)	4.17 (12.302)	-1.68 (10.181)	-9.83 (17.489)
QTcF Interval- Day 7: Pre-dose	-5.9 (18.89)	-0.5 (4.12)	4.1 (9.23)	-3.3 (0.94)
QTcF Interval- Day 7: 2 hours	-7.2 (22.91)	-1.3 (8.73)	-2.3 (12.87)	-12.3 (0.47)
QTcF Interval- Day 7: 4 hours	-9.4 (21.24)	1.2 (8.15)	0.6 (9.00)	-12.3 (4.71)
QTcF Interval- Day 7: 6 hours	-9.5 (19.08)	4.5 (5.69)	-0.8 (7.79)	-5.8 (8.72)

43. Secondary Outcome

Title	Part 1: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Baseline (Day 1): Basophils, n=6,5,2	0.052 (0.0279)	0.056 (0.0321)	0.030 (0.0000)
Days 8 to 10: Basophils, n=6,6,2	0.057 (0.0266)	0.037 (0.0186)	0.045 (0.0212)
Baseline (Day 1): Eosinophils, n=6,5,2	0.212 (0.1783)	0.150 (0.0616)	0.105 (0.0212)
Days 8 to 10: Eosinophils, n=6,6,2	0.188 (0.0873)	0.202 (0.1003)	0.080 (0.0424)
Baseline (Day 1): Lymphocytes, n=6,5,2	2.303 (0.5431)	1.810 (0.4341)	2.010 (0.0707)
Days 8 to 10: Lymphocytes, n=6,6,2	2.277 (0.4484)	2.217 (0.6693)	2.080 (0.1273)
Baseline (Day 1): Monocytes, n=6,5,2	0.552 (0.2033)	0.530 (0.1814)	0.460 (0.0000)
Days 8 to 10: Monocytes, n=6,6,2	0.652 (0.1907)	0.508 (0.2088)	0.515 (0.0212)
Baseline (Day 1): Neutrophils, n=6,5,2	2.935 (0.4803)	3.094 (0.7279)	1.840 (0.4101)
Days 8 to 10: Neutrophils, n=6,6,2	2.890 (0.6049)	2.635 (0.4068)	2.185 (0.2616)
Baseline (Day 1): Leukocytes, n=6,5,2	6.05 (1.071)	5.64 (1.172)	4.45 (0.495)
Days 8 to 10: Leukocytes, n=6,6,2	6.07 (0.929)	5.60 (1.158)	4.90 (0.283)
Baseline (Day 1): Platelet count, n=6,5,2	208.8 (38.48)	202.0 (39.26)	195.5 (12.02)
Days 8 to 10: Platelet count, n=6,6,2	233.8 (70.34)	205.0 (43.38)	208.5 (14.85)

44. Secondary Outcome

Title	Part 1: Absolute Values for Hematology Parameter: Hemoglobin
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 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.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Baseline (Day 1): n=6,5,2	144.2 (11.55)	135.4 (9.42)	148.0 (4.24)
Days 8 to 10: n=6,6,2	140.0 (12.18)	138.7 (12.72)	147.0 (9.90)

45. Secondary Outcome

Title	Part 1: Absolute Values for Hematology Parameter: Hematocrit
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 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.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Baseline (Day 1): n=6,5,2	0.4338 (0.02709)	0.4112 (0.02523)	0.4395 (0.01344)
Days 8 to 10: n=6,6,2	0.4222 (0.03456)	0.4158 (0.02827)	0.4385 (0.03182)

46. Secondary Outcome

Title	Part 1: Absolute Values for Hematology Parameter: Erythrocytes
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 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.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Baseline (Day 1): n=6,5,2	4.90 (0.228)	4.58 (0.259)	4.90 (0.283)
Days 8 to 10: n=6,6,2	4.80 (0.290)	4.63 (0.327)	4.90 (0.424)

47. Secondary Outcome

Title	Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 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.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Baseline (Day 1): n=6,5,2	88.5 (3.67)	90.2 (3.49)	90.0 (1.41)
Days 8 to 10: n=6,6,2	88.5 (4.09)	90.0 (2.28)	90.0 (1.41)

48. Secondary Outcome

Title	Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 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.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Baseline (Day 1): n=6,5,2	29.38 (1.780)	29.64 (0.879)	30.25 (0.636)
Days 8 to 10: n=6,6,2	29.30 (1.747)	29.97 (0.942)	30.10 (0.707)

49. Secondary Outcome

Title	Part 1: Absolute Values for Hematology Parameter: Reticulocytes/Erythro
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the hematology parameter: reticulocytes/erythro. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Baseline (Day 1): n=6,5,2	0.0137 (0.00726)	0.0078 (0.00349)	0.0110 (0.00424)
Days 8 to 10: n=6,6,2	0.0178 (0.01139)	0.0088 (0.00264)	0.0130 (0.00424)

50. Secondary Outcome

Title	Part 2: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count
Description	Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes and platelet count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Baseline (Day 1): Basophils, n=6,6,5,2	0.042 (0.0232)	0.042 (0.0117)	0.030 (0.0200)	0.040 (0.0283)
Day 7: Basophils, n=5,6,5,2	0.050 (0.0274)	0.062 (0.0223)	0.054 (0.0251)	0.035 (0.0071)
Baseline (Day 1): Eosinophils, n=6,6,5,2	0.402 (0.3307)	0.290 (0.2628)	0.320 (0.2542)	0.055 (0.0354)
Day 7: Eosinophils, n=5,6,5,2	0.316 (0.1780)	0.243 (0.1546)	0.210 (0.1239)	0.075 (0.0354)
Baseline (Day 1): Lymphocytes, n=6,6,5,2	1.990 (0.3013)	2.047 (0.6167)	2.236 (0.3010)	1.865 (0.3606)
Day 7: Lymphocytes, n=5,6,5,2	1.960 (0.3450)	1.985 (0.2983)	2.694 (0.7060)	1.755 (0.0919)
Baseline (Day 1): Monocytes, n=6,6,5,2	0.560 (0.2082)	0.477 (0.1442)	0.534 (0.1459)	0.435 (0.1061)
Day 7: Monocytes, n=5,6,5,2	0.530 (0.2210)	0.498 (0.2647)	0.414 (0.1467)	0.305 (0.0071)
Baseline (Day 1): Neutrophils, n=6,6,5,2	2.512 (1.2631)	2.442 (1.1951)	3.060 (0.5711)	2.280 (1.0465)
Day 7: Neutrophils, n=5,6,5,2	2.826 (1.1821)	4.120 (2.9025)	3.344 (0.6322)	2.065 (1.3647)
Baseline (Day 1): Leukocytes, n=6,6,5,2	5.50 (1.633)	5.28 (1.947)	6.20 (0.938)	4.65 (1.485)
Day 7: Leukocytes, n=5,6,6,2	5.66 (1.527)	6.90 (3.310)	6.55 (0.973)	4.20 (1.414)
Baseline (Day 1): Platelet count, n=5,6,5,2	276.6 (54.29)	236.7 (41.87)	232.2 (40.12)	197.0 (59.40)
Day 7: Platelet count, n=4,6,6,2	292.0 (77.06)	254.2 (37.39)	249.0 (38.72)	201.5 (60.10)

