A Two-part Study to Compare a Tablet and Capsule Formulation of GSK2838232 With and Without Food, and to Assess the Safety and Drug Levels of Repeated Once-daily Doses of GSK2838232 Without Ritonavir

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT03234036

Collaborator

(none)

Enrollment

Location

Arms

3.3

Actual Duration (Months)

7.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will be conducted in two Parts to confirm the acceptability/selection of a tablet formulation for future clinical development of GSK2838232. Part 1 of the study will assess single ritonavir (RTV)-boosted doses of a new tablet formulation given with food (containing approximately 30% fat) against the reference capsule formulation also given with food and then will assess the impact of fasted conditions on the tablet performance. In Part 2, non-boosted GSK2838232 will be given as once-daily tablet doses for 11 days in a separate group of subjects, assuming the tablet performance is considered acceptable from Part 1. Approximately 16 healthy subjects will be enrolled to provide at least 12 evaluable subjects through the three study periods in Part 1. 10 healthy subjects will be enrolled to provide at least 8 evaluable subjects through the single study period in Part 2. The maximum duration of study participation will be approximately 9 to 10 weeks for Part 1; and 8 to 9 weeks for Part 2.

Condition or Disease	Intervention/Treatment	Phase
Infection, Human Immunodeficiency Virus HIV Infections	Drug: GSK2838232 100 mg tablet Drug: GSK2838232 50 mg capsule Drug: Ritonavir 100 mg tablets Drug: Placebo for GSK2838232 tablets	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

26 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

The randomization number will determine the allocation of treatment sequences (ABC or BAC) for Part 1, and of treatment (GSK2838232 without RTV or placebo) for Part 2. Allocation to treatment for Part 1A or Part 1B (with Part 2 being fixed) will be according to a predetermined random order.The randomization number will determine the allocation of treatment sequences (ABC or BAC) for Part 1, and of treatment (GSK2838232 without RTV or placebo) for Part 2. Allocation to treatment for Part 1A or Part 1B (with Part 2 being fixed) will be according to a predetermined random order.

Masking:

Double (Participant, Investigator)

Masking Description:

Part 1 of the study will be open label and thus not be blinded. Part 2 of the study will be single blinded because of the unavailability of matching placebo tablets. The Principal Investigator and the subject will be completely blinded to specific treatment assignment.

Primary Purpose:

Treatment

Official Title:

A Two Part Study to Assess i) the Relative Bioavailability and Food Effect of a Novel Tablet Formulation of Boosted-GSK2838232 Compared to Capsule and ii) the Safety and Pharmacokinetics of Repeated Once-Daily Doses of Non-boosted GSK2838232

Actual Study Start Date :

Aug 2, 2017

Actual Primary Completion Date :

Nov 10, 2017

Actual Study Completion Date :

Nov 10, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment sequence ABC: Part 1 A single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation will be administered under fed conditions (treatment A) in period 1 in Part 1A. A single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation will be administered under fed conditions (treatment B) in period 2 in Part 1A. Both these treatments in Part 1A will be administered with RTV in fed state with a washout of 10 days. A single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation (with RTV) will be administered under fasted conditions (treatment C) in period 3 in Part 1B. There will be a wash out of 15 days between Part 1A and Part 1B.	Drug: GSK2838232 100 mg tablet It is a white to slightly colored tablet. It will be supplied as prefilled tablets in bulk for dispensing to subjects at the site according to the treatment code. Drug: GSK2838232 50 mg capsule It is a pink unmarked capsule. It will be supplied as prefilled capsules in bulk for dispensing to subjects at the site according to the treatment code. Drug: Ritonavir 100 mg tablets It is a white film-coated ovaloid tablets.
Experimental: Treatment sequence BAC: Part 1 A single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation will be administered under fed conditions (treatment B) in period 1 in Part 1A. A single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation will be administered under fed conditions (treatment A) in period 2 in Part 1A. A single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation (with RTV) will be administered under fasted conditions (treatment C) in period 3 in Part 1B. There will be a wash out of 15 days between Part 1A and Part 1B.	Drug: GSK2838232 100 mg tablet It is a white to slightly colored tablet. It will be supplied as prefilled tablets in bulk for dispensing to subjects at the site according to the treatment code. Drug: GSK2838232 50 mg capsule It is a pink unmarked capsule. It will be supplied as prefilled capsules in bulk for dispensing to subjects at the site according to the treatment code. Drug: Ritonavir 100 mg tablets It is a white film-coated ovaloid tablets.
Experimental: GSK2838232 tablet without RTV: Part 2 In Part 2, subjects will receive non-RTV boosted GSK2838232 500 mg, given as single daily doses for 11 days. The dose will not exceed 500 mg (as 5 x 100 mg tablets) once daily (QD).	Drug: GSK2838232 100 mg tablet It is a white to slightly colored tablet. It will be supplied as prefilled tablets in bulk for dispensing to subjects at the site according to the treatment code.
Placebo Comparator: Placebo without RTV: Part 2 In Part 2, subjects will receive a Placebo given as single daily doses for 11 days.	Drug: Placebo for GSK2838232 tablets It is a white to slightly colored tablet. The placebo tablets supplied will not be identical to GSK2838232 tablets. It will be administered by site staff via an opaque card or paper tube.

