A Proof of Concept Study of GSK3640254 in Human Immunodef... | NCT03784079

Description Module

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.

Label	Type	Description	Intervention Names
Part 1: GSK3640254 10 mg	Experimental	Participants will receive GSK3640254 10 milligram (mg), capsules, orally for 10 days.	Drug: GSK3640254
Part 1: GSK3640254 200 mg	Experimental	Participants will receive GSK3640254 200 mg, capsules, orally for 10 days.	Drug: GSK3640254
Part 1: Placebo	Placebo Comparator	Participants will receive placebo capsules, orally for 10 days.	Drug: Placebo matching GSK3640254 Mesylate salt
Part 2: GSK3640254 40 mg	Experimental	Participants will receive GSK3640254 40 mg, capsules, orally for 7 days.	Drug: GSK3640254
Part 2: GSK3640254 80 mg	Experimental	Participants will receive GSK3640254 80 mg, capsules, orally for 7 days.	Drug: GSK3640254
Part 2: GSK3640254 140 mg	Experimental

Name	Type	Description	Arm Group Labels	Other Names
GSK3640254	Drug	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.	Part 1: GSK3640254 10 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Part 1: Maximum Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at 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.	Baseline (Day 1) and Day 11
Part 2: Maximum Change From Baseline in Plasma HIV-1 RNA at 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.	Baseline (Day 1) and Day 8

Secondary Outcomes

Measure	Description	Time Frame
Part 1: Number of Participants With Non-Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)	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.

Eligibility Module

Eligibility Criteria

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.

Name	Affiliation	Role
GSK Clinical Trials	ViiV Healthcare	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Bakersfield	California	93301	United States
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
34996113	Derived	Spinner CD, Felizarta F, Rizzardini G, Philibert P, Mitha E, Domingo P, Stephan CJ, DeGrosky M, Bainbridge V, Zhan J, Dumitrescu TP, Jeffrey JL, Xu J, Halliday F, Gan J, Johnson M, Gartland M, Joshi SR, Lataillade M. Phase IIa Proof-of-Concept Evaluation of the Antiviral Efficacy, Safety, Tolerability, and Pharmacokinetics of the Next-Generation Maturation Inhibitor GSK3640254. Clin Infect Dis. 2022 Sep 14;75(5):786-794. doi: 10.1093/cid/ciab1065.

ID	Title	Description
FG000	Part 1: GSK3640254 10 mg	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.
FG001	Part 1: GSK3640254 200 mg

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 26, 2019	Dec 3, 2020

Arm/Group Information

ID	Title	Description
BG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
BG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
BG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
BG003	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
BG004	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
BG005	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
BG006	Part 2: Placebo	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
BG007	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Part 1: Maximum Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) at 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.

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.

Posted

Mean

Standard Deviation

Copies per milliliter

Baseline (Day 1) and Day 11

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Units	Counts
Participants	OG0006 OG0016 OG0022

Title

Denominators

Categories

Title	Measurements
	OG000-8605.8± 4604.40 OG001-100719.8± 89182.99 OG002-3406.5± 2591.55

Primary

Part 2: Maximum Change From Baseline in Plasma HIV-1 RNA at 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.

Intent-To-Treat Exposed Population.

Posted

Mean

Standard Deviation

Copies per milliliter

Baseline (Day 1) and Day 8

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

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

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.

Safety Population.

Posted

Count of Participants

Participants

Up to Day 24

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo

Secondary

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

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per Medical or scientific judgment.

Safety Population.

Posted

Count of Participants

Participants

Up to Day 12

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count

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.

Safety Population.

Posted

Mean

Standard Deviation

10^9 cells per liter

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Change From Baseline in Hematology Parameter: Hemoglobin

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.

Safety Population.

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Change From Baseline in Hematology Parameter: Hematocrit

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.

Safety Population.

Posted

Mean

Standard Deviation

Proportion of red blood cells in blood

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Change From Baseline in Hematology Parameter: Erythrocytes

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.

Safety Population.

Posted

Mean

Standard Deviation

10^12 cells per liter

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

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.

Safety Population.