51. Secondary Outcome

Title	Part 2: Absolute Values for Hematology Parameter: Hemoglobin
Description	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.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Baseline (Day 1): n=6,6,5,2	136.3 (16.34)	149.2 (13.44)	141.2 (7.98)	147.0 (7.07)
Day 7: n=5,6,6,2	129.4 (19.55)	144.5 (7.87)	135.8 (11.02)	139.0 (8.49)

52. Secondary Outcome

Title	Part 2: Absolute Values for Hematology Parameter: Hematocrit
Description	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.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Baseline (Day 1): n=6,6,5,2	0.4037 (0.04646)	0.4505 (0.02992)	0.4222 (0.01879)	0.4330 (0.01838)
Day 7: n=5,6,6,2	0.3826 (0.05125)	0.4382 (0.01579)	0.4062 (0.03107)	0.4015 (0.03323)

53. Secondary Outcome

Title	Part 2: Absolute Values for Hematology Parameter: Erythrocytes
Description	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.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Baseline (Day 1): n=6,6,5,2	4.53 (0.476)	5.17 (0.450)	4.74 (0.230)	4.80 (0.000)
Day 7: n=5,6,6,2	4.26 (0.503)	5.00 (0.518)	4.52 (0.431)	4.50 (0.000)

54. Secondary Outcome

Title	Part 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume
Description	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.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Baseline (Day 1): n=6,6,5,2	88.8 (3.76)	87.8 (8.59)	89.2 (1.64)	91.0 (4.24)
Day 7: n=5,6,6,2	89.6 (3.44)	88.0 (8.53)	90.0 (2.97)	89.0 (7.07)

55. Secondary Outcome

Title	Part 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
Description	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.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Baseline (Day 1): n=6,6,5,2	30.07 (1.870)	29.15 (3.531)	29.80 (0.925)	30.95 (1.485)
Day 7: n=5,6,6,2	30.22 (2.017)	29.10 (3.553)	29.97 (0.898)	30.90 (1.838)

56. Secondary Outcome

Title	Part 2: Absolute Values for Hematology Parameter: Reticulocytes/Erythro
Description	Blood samples were collected to analyze the hematology parameter: reticulocytes/erythro. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Baseline (Day 1): n=6,6,5,2	0.0102 (0.00223)	0.0082 (0.00147)	0.0108 (0.00492)	0.0070 (0.00141)
Day 7: n=5,6,6,2	0.0124 (0.00297)	0.0098 (0.00160)	0.0107 (0.00344)	0.0090 (0.00141)

57. Secondary Outcome

Title	Part 1: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Baseline (Day 1): Glucose, n=6,6,2	5.28 (0.556)	4.88 (0.546)	5.40 (0.141)
Days 8 to 10: Glucose, n=6,6,2	5.08 (0.618)	5.17 (0.528)	5.40 (0.283)
Baseline (Day 1): Cholesterol, n=6,6,2	4.700 (1.2345)	4.058 (0.9641)	4.350 (0.6364)
Baseline (Day 1): Triglycerides, n=6,6,2	1.070 (0.4527)	1.150 (0.5114)	0.950 (0.4101)
Baseline (Day 1): Calcium, n=6,6,2	2.300 (0.1073)	2.313 (0.0961)	2.330 (0.0141)
Days 8 to 10: Calcium, n=6,6,2	2.293 (0.0816)	2.287 (0.0561)	2.350 (0.0424)
Baseline (Day 1): Chloride, n=6,6,2	104.2 (0.41)	105.8 (2.48)	105.0 (2.83)
Days 8 to 10: Chloride, n=6,6,2	104.2 (1.72)	106.7 (1.21)	104.5 (0.71)
Baseline (Day 1): Phosphate, n=6,6,2	1.117 (0.1835)	1.083 (0.1889)	1.200 (0.0707)
Days 8 to 10: Phosphate, n=6,6,2	1.158 (0.1882)	1.142 (0.2245)	1.125 (0.1768)
Baseline (Day 1): Potassium, n=6,6,2	4.10 (0.210)	4.30 (0.276)	4.15 (0.212)
Days 8 to 10: Potassium, n=6,6,2	4.12 (0.349)	4.27 (0.216)	4.05 (0.212)
Baseline (Day 1): Magnesium, n=6,6,2	0.847 (0.0393)	0.853 (0.0450)	0.880 (0.0283)
Days 8 to 10: Magnesium, n=6,6,2	0.847 (0.0561)	0.847 (0.0393)	0.860 (0.0000)
Baseline (Day 1): Sodium, n=6,6,2	138.3 (2.25)	139.8 (0.75)	139.0 (0.00)
Days 8 to 10: Sodium, n=6,6,2	138.5 (2.17)	139.0 (0.89)	138.0 (1.41)
Baseline (Day 1): Urea, n=6,6,2	5.33 (0.516)	5.83 (1.169)	5.00 (0.707)
Days 8 to 10: Urea, n=6,6,2	5.25 (1.037)	5.75 (0.524)	6.00 (0.707)
Baseline (Day 1): HDL cholesterol, n=6,6,2	1.192 (0.1960)	1.025 (0.0612)	1.075 (0.0354)
Baseline (Day 1): LDL cholesterol, n=6,6,2	3.017 (1.0452)	2.507 (0.7842)	2.840 (0.4808)

58. Secondary Outcome

Title	Part 1: Absolute Values for Chemistry Parameters: ALT, ALP, AST
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Baseline (Day 1): ALT	31.3 (15.67)	19.7 (15.82)	20.0 (8.49)
Days 8 to 10: ALT	34.0 (21.58)	18.0 (11.85)	29.5 (14.85)
Baseline (Day 1): ALP	62.0 (10.55)	62.3 (19.13)	63.0 (2.83)
Days 8 to 10: ALP	72.5 (27.68)	58.8 (16.46)	59.0 (1.41)
Baseline (Day 1): AST	26.7 (9.42)	23.3 (10.76)	20.0 (8.49)
Days 8 to 10: AST	26.2 (11.27)	21.3 (4.63)	24.5 (10.61)

59. Secondary Outcome

Title	Part 1: Absolute Values for Chemistry Parameters: Creatinine, Bilirubin
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameters: creatinine and bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Baseline (Day 1): Creatinine	82.05 (11.319)	81.35 (3.861)	88.40 (3.818)
Days 8 to 10: Creatinine	83.82 (13.674)	80.02 (6.239)	88.40 (3.818)
Baseline (Day 1): Bilirubin	11.7 (6.38)	8.0 (2.83)	15.0 (1.41)
Days 8 to 10: Bilirubin	11.3 (3.50)	6.0 (1.79)	18.0 (8.49)

60. Secondary Outcome

Title	Part 1: Absolute Values for Chemistry Parameters: Protein
Description	Blood samples were collected at Baseline and one sample between Days 8 to 10 to analyze the chemistry parameter: protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Baseline (Day 1)	72.2 (3.06)	70.3 (2.34)	69.0 (1.41)
Days 8 to 10	70.8 (3.60)	69.3 (5.05)	70.0 (1.41)

61. Secondary Outcome

Title	Part 1: Absolute Values for Chemistry Parameters: Amylase, Lipase
Description	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.
Time Frame	Baseline (Day 1) and Visit 6 (Day 11)

Outcome Measure Data

Analysis Population Description

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	2	0	0
Baseline (Day 1): Amylase	57.0 (11.31)
Day 11: Amylase	57.0 (0.00)
Baseline (Day 1): Lipase	28.5 (4.95)
Day 11: Lipase	26.5 (7.78)

62. Secondary Outcome

Title	Part 2: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol
Description	Blood samples were collected to analyze the chemistry parameters: glucose, cholesterol, triglycerides, calcium, chloride, phosphate, potassium, magnesium, sodium, urea, HDL cholesterol and LDL cholesterol. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Baseline (Day 1): Glucose, n=6,6,6,2	4.68 (0.306)	4.72 (0.928)	4.80 (0.456)	4.90 (0.849)
Day 7: Glucose, n=6,6,6,1	4.63 (0.408)	4.90 (0.190)	4.77 (0.320)	4.80 (NA)
Baseline (Day 1): Cholesterol, n=6,6,6,2	4.233 (0.6758)	4.375 (1.1626)	4.150 (0.8573)	3.400 (0.3536)
Baseline (Day 1): Triglycerides, n=6,6,6,2	1.183 (0.1924)	1.447 (0.6008)	1.120 (0.4879)	0.540 (0.1980)
Baseline (Day 1): Calcium, n=6,6,6,2	2.330 (0.0629)	2.320 (0.0980)	2.290 (0.0701)	2.280 (0.0849)
Day 7: Calcium, n=6,6,6,1	2.273 (0.0628)	2.293 (0.0766)	2.320 (0.0780)	2.220 (NA)
Baseline (Day 1): Chloride, n=6,6,6,2	103.0 (1.67)	102.2 (2.64)	103.7 (2.34)	105.5 (0.71)
Day 7: Chloride, n=6,6,6,1	102.3 (1.51)	102.0 (1.79)	103.0 (1.10)	104.0 (NA)
Baseline (Day 1): Phosphate, n=6,6,6,2	1.317 (0.1693)	1.108 (0.1281)	1.083 (0.1211)	0.950 (0.2828)
Day 7: Phosphate, n=6,6,6,1	1.200 (0.1265)	1.175 (0.1969)	1.167 (0.1329)	0.750 (NA)
Baseline (Day 1): Potassium, n=6,6,6,2	4.07 (0.476)	3.98 (0.325)	3.95 (0.164)	4.10 (0.424)
Day 7: Potassium, n=6,6,6,1	3.87 (0.273)	4.03 (0.242)	4.15 (0.122)	3.70 (NA)
Baseline (Day 1): Magnesium, n=6,6,6,2	0.790 (0.0395)	0.830 (0.0518)	0.803 (0.0320)	0.810 (0.0707)
Day 7: Magnesium, n=6,6,6,1	0.797 (0.0731)	0.837 (0.0427)	0.830 (0.0654)	0.760 (NA)
Baseline (Day 1): Sodium, n=6,6,6,2	137.7 (1.63)	138.5 (2.43)	137.8 (3.06)	140.5 (2.12)
Day 7: Sodium, n=6,6,6,1	136.8 (3.54)	138.2 (1.94)	137.7 (1.97)	138.0 (NA)
Baseline (Day 1): Urea, n=6,6,6,2	4.50 (1.517)	4.25 (1.508)	5.92 (1.068)	6.25 (2.475)
Day 7: Urea, n=6,6,6,1	4.08 (0.970)	4.00 (0.632)	5.58 (0.492)	4.00 (NA)
Baseline (Day 1): HDL cholesterol, n=6,6,6,2	1.242 (0.3277)	1.133 (0.3312)	1.200 (0.3194)	1.250 (0.0707)
Baseline (Day 1): LDL cholesterol, n=6,6,6,2	2.448 (0.6649)	2.578 (0.8267)	2.437 (0.6955)	1.905 (0.3748)

63. Secondary Outcome

Title	Part 2: Absolute Values for Chemistry Parameters: ALT, ALP, AST
Description	Blood samples were collected to analyze the chemistry parameters: ALT, ALP and AST. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Baseline (Day 1): ALT, n=6,6,6,2	18.3 (14.07)	17.8 (7.63)	33.2 (23.07)	34.5 (6.36)
Day 7: ALT, n=6,6,6,1	14.5 (7.66)	16.7 (5.24)	27.0 (18.00)	29.0 (NA)
Baseline (Day 1): ALP, n=6,6,6,2	63.3 (15.08)	63.7 (4.68)	60.8 (9.00)	43.0 (18.38)
Day 7: ALP, n=6,6,6,1	60.2 (16.53)	63.0 (5.25)	59.0 (5.18)	55.0 (NA)
Baseline (Day 1): AST, n=6,6,6,2	26.8 (15.39)	18.5 (6.60)	26.7 (8.14)	50.0 (39.60)
Day 7: AST, n=6,6,6,1	21.7 (6.74)	18.8 (3.31)	22.0 (3.74)	26.0 (NA)

64. Secondary Outcome

Title	Part 2: Absolute Values for Chemistry Parameters: Creatinine, Bilirubin
Description	Blood samples were collected to analyze the chemistry parameters: creatinine and bilirubin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Baseline (Day 1): Creatinine, n=6,6,6,2	71.30 (12.207)	73.67 (7.120)	73.52 (12.761)	86.65 (13.789)
Day 7: Creatinine, n=6,6,6,1	72.65 (14.109)	70.28 (8.269)	73.35 (8.195)	76.00 (NA)
Baseline (Day 1): Bilirubin, n=6,6,6,2	10.0 (5.66)	9.3 (1.03)	7.7 (3.44)	11.0 (7.07)
Day 7: Bilirubin, n=6,6,6,1	9.7 (4.97)	10.7 (5.47)	8.0 (2.83)	6.0 (NA)

65. Secondary Outcome

Title	Part 2: Absolute Values for Chemistry Parameters: Protein
Description	Blood samples were collected to analyze the chemistry parameter: protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Baseline (Day 1): n=6,6,6,2	78.8 (12.78)	73.3 (5.50)	76.7 (10.03)	73.5 (0.71)
Day 7: n=6,6,6,1	76.7 (12.01)	72.5 (5.13)	78.2 (8.93)	72.0 (NA)