Posted

Mean

Standard Deviation

Femtoliter

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

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.

Safety Population.

Posted

Mean

Standard Deviation

Picograms

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Change From Baseline in Hematology Parameter: Reticulocytes/Erythrocyte

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.

Safety Population.

Posted

Mean

Standard Deviation

Percentage of reticulocytes in erythro

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 2: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count

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.

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

Posted

Mean

Standard Deviation

10^9 cells per liter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Change From Baseline in Hematology Parameter: Hemoglobin

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

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

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Change From Baseline in Hematology Parameter: Hematocrit

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

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

Posted

Mean

Standard Deviation

Proportion of red blood cells in blood

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Change From Baseline in Hematology Parameter: Erythrocytes

Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

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

Posted

Mean

Standard Deviation

10^12 cells per liter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

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

Posted

Mean

Standard Deviation

Femtoliter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

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

Posted

Mean

Standard Deviation

Picograms

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Change From Baseline in Hematology Parameter: Reticulocytes/Erythro

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.

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

Posted

Mean

Standard Deviation

Percentage of reticulocytes in erythro

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

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

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.

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

Posted

Mean

Standard Deviation

Millimoles per liter

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Change From Baseline in Chemistry Parameters: Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST)

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.

Safety Population.

Posted

Mean

Standard Deviation

International units per liter

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Change From Baseline in Chemistry Parameters: Creatinine, Bilirubin

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.

Safety Population.

Posted

Mean

Standard Deviation

Micromoles per liter

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Change From Baseline in Chemistry Parameters: Protein

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.

Safety Population.

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Change From Baseline in Chemistry Parameters: Amylase, Lipase

Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

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.

Posted

Mean

Standard Deviation

Units per liter

Baseline (Day 1) and Visit 6 (Day 11)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo

Secondary

Part 2: Change From Baseline in Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol

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.

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

Posted

Mean

Standard Deviation

Millimoles per liter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg

Secondary

Part 2: Change From Baseline in Chemistry Parameters: ALT, ALP, AST

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.

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

Posted

Mean

Standard Deviation

International units per liter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Change From Baseline in Chemistry Parameters: Creatinine, Bilirubin

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.

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

Posted

Mean

Standard Deviation

Micromoles per liter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Change From Baseline in Chemistry Parameters: Protein

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.

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

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Change From Baseline in Chemistry Parameters: Amylase, Lipase

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

Posted

Mean

Standard Deviation

Units per liter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 1: Change From Baseline in Urinalysis Parameter: Specific Gravity

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.

Safety Population.

Posted

Mean

Standard Deviation

Ratio

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Change From Baseline in Urinalysis Parameter: Urobilinogen

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.

Safety Population.

Posted

Mean

Standard Deviation

Micromoles per liter

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Change From Baseline in Urinalysis Parameter: Potential of Hydrogen (pH)

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.

Safety Population.

Posted

Mean

Standard Deviation

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo

Secondary

Part 2: Change From Baseline in Urinalysis Parameter: Specific Gravity

Urine samples were collected to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Safety Population.

Posted

Mean

Standard Deviation

Ratio

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Change From Baseline in Urinalysis Parameter: Urobilinogen

Urine samples were collected to analyze the urinalysis parameter: urobilinogen. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Safety Population.

Posted

Mean

Standard Deviation

Micromoles per liter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG003

Secondary

Part 2: Change From Baseline in Urinalysis Parameter: pH

Urine samples were collected to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Safety Population.

Posted

Mean

Standard Deviation

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

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.

Safety Population.

Posted

Mean

Standard Deviation

Millimeters of mercury

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Change From Baseline in Respiratory Rate

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.

Safety Population.

Posted

Mean

Standard Deviation

Breaths per minute

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Change From Baseline in Pulse Rate

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.

Safety Population.

Posted

Mean

Standard Deviation

Beats per minute

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 2: Change From Baseline in SBP and DBP

Safety Population.

Posted

Mean

Standard Deviation

Millimeters of mercury

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Change From Baseline in Respiratory Rate

Safety Population.

Posted

Mean

Standard Deviation

Breaths per minute

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Change From Baseline in Pulse Rate

Safety Population.