66. Secondary Outcome

Title	Part 2: Absolute Values for Chemistry Parameters: Amylase, Lipase
Description	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.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Baseline (Day 1): Amylase, n=6,6,6,2	47.2 (18.15)	51.0 (21.65)	55.2 (18.61)	56.0 (25.46)
Day 7: Amylase, n=6,6,6,1	44.8 (17.81)	51.8 (22.71)	61.8 (25.86)	64.0 (NA)
Baseline (Day 1): Lipase, n=6,6,6,2	26.5 (14.08)	29.7 (10.95)	43.2 (32.32)	26.0 (14.14)
Day 7: Lipase, n=6,6,6,1	25.5 (11.64)	27.5 (13.40)	47.7 (34.70)	44.0 (NA)

67. Secondary Outcome

Title	Part 1: Absolute Values for Urinalysis Parameter: Specific Gravity
Description	Urine samples were collected at Baseline and one sample between Days 8 to 10 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.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Baseline (Day 1)	1.0238 (0.00677)	1.0233 (0.00320)	1.0240 (0.00283)
Days 8 to 10	1.0240 (0.00533)	1.0242 (0.00279)	1.0240 (0.00000)

68. Secondary Outcome

Title	Part 1: Absolute Values for Urinalysis Parameter: Urobilinogen
Description	Urine samples were collected at Baseline and one sample between Days 8 to 10 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.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Baseline (Day 1)	3.40 (0.000)	3.40 (0.000)	3.40 (0.000)
Days 8 to 10	7.90 (6.971)	3.40 (0.000)	3.40 (0.000)

69. Secondary Outcome

Title	Part 1: Absolute Values for Urinalysis Parameter: pH
Description	Urine samples were collected at Baseline and one sample between Days 8 to 10 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.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Baseline (Day 1)	5.67 (0.931)	5.75 (0.689)	5.75 (0.354)
Days 8 to 10	5.83 (0.753)	5.42 (0.585)	5.25 (0.354)

70. Secondary Outcome

Title	Part 2: Absolute Values for Urinalysis Parameter: Specific Gravity
Description	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.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Baseline (Day 1)	1.0223 (0.00866)	1.0272 (0.00360)	1.0255 (0.00918)	1.0375 (0.00495)
Day 7	1.0233 (0.00686)	1.0250 (0.00522)	1.0273 (0.00327)	1.0265 (0.00919)

71. Secondary Outcome

Title	Part 2: Absolute Values for Urinalysis Parameter: Urobilinogen
Description	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.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Baseline (Day 1)	3.40 (0.000)	3.40 (0.000)	3.40 (0.000)	3.40 (0.000)
Day 7	3.40 (0.000)	7.90 (6.971)	3.40 (0.000)	3.40 (0.000)

72. Secondary Outcome

Title	Part 2: Absolute Values for Urinalysis Parameter: pH
Description	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.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Baseline (Day 1)	5.33 (0.258)	5.83 (0.753)	5.25 (0.418)	5.50 (0.000)
Day 7	5.50 (0.775)	5.67 (0.258)	5.33 (0.258)	5.75 (0.354)

73. Secondary Outcome

Title	Part 1: Absolute Values for SBP and DBP
Description	SBP and DBP were measured in the semi-supine position with a completely automated device 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.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Baseline (Day 1): SBP	120.2 (13.36)	121.8 (12.25)	106.0 (11.31)
Days 8 to 10: SBP	117.7 (8.87)	122.3 (7.94)	104.5 (7.78)
Baseline (Day 1): DBP	70.3 (17.32)	66.7 (10.80)	64.0 (5.66)
Days 8 to 10: DBP	70.0 (6.81)	67.5 (9.91)	64.5 (4.95)

74. Secondary Outcome

Title	Part 1: Absolute Values for Respiratory Rate
Description	Respiratory rate was measured in the semi-supine position with a completely automated device 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.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Baseline (Day 1)	16.0 (2.61)	16.2 (3.31)	15.0 (4.24)
Days 8 to 10	15.0 (1.26)	16.3 (2.73)	14.0 (2.83)

75. Secondary Outcome

Title	Part 1: Absolute Values for Pulse Rate
Description	Pulse rate was measured in the semi-supine position with a completely automated device 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.
Time Frame	Baseline (Day 1) and Visit 5 (Days 8 to 10)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
Baseline (Day 1)	81.8 (18.25)	65.8 (14.22)	60.0 (2.83)
Days 8 to 10	76.7 (21.13)	71.3 (11.93)	66.0 (5.66)

76. Secondary Outcome

Title	Part 2: Absolute Values for SBP and DBP
Description	SBP and DBP were measured in the semi-supine position with a completely automated device 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.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Baseline (Day 1): SBP	117.0 (7.95)	116.5 (11.04)	112.2 (9.93)	105.5 (2.12)
Day 7: SBP	118.0 (12.07)	114.3 (8.36)	119.5 (8.87)	106.5 (4.95)
Baseline (Day 1): DBP	71.5 (4.51)	74.0 (4.69)	71.8 (12.89)	71.0 (12.73)
Day 7: DBP	69.7 (4.50)	73.0 (5.06)	74.2 (5.27)	70.5 (4.95)

77. Secondary Outcome

Title	Part 2: Absolute Values for Respiratory Rate
Description	Respiratory rate was measured in the semi-supine position with a completely automated device 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.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Baseline (Day 1)	17.3 (2.66)	17.2 (1.17)	17.2 (2.40)	16.0 (0.00)
Day 7	17.2 (2.56)	17.3 (2.07)	16.2 (2.23)	16.5 (2.12)

78. Secondary Outcome

Title	Part 2: Absolute Values for Pulse Rate
Description	Pulse rate was measured in the semi-supine position with a completely automated device 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.
Time Frame	Baseline (Day 1) and Visit 5 (Day 7)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
Baseline (Day 1)	68.3 (9.91)	74.5 (8.36)	77.0 (10.16)	64.5 (13.44)
Day 7	72.5 (16.34)	76.5 (7.87)	79.8 (12.45)	75.0 (5.66)