Posted

Mean

Standard Deviation

Beats per minute

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

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)

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.

Safety Population.

Posted

Mean

Standard Deviation

Milliseconds

Baseline (Day 1), Visit 5 (Days 8 to 10: Pre-dose, 2, 4 and 6 hours)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 2: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcB, QTcF

Safety Population.

Posted

Mean

Standard Deviation

Milliseconds

Baseline (Day 1), Visit 5 (Day 7: Pre-dose, 2, 4 and 6 hours)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 1: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count

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

Posted

Mean

Standard Deviation

10^9 cells per liter

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Absolute Values for Hematology Parameter: Hemoglobin

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

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Absolute Values for Hematology Parameter: Hematocrit

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

Posted

Mean

Standard Deviation

Proportion of red blood cells in blood

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Absolute Values for Hematology Parameter: Erythrocytes

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

Posted

Mean

Standard Deviation

10^12 cells per liter

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume

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

Posted

Mean

Standard Deviation

Femtoliter

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

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

Posted

Mean

Standard Deviation

Picograms

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Absolute Values for Hematology Parameter: Reticulocytes/Erythro

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.

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

Posted

Mean

Standard Deviation

Percentage of reticulocytes in erythro

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 2: Absolute Values for Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Leukocytes, Platelet Count

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

Posted

Mean

Standard Deviation

10^9 cells per liter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Absolute Values for Hematology Parameter: Hemoglobin

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

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

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG003

Secondary

Part 2: Absolute Values for Hematology Parameter: Hematocrit

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

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

Posted

Mean

Standard Deviation

Proportion of red blood cells in blood

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG003

Secondary

Part 2: Absolute Values for Hematology Parameter: Erythrocytes

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

Posted

Mean

Standard Deviation

10^12 cells per liter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG003

Secondary

Part 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Volume

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

Posted

Mean

Standard Deviation

Femtoliter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Absolute Values for Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin

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

Posted

Mean

Standard Deviation

Picograms

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Absolute Values for Hematology Parameter: Reticulocytes/Erythro

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

Posted

Mean

Standard Deviation

Percentage of reticulocytes in erythro

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 1: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol

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

Posted

Mean

Standard Deviation

Millimoles per liter

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo

Secondary

Part 1: Absolute Values for Chemistry Parameters: ALT, ALP, AST

Safety Population.

Posted

Mean

Standard Deviation

International units per liter

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Absolute Values for Chemistry Parameters: Creatinine, Bilirubin

Safety Population.

Posted

Mean

Standard Deviation

Micromoles per liter

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Absolute Values for Chemistry Parameters: Protein

Safety Population.

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Absolute Values for Chemistry Parameters: Amylase, Lipase

Posted

Mean

Standard Deviation

Units per liter

Baseline (Day 1) and Visit 6 (Day 11)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 2: Absolute Values for Chemistry Parameters: Glucose, Cholesterol, Triglycerides, Calcium, Chloride, Phosphate, Potassium, Magnesium, Sodium, Urea, HDL Cholesterol, LDL Cholesterol

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

Posted

Mean

Standard Deviation

Millimoles per liter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Absolute Values for Chemistry Parameters: ALT, ALP, AST

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

Posted

Mean

Standard Deviation

International units per liter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG003

Secondary

Part 2: Absolute Values for Chemistry Parameters: Creatinine, Bilirubin

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

Posted

Mean

Standard Deviation

Micromoles per liter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG003

Secondary

Part 2: Absolute Values for Chemistry Parameters: Protein

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.

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

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG003

Secondary

Part 2: Absolute Values for Chemistry Parameters: Amylase, Lipase

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

Posted

Mean

Standard Deviation

Units per liter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG003

Secondary

Part 1: Absolute Values for Urinalysis Parameter: Specific Gravity

Safety Population.

Posted

Mean

Standard Deviation

Ratio

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Absolute Values for Urinalysis Parameter: Urobilinogen

Safety Population.

Posted

Mean

Standard Deviation

Micromoles per liter

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Absolute Values for Urinalysis Parameter: pH

Safety Population.