79. Secondary Outcome

Title	Part 1: Absolute Values for ECG Parameters: PR, QRS, QT, QTcB and QTcF Intervals
Description	Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, QTcF interval and QTcB interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time Frame	Baseline (Day 1), Visit 5 (Days 8 to 10: Pre-dose, 2, 4 and 6 hours)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 1: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6	2
PR Interval- Baseline (Day 1)	136.6 (14.49)	168.4 (15.48)	176.5 (27.58)
PR Interval- Days 8 to 10: Pre-dose	136.2 (15.26)	160.8 (19.60)	174.0 (29.70)
PR Interval- Days 8 to 10: 2 hours	138.0 (14.46)	162.2 (11.53)	165.0 (28.28)
PR Interval- Days 8 to 10: 4 hours	136.5 (12.10)	168.7 (13.81)	173.0 (28.28)
PR Interval- Days 8 to 10: 6 hours	138.0 (9.10)	162.5 (15.06)	151.5 (23.33)
QRS Duration- Baseline (Day 1)	93.1 (4.54)	95.7 (6.85)	85.8 (11.08)
QRS Duration- Days 8 to 10: Pre-dose	90.0 (7.46)	92.3 (7.74)	80.5 (7.78)
QRS Duration- Days 8 to 10: 2 hours	91.0 (6.36)	96.2 (7.17)	86.0 (7.07)
QRS Duration- Days 8 to 10: 4 hours	89.8 (5.91)	94.0 (6.42)	84.5 (14.85)
QRS Duration- Days 8 to 10: 6 hours	89.5 (7.04)	92.8 (10.11)	83.5 (2.12)
QT Interval- Baseline (Day 1)	367.6 (26.04)	378.7 (26.75)	372.7 (29.70)
QT Interval- Days 8 to 10: Pre-dose	368.3 (23.35)	376.0 (31.46)	353.0 (8.49)
QT Interval- Days 8 to 10: 2 hours	365.2 (25.39)	383.2 (26.84)	344.0 (25.46)
QT Interval- Days 8 to 10: 4 hours	376.3 (22.70)	387.7 (29.34)	347.5 (10.61)
QT Interval- Days 8 to 10: 6 hours	373.3 (26.48)	384.5 (25.37)	348.5 (7.78)
QTcB Interval- Baseline (Day 1)	412.15 (31.539)	397.75 (22.914)	388.43 (39.598)
QTcB Interval- Days 8 to 10: Pre-dose	413.80 (42.176)	401.35 (22.923)	387.05 (33.163)
QTcB Interval- Days 8 to 10: 2 hours	401.70 (37.316)	393.15 (26.290)	361.05 (7.283)
QTcB Interval- Days 8 to 10: 4 hours	412.92 (42.143)	387.38 (24.454)	358.20 (12.162)
QTcB Interval- Days 8 to 10: 6 hours	414.80 (34.569)	388.60 (23.893)	383.55 (28.496)
QTcF Interval- Baseline (Day 1)	396.2 (17.67)	391.2 (19.11)	383.2 (36.06)
QTcF Interval- Days 8 to 10: Pre-dose	397.3 (25.34)	392.3 (20.64)	375.5 (24.75)
QTcF Interval- Days 8 to 10: 2 hours	388.7 (22.72)	389.8 (22.89)	355.5 (13.44)
QTcF Interval- Days 8 to 10: 4 hours	399.8 (25.87)	387.5 (21.27)	354.5 (4.95)
QTcF Interval- Days 8 to 10: 6 hours	400.2 (19.22)	387.3 (22.03)	371.0 (21.21)

80. Secondary Outcome

Title	Part 2: Absolute Values for ECG Parameters: PR, QRS, QT, QTcB and QTcF Intervals
Description	Twelve lead ECGs were obtained to measure PR interval, QRS duration, QT interval, QTcF interval and QTcB interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time Frame	Baseline (Day 1), Visit 5 (Day 7: Pre-dose, 2, 4 and 6 hours)

Outcome Measure Data

Analysis Population Description
Safety Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg	Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	2
PR Interval- Baseline (Day 1)	156.8 (33.02)	162.9 (29.73)	162.8 (20.83)	144.3 (6.13)
PR Interval- Day 7: Pre-dose	166.5 (25.62)	161.8 (31.06)	155.5 (26.10)	137.0 (5.66)
PR Interval- Day 7: 2 hours	162.8 (28.34)	160.5 (28.73)	159.7 (26.04)	150.5 (3.54)
PR Interval- Day 7: 4 hours	162.0 (24.85)	164.0 (31.51)	154.5 (20.51)	149.0 (11.31)
PR Interval- Day 7: 6 hours	160.7 (24.81)	160.7 (27.25)	160.7 (25.90)	136.5 (3.54)
QRS Duration- Baseline (Day 1)	92.6 (10.22)	95.1 (21.97)	88.9 (7.40)	85.7 (11.31)
QRS Duration- Day 7: Pre-dose	96.5 (8.14)	98.3 (28.86)	88.5 (3.99)	88.0 (4.24)
QRS Duration- Day 7: 2 hours	95.0 (9.78)	95.8 (19.29)	88.8 (4.49)	90.0 (12.73)
QRS Duration- Day 7: 4 hours	94.3 (8.89)	95.2 (18.94)	85.8 (4.88)	89.5 (7.78)
QRS Duration- Day 7: 6 hours	93.2 (10.61)	95.0 (21.29)	88.2 (8.11)	88.5 (17.68)
QT Interval- Baseline (Day 1)	386.6 (28.86)	355.9 (25.37)	362.5 (19.45)	378.8 (1.18)
QT Interval- Day 7: Pre-dose	379.2 (33.30)	354.3 (31.94)	367.5 (26.93)	382.0 (1.41)
QT Interval- Day 7: 2 hours	362.2 (31.24)	351.5 (25.05)	364.3 (17.32)	378.5 (4.95)
QT Interval- Day 7: 4 hours	373.8 (24.25)	360.2 (23.07)	360.8 (18.64)	390.0 (18.38)
QT Interval- Day 7: 6 hours	365.2 (34.53)	361.8 (25.88)	363.2 (19.50)	381.5 (6.36)
QTcB Interval- Baseline (Day 1)	402.88 (26.814)	398.24 (25.587)	411.18 (15.858)	406.73 (20.742)
QTcB Interval- Day 7: Pre-dose	398.72 (26.663)	398.58 (21.075)	414.63 (17.816)	399.65 (18.173)
QTcB Interval- Day 7: 2 hours	405.78 (10.923)	398.33 (33.672)	406.30 (27.565)	388.50 (17.819)
QTcB Interval- Day 7: 4 hours	395.92 (22.851)	397.68 (20.635)	412.48 (27.377)	382.90 (17.961)
QTcB Interval- Day 7: 6 hours	399.62 (19.074)	402.42 (22.916)	409.50 (19.009)	396.90 (3.253)
QTcF Interval- Baseline (Day 1)	397.4 (24.60)	383.5 (23.72)	394.1 (12.71)	397.3 (13.67)
QTcF Interval- Day 7: Pre-dose	391.5 (24.01)	383.0 (24.90)	398.2 (18.58)	394.0 (12.73)
QTcF Interval- Day 7: 2 hours	390.2 (12.16)	382.2 (30.20)	391.8 (22.44)	385.0 (14.14)
QTcF Interval- Day 7: 4 hours	388.0 (18.21)	384.7 (20.42)	394.7 (18.91)	385.0 (18.38)
QTcF Interval- Day 7: 6 hours	387.8 (11.29)	388.0 (21.76)	393.3 (17.20)	391.5 (4.95)

81. Secondary Outcome

Title	Part 1: Area Under the Plasma Concentration Time Curve From Zero to 24 (AUC[0-24]) Following Administration of GSK3640254 on Day 1
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Pharmacokinetic (PK) Population consisted of all participants who received GSK3640254 and underwent plasma PK sampling during the study.
Time Frame	Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	5	6
Geometric Mean (Geometric Coefficient of Variation) [Hours*microgram per milliliter]	0.6946 (13.5)	12.3929 (91.3)

82. Secondary Outcome

Title	Part 1: Maximum Observed Concentration (Cmax) Following Administration of GSK3640254 on Day 1
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	0.0591 (177.4)	0.9381 (82.3)

83. Secondary Outcome

Title	Part 1: Time to Maximum Observed Concentration (Tmax) Following Administration of GSK3640254 on Day 1
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6
Median (Full Range) [Hours]	2.9250	5.5250

84. Secondary Outcome

Title	Part 1: Concentration at 24 Hours Post-dose (C24) Following Administration of GSK3640254 on Day 1
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	0.0180 (27.5)	0.3553 (92.7)

85. Secondary Outcome

Title	Part 1: Absorption Lag Time (Tlag) Following Administration of GSK3640254 on Day 1
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6
Median (Full Range) [Hours]	0.500	0.000

86. Secondary Outcome

Title	Part 2: AUC(0-24) Following Administration of GSK3640254 on Day 1
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [Hours*microgram per milliliter]	3.2527 (31.7)	6.1228 (38.8)	14.0335 (36.6)

87. Secondary Outcome

Title	Part 2: Cmax Following Administration of GSK3640254 on Day 1
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	0.2316 (30.5)	0.4329 (33.6)	0.9178 (41.5)

88. Secondary Outcome

Title	Part 2: Tmax Following Administration of GSK3640254 on Day 1
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6
Median (Full Range) [Hours]	4.4167	4.0750	5.5083

89. Secondary Outcome

Title	Part 2: C24 Following Administration of GSK3640254 on Day 1
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	0.0951 (33.7)	0.1856 (36.2)	0.4207 (33.8)

90. Secondary Outcome

Title	Part 2: Tlag Following Administration of GSK3640254 on Day 1
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6
Median (Full Range) [Hours]	0.483	0.000	0.000

91. Secondary Outcome

Title	Part 1: Area Under the Plasma Drug Concentration-time Curve From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6
Geometric Mean (Geometric Coefficient of Variation) [Hours*microgram per milliliter]	0.9082 (44.7)	27.9363 (18.4)

92. Secondary Outcome

Title	Part 1: Cmax Following Repeat Dose Administration of GSK3640254 on Days 8 to 10
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	0.0549 (41.3)	1.8559 (19.5)

93. Secondary Outcome

Title	Part 1: Tmax Following Repeat Dose Administration of GSK3640254 on Days 8 to 10
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6
Median (Full Range) [Hours]	4.0167	5.4833

94. Secondary Outcome

Title	Part 1: Pre-dose Concentration (C0) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10
Description	Blood sample was collected at indicated time point for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Days 8 to 10: Pre-dose

Outcome Measure Data

Analysis Population Description
PK Population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	5
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	0.0268 (41.6)	0.6928 (33.6)

95. Secondary Outcome

Title	Part 1: Concentration at End of Dosing Interval (Ctau) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	0.0267 (47.0)	0.7033 (29.6)

96. Secondary Outcome

Title	Part 1: Apparent Terminal Phase Half-life (t1/2) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6
Median (Full Range) [Hours]	NA	NA

97. Secondary Outcome

Title	Part 1: Apparent Oral Clearance (CL/F) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6
Geometric Mean (Geometric Coefficient of Variation) [Milliliter per hour]	11010.5393 (44.7)	7159.1443 (18.4)

98. Secondary Outcome

Title	Part 2: AUC(0-tau) Following Repeat Dose Administration of GSK3640254 on Day 7
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [Hours*microgram per milliliter]	7.4626 (26.8)	11.8256 (26.7)	29.2952 (27.9)

99. Secondary Outcome

Title	Part 2: Cmax Following Repeat Dose Administration of GSK3640254 on Day 7
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	0.4692 (20.6)	0.7470 (23.7)	1.8574 (26.0)

100. Secondary Outcome

Title	Part 2: Tmax Following Repeat Dose Administration of GSK3640254 on Day 7
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6
Median (Full Range) [Hours]	4.0583	4.5750	4.0750

101. Secondary Outcome

Title	Part 2: C0 Following Repeat Dose Administration of GSK3640254 on Day 7
Description	Blood sample was collected at indicated time point for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Day 7: Pre-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	0.2155 (24.2)	0.3575 (38.0)	0.7520 (38.8)

102. Secondary Outcome

Title	Part 2: Ctau Following Repeat Dose Administration of GSK3640254 on Day 7
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	0.2187 (30.1)	0.3599 (31.1)	0.7979 (34.1)

103. Secondary Outcome

Title	Part 2: t1/2 Following Repeat Dose Administration of GSK3640254 on Day 7
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6
Median (Full Range) [Hours]	NA	NA	NA

104. Secondary Outcome

Title	Part 2: CL/F Following Repeat Dose Administration of GSK3640254 on Day 7
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.
Time Frame	Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [Milliliter per hour]	5360.0526 (26.8)	6764.9862 (26.7)	4778.9430 (27.9)

105. Secondary Outcome

Title	Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 AUC(0-tau)
Description	Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Statistical analysis for relationship between PK parameters (AUC) and PD measures (Change from Baseline in plasma HIV-1 RNA) were explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: maximum response (Emax), PK parameter value that attains 50 percent (%) of the maximal effect (EC50) and residual variability (s2e). PK/PD Population consisted of participants who met criteria for Per-Protocol and Pharmacokinetic Population analysis sets and who underwent PD sampling during the study.
Time Frame	Baseline (Day 1) and Day 8

Outcome Measure Data

Analysis Population Description
PK/PD Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Arm/Group Description	Participants received GSK3640254 10 milligram (mg), capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	6	6
Mean (Standard Deviation) [Copies per milliliter]	12071.4 (42117.29)	-113331.4 (89475.00)	-48655.0 (26269.41)	-37904.3 (38814.54)	-64861.5 (83728.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: GSK3640254 10 mg, Part 1: GSK3640254 200 mg, Part 1: Placebo, Part 2: Placebo, Part 2: GSK3640254 140 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Emax
	Estimated Value	-1.937
	Confidence Interval	(2-Sided) 95% -2.484 to -1.389
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1: GSK3640254 10 mg, Part 1: GSK3640254 200 mg, Part 1: Placebo, Part 2: Placebo, Part 2: GSK3640254 140 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	EC50
	Estimated Value	7.094
	Confidence Interval	(2-Sided) 95% 0.585 to 13.602
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part 1: GSK3640254 10 mg, Part 1: GSK3640254 200 mg, Part 1: Placebo, Part 2: Placebo, Part 2: GSK3640254 140 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	s2e
	Estimated Value	0.137
	Confidence Interval	(2-Sided) 95% 0.062 to 0.212
	Parameter Dispersion	Type: Value:
	Estimation Comments