Posted

Mean

Standard Deviation

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 2: Absolute Values for Urinalysis Parameter: Specific Gravity

Safety Population.

Posted

Mean

Standard Deviation

Ratio

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG003

Secondary

Part 2: Absolute Values for Urinalysis Parameter: Urobilinogen

Safety Population.

Posted

Mean

Standard Deviation

Micromoles per liter

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG003	Part 2: Placebo

Secondary

Part 2: Absolute Values for Urinalysis Parameter: pH

Safety Population.

Posted

Mean

Standard Deviation

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 1: Absolute Values for SBP and DBP

Safety Population.

Posted

Mean

Standard Deviation

Millimeters of mercury

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Absolute Values for Respiratory Rate

Safety Population.

Posted

Mean

Standard Deviation

Breaths per minute

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1: Absolute Values for Pulse Rate

Safety Population.

Posted

Mean

Standard Deviation

Beats per minute

Baseline (Day 1) and Visit 5 (Days 8 to 10)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 2: Absolute Values for SBP and DBP

Safety Population.

Posted

Mean

Standard Deviation

Millimeters of mercury

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG003	Part 2: Placebo

Secondary

Part 2: Absolute Values for Respiratory Rate

Safety Population.

Posted

Mean

Standard Deviation

Breaths per minute

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG003	Part 2: Placebo

Secondary

Part 2: Absolute Values for Pulse Rate

Safety Population.

Posted

Mean

Standard Deviation

Beats per minute

Baseline (Day 1) and Visit 5 (Day 7)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG003	Part 2: Placebo

Secondary

Part 1: Absolute Values for ECG Parameters: PR, QRS, QT, QTcB and QTcF Intervals

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.

Safety Population.

Posted

Mean

Standard Deviation

Milliseconds

Baseline (Day 1), Visit 5 (Days 8 to 10: Pre-dose, 2, 4 and 6 hours)

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 2: Absolute Values for ECG Parameters: PR, QRS, QT, QTcB and QTcF Intervals

Safety Population.

Posted

Mean

Standard Deviation

Milliseconds

Baseline (Day 1), Visit 5 (Day 7: Pre-dose, 2, 4 and 6 hours)

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG003	Part 2: Placebo

Secondary

Part 1: Area Under the Plasma Concentration Time Curve From Zero to 24 (AUC[0-24]) Following Administration of GSK3640254 on Day 1

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.

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

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours*microgram per milliliter

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Units	Counts
Participants

Secondary

Part 1: Maximum Observed Concentration (Cmax) Following Administration of GSK3640254 on Day 1

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Geometric Mean

Geometric Coefficient of Variation

Microgram per milliliter

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Units	Counts
Participants	OG000

Secondary

Part 1: Time to Maximum Observed Concentration (Tmax) Following Administration of GSK3640254 on Day 1

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Median

Full Range

Hours

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Units	Counts
Participants	OG000

Secondary

Part 1: Concentration at 24 Hours Post-dose (C24) Following Administration of GSK3640254 on Day 1

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Geometric Mean

Geometric Coefficient of Variation

Microgram per milliliter

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Units	Counts
Participants	OG000

Secondary

Part 1: Absorption Lag Time (Tlag) Following Administration of GSK3640254 on Day 1

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Median

Full Range

Hours

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Units	Counts
Participants	OG000

Secondary

Part 2: AUC(0-24) Following Administration of GSK3640254 on Day 1

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours*microgram per milliliter

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Cmax Following Administration of GSK3640254 on Day 1

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Geometric Mean

Geometric Coefficient of Variation

Microgram per milliliter

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Tmax Following Administration of GSK3640254 on Day 1

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Median

Full Range

Hours

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Units	Counts

Secondary

Part 2: C24 Following Administration of GSK3640254 on Day 1

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Geometric Mean

Geometric Coefficient of Variation

Microgram per milliliter

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Tlag Following Administration of GSK3640254 on Day 1

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Median

Full Range

Hours

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Units	Counts

Secondary

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

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours*microgram per milliliter

Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Units	Counts
Participants

Secondary

Part 1: Cmax Following Repeat Dose Administration of GSK3640254 on Days 8 to 10

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Geometric Mean

Geometric Coefficient of Variation

Microgram per milliliter

Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Units	Counts
Participants	OG000

Secondary

Part 1: Tmax Following Repeat Dose Administration of GSK3640254 on Days 8 to 10

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Median

Full Range

Hours

Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Units	Counts
Participants	OG000

Secondary

Part 1: Pre-dose Concentration (C0) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10

Blood sample was collected at indicated time point for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

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

Posted

Geometric Mean

Geometric Coefficient of Variation

Microgram per milliliter

Days 8 to 10: Pre-dose

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Units	Counts
Participants	OG000

Secondary

Part 1: Concentration at End of Dosing Interval (Ctau) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Geometric Mean

Geometric Coefficient of Variation

Microgram per milliliter

Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Units	Counts
Participants	OG000

Secondary

Part 1: Apparent Terminal Phase Half-life (t1/2) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Median

Full Range

Hours

Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Units	Counts
Participants	OG000

Secondary

Part 1: Apparent Oral Clearance (CL/F) Following Repeat Dose Administration of GSK3640254 on Days 8 to 10

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Geometric Mean

Geometric Coefficient of Variation

Milliliter per hour

Days 8 to 10: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Units	Counts
Participants	OG000

Secondary

Part 2: AUC(0-tau) Following Repeat Dose Administration of GSK3640254 on Day 7

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours*microgram per milliliter

Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Cmax Following Repeat Dose Administration of GSK3640254 on Day 7

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Geometric Mean

Geometric Coefficient of Variation

Microgram per milliliter

Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: Tmax Following Repeat Dose Administration of GSK3640254 on Day 7

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Median

Full Range

Hours

Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Units

Secondary

Part 2: C0 Following Repeat Dose Administration of GSK3640254 on Day 7

Blood sample was collected at indicated time point for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Geometric Mean

Geometric Coefficient of Variation

Microgram per milliliter

Day 7: Pre-dose

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Units

Secondary

Part 2: Ctau Following Repeat Dose Administration of GSK3640254 on Day 7

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Geometric Mean

Geometric Coefficient of Variation

Microgram per milliliter

Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 2: t1/2 Following Repeat Dose Administration of GSK3640254 on Day 7

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Median

Full Range

Hours

Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Units

Secondary

Part 2: CL/F Following Repeat Dose Administration of GSK3640254 on Day 7

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3640254. The PK parameters were calculated by standard non-compartmental analysis.

PK Population.

Posted

Geometric Mean

Geometric Coefficient of Variation

Milliliter per hour

Day 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 AUC(0-tau)

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.

PK/PD Population.

Posted

Mean

Standard Deviation

Copies per milliliter

Baseline (Day 1) and Day 8

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	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.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Secondary

Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 Cmax

PK/PD Population.

Posted

Mean

Standard Deviation

Copies per milliliter

Baseline (Day 1) and Day 8

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	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.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 1 and Part 2: Change From Baseline in Plasma HIV-1 RNA Relative to Day 8 Ctau

PK/PD Population.

Posted

Mean

Standard Deviation

Copies per milliliter

Baseline (Day 1) and Day 8

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	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.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG002	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 1: Accumulation Ratio Following Repeat Dose Administration of GSK3640254

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.

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

Posted

Geometric Mean

Geometric Coefficient of Variation

Ratio

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

ID	Title	Description
OG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.
OG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.

Units	Counts

Secondary

Part 2: Accumulation Ratio Following Repeat Dose Administration of GSK3640254

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.

PK Population.

Posted

Geometric Mean

Geometric Coefficient of Variation

Ratio

Days 1 and 7: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG001	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.
OG002	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.

Secondary

Part 1 and Part 2: Dose Proportionality of GSK3640254 Administered on Day 1 Based on AUC(0-24)

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.

PK Population.

Posted

Number

90% Confidence Interval

Slope of log dose

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	GSK3640254 10 mg to 200 mg	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.

Units	Counts
Participants	OG000

Secondary

Part 1 and Part 2: Dose Proportionality of GSK3640254 Administered on Day 1 Based on Cmax

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.