106. Secondary Outcome

Title	Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 Cmax
Description	Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Statistical analysis for relationship between PK parameters (Cmax) and PD measures (Change from Baseline in plasma HIV-1 RNA) were explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: Emax, EC50 and s2e.
Time Frame	Baseline (Day 1) and Day 8

Outcome Measure Data

Analysis Population Description
PK/PD Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Arm/Group Description	Participants received GSK3640254 10 milligram (mg), capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	6	6
Mean (Standard Deviation) [Copies per milliliter]	12071.4 (42117.29)	-113331.4 (89475.00)	-48655.0 (26269.41)	-37904.3 (38814.54)	-64861.5 (83728.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: GSK3640254 10 mg, Part 1: GSK3640254 200 mg, Part 1: Placebo, Part 2: Placebo, Part 2: GSK3640254 140 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Emax
	Estimated Value	-1.929
	Confidence Interval	(2-Sided) 95% -2.479 to -1.379
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1: GSK3640254 10 mg, Part 1: GSK3640254 200 mg, Part 1: Placebo, Part 2: Placebo, Part 2: GSK3640254 140 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	EC50
	Estimated Value	0.446
	Confidence Interval	(2-Sided) 95% 0.030 to 0.861
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part 1: GSK3640254 10 mg, Part 1: GSK3640254 200 mg, Part 1: Placebo, Part 2: Placebo, Part 2: GSK3640254 140 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	s2e
	Estimated Value	0.139
	Confidence Interval	(2-Sided) 95% 0.063 to 0.216
	Parameter Dispersion	Type: Value:
	Estimation Comments

107. Secondary Outcome

Title	Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 Ctau
Description	Plasma samples were collected for quantitative analysis of HIV-1 RNA. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Statistical analysis for relationship between PK parameters (Ctau) and PD measures (Change from Baseline in plasma HIV-1 RNA) were explored using a frequentist three parameter Emax non-linear model. The model parameters estimated included: Emax, EC50 and s2e.
Time Frame	Baseline (Day 1) and Day 8

Outcome Measure Data

Analysis Population Description
PK/PD Population.

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Arm/Group Description	Participants received GSK3640254 10 milligram (mg), capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6	6	6
Mean (Standard Deviation) [Copies per milliliter]	12071.4 (42117.29)	-113331.4 (89475.00)	-48655.0 (26269.41)	-37904.3 (38814.54)	-64861.5 (83728.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: GSK3640254 10 mg, Part 1: GSK3640254 200 mg, Part 1: Placebo, Part 2: Placebo, Part 2: GSK3640254 140 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Emax
	Estimated Value	-1.926
	Confidence Interval	(2-Sided) 95% -2.498 to -1.354
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1: GSK3640254 10 mg, Part 1: GSK3640254 200 mg, Part 1: Placebo, Part 2: Placebo, Part 2: GSK3640254 140 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	EC50
	Estimated Value	0.197
	Confidence Interval	(2-Sided) 95% 0.007 to 0.386
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part 1: GSK3640254 10 mg, Part 1: GSK3640254 200 mg, Part 1: Placebo, Part 2: Placebo, Part 2: GSK3640254 140 mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	s2e
	Estimated Value	0.144
	Confidence Interval	(2-Sided) 95% 0.065 to 0.222
	Parameter Dispersion	Type: Value:
	Estimation Comments

108. Secondary Outcome

Title	Part 1: Accumulation Ratio Following Repeat Dose Administration of GSK3640254
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The accumulation ratios (Ro) were calculated as Ro_AUC equal to (=) AUC(0-tau) Days 8 to 10 divided by (/) AUC(0-24) Day 1; Ro_Cmax=Cmax Days 8 to 10/Cmax Day 1; and Ro_Ctau=Ctau Days 8 to 10/C24 Day 1.
Time Frame	Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population. Only those participants with data available at the specified time points were analyzed (indicated by n=X in category titles).

Arm/Group Title	Part 1: GSK3640254 10 mg	Part 1: GSK3640254 200 mg
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
Measure Participants	6	6
Ro_AUC(0-tau), n=5,6	1.5352 (24.5)	2.2542 (72.1)
Ro_Cmax, n=6,6	0.9287 (171.7)	1.9785 (69.4)
Ro_Ctau, n=6,6	1.4790 (22.2)	1.9796 (61.2)

109. Secondary Outcome

Title	Part 2: Accumulation Ratio Following Repeat Dose Administration of GSK3640254
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The accumulation ratios (Ro) were calculated as Ro_AUC=AUC(0-tau) Day 7/AUC(0-24) Day 1; Ro_Cmax=Cmax Day 7/Cmax Day 1; and Ro_Ctau=Ctau Day 7/C24 Day 1.
Time Frame	Days 1 and 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	Part 2: GSK3640254 40 mg	Part 2: GSK3640254 80 mg	Part 2: GSK3640254 140 mg
Arm/Group Description	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
Measure Participants	6	6	6
Ro_AUC(0-tau)	2.2943 (11.2)	1.9314 (18.6)	2.0875 (29.2)
Ro_Cmax	2.0258 (24.4)	1.7258 (17.6)	2.0236 (37.5)
Ro_Ctau	2.2985 (6.4)	1.9389 (20.8)	1.8967 (16.0)

110. Secondary Outcome

Title	Part 1 and Part 2: Dose Proportionality of GSK3640254 Administered on Day 1 Based on AUC(0-24)
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.
Time Frame	Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	GSK3640254 10 mg to 200 mg
Arm/Group Description	In Part 1, participants received GSK3640254 10 mg, 200 mg, capsules, orally for 10 days and in Part 2, participants received GSK3640254 40 mg, 80 mg, 140 mg, capsules, orally for 7 days.
Measure Participants	30
Number (90% Confidence Interval) [Slope of log dose]	1.018

111. Secondary Outcome

Title	Part 1 and Part 2: Dose Proportionality of GSK3640254 Administered on Day 1 Based on Cmax
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.
Time Frame	Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	GSK3640254 10 mg to 200 mg
Arm/Group Description	In Part 1, participants received GSK3640254 10 mg, 200 mg, capsules, orally for 10 days and in Part 2, participants received GSK3640254 40 mg, 80 mg, 140 mg, capsules, orally for 7 days.
Measure Participants	30
Number (90% Confidence Interval) [Slope of log dose]	0.964

112. Secondary Outcome

Title	Part 1 and Part 2: Dose Proportionality of GSK3640254 Administered on Day 1 Based on C24
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.
Time Frame	Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	GSK3640254 10 mg to 200 mg
Arm/Group Description	In Part 1, participants received GSK3640254 10 mg, 200 mg, capsules, orally for 10 days and in Part 2, participants received GSK3640254 40 mg, 80 mg, 140 mg, capsules, orally for 7 days.
Measure Participants	30
Number (90% Confidence Interval) [Slope of log dose]	1.061

113. Secondary Outcome

Title	Part 1 and Part 2: Dose Proportionality of GSK3640254 Following Repeat Dose Administration Based on AUC(0-tau)
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.
Time Frame	Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	GSK3640254 10 mg to 200 mg
Arm/Group Description	In Part 1, participants received GSK3640254 10 mg, 200 mg, capsules, orally for 10 days and in Part 2, participants received GSK3640254 40 mg, 80 mg, 140 mg, capsules, orally for 7 days.
Measure Participants	30
Number (90% Confidence Interval) [Slope of log dose]	1.179

114. Secondary Outcome

Title	Part 1 and Part 2: Dose Proportionality of GSK3640254 Following Repeat Dose Administration Based on Cmax
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.
Time Frame	Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	GSK3640254 10 mg to 200 mg
Arm/Group Description	In Part 1, participants received GSK3640254 10 mg, 200 mg, capsules, orally for 10 days and in Part 2, participants received GSK3640254 40 mg, 80 mg, 140 mg, capsules, orally for 7 days.
Measure Participants	30
Number (90% Confidence Interval) [Slope of log dose]	1.204

115. Secondary Outcome

Title	Part 1 and Part 2: Dose Proportionality of GSK3640254 Following Repeat Dose Administration Based on Ctau
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis. Dose proportionality was assessed using Power model with logarithm of dose as fixed effect. Slope and 90% confidence interval for the slope are presented.
Time Frame	Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose; Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK Population.

Arm/Group Title	GSK3640254 10 mg to 200 mg
Arm/Group Description	In Part 1, participants received GSK3640254 10 mg, 200 mg, capsules, orally for 10 days and in Part 2, participants received GSK3640254 40 mg, 80 mg, 140 mg, capsules, orally for 7 days.
Measure Participants	30
Number (90% Confidence Interval) [Slope of log dose]	1.137

Adverse Events

	Part 1: GSK3640254 10 mg		Part 1: GSK3640254 200 mg		Part 1: Placebo		Part 2: GSK3640254 40 mg		Part 2: GSK3640254 80 mg		Part 2: GSK3640254 140 mg		Part 2: Placebo
Time Frame	Part 1: up to Day 24; Part 2: up to Day 12
Adverse Event Reporting Description	Safety Population consisted of all participants who were enrolled into the study with documented evidence of having received at least 1 dose of randomized treatment.

Arm/Group Title	Part 1: GSK3640254 10 mg		Part 1: GSK3640254 200 mg		Part 1: Placebo		Part 2: GSK3640254 40 mg		Part 2: GSK3640254 80 mg		Part 2: GSK3640254 140 mg		Part 2: Placebo
Arm/Group Description	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.		Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.		Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.		Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.		Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.		Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.		Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/2 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/2 (0%)
Serious Adverse Events
	Part 1: GSK3640254 10 mg		Part 1: GSK3640254 200 mg		Part 1: Placebo		Part 2: GSK3640254 40 mg		Part 2: GSK3640254 80 mg		Part 2: GSK3640254 140 mg		Part 2: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		0/6 (0%)		0/2 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/2 (0%)
Cardiac disorders
Congestive cardiomyopathy	1/6 (16.7%)	1	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Infections and infestations
Anal abscess	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/2 (0%)	0
Other (Not Including Serious) Adverse Events
	Part 1: GSK3640254 10 mg		Part 1: GSK3640254 200 mg		Part 1: Placebo		Part 2: GSK3640254 40 mg		Part 2: GSK3640254 80 mg		Part 2: GSK3640254 140 mg		Part 2: Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/6 (50%)		5/6 (83.3%)		0/2 (0%)		5/6 (83.3%)		4/6 (66.7%)		4/6 (66.7%)		0/2 (0%)
Blood and lymphatic system disorders
Lymphadenopathy	1/6 (16.7%)	1	1/6 (16.7%)	1	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Neutropenia	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/2 (0%)	0
Cardiac disorders
Myocarditis	1/6 (16.7%)	1	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Gastrointestinal disorders
Diarrhoea	1/6 (16.7%)	1	1/6 (16.7%)	1	0/2 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Abdominal pain	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	3	0/6 (0%)	0	0/2 (0%)	0
Vomiting	1/6 (16.7%)	1	1/6 (16.7%)	1	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Constipation	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/2 (0%)	0
Nausea	1/6 (16.7%)	1	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
General disorders
Asthenia	0/6 (0%)	0	1/6 (16.7%)	1	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Fatigue	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	1/6 (16.7%)	2	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Nodule	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/2 (0%)	0
Pyrexia	0/6 (0%)	0	1/6 (16.7%)	1	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Infections and infestations
Nasopharyngitis	0/6 (0%)	0	2/6 (33.3%)	2	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Meningococcal infection	1/6 (16.7%)	1	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Pharyngitis	0/6 (0%)	0	1/6 (16.7%)	1	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Upper respiratory tract infection	0/6 (0%)	0	1/6 (16.7%)	1	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Urinary tract infection	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/2 (0%)	0
Viral infection	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Investigations
Alanine aminotransferase increased	1/6 (16.7%)	1	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Aspartate aminotransferase increased	1/6 (16.7%)	1	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Metabolism and nutrition disorders
Hyperglycaemia	1/6 (16.7%)	1	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Insulin resistance	1/6 (16.7%)	1	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Vitamin D deficiency	1/6 (16.7%)	1	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Musculoskeletal and connective tissue disorders
Pain in extremity	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/2 (0%)	0
Spinal pain	1/6 (16.7%)	1	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Nervous system disorders
Headache	0/6 (0%)	0	2/6 (33.3%)	2	0/2 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	1/6 (16.7%)	1	0/2 (0%)	0
Migraine	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/2 (0%)	0
Presyncope	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Renal and urinary disorders
Chromaturia	1/6 (16.7%)	1	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/6 (0%)	0	2/6 (33.3%)	2	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/2 (0%)	0
Catarrh	0/6 (0%)	0	1/6 (16.7%)	1	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Epistaxis	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis atopic	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/2 (0%)	0
Pruritus	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/2 (0%)	0
Rash maculo-papular	0/6 (0%)	0	0/6 (0%)	0	0/2 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/2 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/Title	GSK Response Center
Organization	ViiV Healthcare
Phone	866-435-7343
Email	GSKClinicalSupportHD@gsk.com

Responsible Party:

ViiV Healthcare

ClinicalTrials.gov Identifier:

NCT03784079

Other Study ID Numbers:

208132

First Posted:

Dec 21, 2018

Last Update Posted:

Feb 16, 2021

Last Verified:

Jan 1, 2021