PK Population.

Posted

Number

90% Confidence Interval

Slope of log dose

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	GSK3640254 10 mg to 200 mg	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.

Units	Counts
Participants	OG000

Secondary

Part 1 and Part 2: Dose Proportionality of GSK3640254 Administered on Day 1 Based on C24

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.

PK Population.

Posted

Number

90% Confidence Interval

Slope of log dose

Day 1: Pre-dose and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose

ID	Title	Description
OG000	GSK3640254 10 mg to 200 mg	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.

Units	Counts
Participants	OG000

Secondary

Part 1 and Part 2: Dose Proportionality of GSK3640254 Following Repeat Dose Administration Based on AUC(0-tau)

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.

PK Population.

Posted

Number

90% Confidence Interval

Slope of log dose

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

ID	Title	Description
OG000	GSK3640254 10 mg to 200 mg	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.

Units	Counts
Participants	OG000

Secondary

Part 1 and Part 2: Dose Proportionality of GSK3640254 Following Repeat Dose Administration Based on Cmax

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.

PK Population.

Posted

Number

90% Confidence Interval

Slope of log dose

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

ID	Title	Description
OG000	GSK3640254 10 mg to 200 mg	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.

Units	Counts
Participants	OG000

Secondary

Part 1 and Part 2: Dose Proportionality of GSK3640254 Following Repeat Dose Administration Based on Ctau

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.

PK Population.

Posted

Number

90% Confidence Interval

Slope of log dose

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

ID	Title	Description
OG000	GSK3640254 10 mg to 200 mg	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.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part 1: GSK3640254 10 mg	Participants received GSK3640254 10 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	6	1	6	3	6
EG001	Part 1: GSK3640254 200 mg	Participants received GSK3640254 200 mg, capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	6	0	6	5	6
EG002	Part 1: Placebo	Participants received placebo capsules, orally for 10 days. Participants were followed for up to 14 days post last dose of study treatment.	2	0	2	0	2
EG003	Part 2: GSK3640254 40 mg	Participants received GSK3640254 40 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	6	0	6	5	6
EG004	Part 2: GSK3640254 80 mg	Participants received GSK3640254 80 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	6	0	6	4	6
EG005	Part 2: GSK3640254 140 mg	Participants received GSK3640254 140 mg, capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	6	1	6	4	6
EG006	Part 2: Placebo	Participants received placebo capsules, orally for 7 days. Participants were followed for up to 5 days post last dose of study treatment.	2	0	2	0	2

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Headache	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected6 at risk EG0020 events0 affected2 at risk EG0031 events1 affected6 at risk EG0040 events0 affected6 at risk EG0051 events1 affected6 at risk EG0060 events0 affected2 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected6 at risk EG0020 events0 affected2 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected6 at risk EG0020 events0 affected2 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Asthenia	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Catarrh	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Chromaturia	Renal and urinary disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Dermatitis atopic	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Fatigue	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Insulin resistance	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Meningococcal infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Migraine	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Myocarditis	Cardiac disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Nodule	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Presyncope	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Pyrexia	General disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected6 at risk EG0020 events0 affected2 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Viral infection	Infections and infestations	MedDRA 22.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003
Vitamin D deficiency	Metabolism and nutrition disorders	MedDRA 22.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003

ID	Term
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D015229	Sexually Transmitted Diseases, Viral
D012749	Sexually Transmitted Diseases
D016180	Lentivirus Infections
D012192	Retroviridae Infections
D012327	RNA Virus Infections
D014777	Virus Diseases
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D007153	Immunologic Deficiency Syndromes
D007154	Immune System Diseases

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anal abscess	Infections and infestations	MedDRA 22.1	Systematic Assessment		EG0000 events0 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG0030 events0 affected6 at risk EG0040 events0 affected6 at risk EG0051 events1 affected6 at risk EG0060 events0 affected2 at risk
Congestive cardiomyopathy	Cardiac disorders	MedDRA 22.1	Systematic Assessment		EG0001 events1 affected6 at risk EG0010 events0 affected6 at risk EG0020 events0 affected2 at risk EG003