Outcome Measures

Primary Outcome Measures

Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1 and 2 of Part 1]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet and capsule formulation in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods. Pharmacokinetic Population comprised of all participants in the Safety Population who had at least 1 non-missing pharmacokinetic assessment (Non-quantifiable [NQ] values were considered as non-missing values).
Part 1: Maximum Observed Concentration (Cmax) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1 and 2 of Part 1]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet and capsule formulation in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: AUC (0-infinity) Following Administration of GSK2838232 Tablet in Fasted and Fed State [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet formulation in fed and fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Cmax Following Administration of GSK2838232 Tablet in Fasted and Fed State [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet formulation in fed and fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Time of Occurrence of Cmax (Tmax) Following Administration of GSK2838232 Tablet in Fasted and Fed State [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet formulation in fed and fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs [Up to 25 days]
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. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/ birth defect, is associated with liver injury or impaired liver function or any other situations as per medical or scientific judgment. Safety Population comprised of all participants who received at least 1 dose of the study treatment (including placebo) with at least 1 post-Baseline safety assessment. Number of participants with SAEs and common non-SAEs (>=5%) are presented.
Part 2: Number of Participants With Worst Case Hematology Results to Potential Clinical Importance (PCI) Criteria [Up to 25 days]
Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. PCI ranges were < 0.075 or >0.54 proportion of red blood cells in blood for hematocrit, <25 or >180 grams per liter (g/L) for hemoglobin, < 3 or >20 cells per liter (cells/L) for leukocytes, 0.8 x10^9 cells/L for lymphocytes, 1.5 x10^9 cells/L for neutrophils, and <100 or >550 cells/L for platelets. Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (example given [e.g.], High to High), or whose value became within range, were recorded in the "To within Range or No Change" category.
Part 2: Number of Participants With Worst Case Clinical Chemistry Results to PCI Criteria [Up to 25 days]
Blood samples were collected from participants for analysis of following clinical chemistry parameters; glucose, alanine aminotransferase (ALT), albumin, alkaline phosphatase, aspartate aminotransferase (AST), bilirubin, calcium, potassium and sodium. PCI ranges were <30 g/L for albumin, <2 or >2.75 millimoles per liter (mmol/L) for calcium, <3 or >9 mmol/L for glucose, >=2 times Upper limit of Normal (ULN) units per liter (U/L) for ALT, >=2 times ULN U/L for alkaline phosphatase, >=2 times ULN U/L for AST, >=1.5 times ULN micromoles per liter (µmol/L) for bilirubin, <3 or >5.5 mmol/L for potassium, and <130 or >150 mmol/L for sodium. Participants were counted in the worst case category that their value changes to (low, within range or no change,or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category.
Part 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria [Up to 25 days]
Urine samples were collected from participants for analysis of following urinalysis parameters; specific gravity, potential of hydrogen (pH), presence of glucose, protein, occult blood, ketones in urine analyzed by dipstick method. The dipstick test gives results in a semi-quantitative manner. 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. The reference range is 1.002-1.030. Urine pH is an acid-base measurement. Normal urine has a slightly acid pH (5.0 - 6.0). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the "To Normal or No Change" category.
Part 2: Blood Pressure at Indicated Time Points [Day -1; Pre-dose, 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)]
Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in supine position after 10 minutes rest for the participants at indicated time points.
Part 2: Change From Baseline in Blood Pressure [Baseline (Day -1) and 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)]
SBP and DBP were measured in supine position after 10 minutes rest for participants at indicated time points. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Part 2: Pulse Rate at Indicated Time Points [Day -1; Pre-dose, 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)]
Pulse rate of participants was measured in supine position after 10 minutes rest at indicated time points.
Part 2: Change From Baseline in Pulse Rate [Baseline (Day -1) and 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)]
Pulse rate was measured in supine position after 10 minutes rest at indicated time points. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Part 2: Number of Participants With Abnormal Electrocardiogram (ECG) Findings [Day -1; 1, 4, 12 hours on Day 1; Days 2, 3, 5, 8; 1, 4, 12, 24 Hours on Day 11; Follow-up (Day 25)]
Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Part 2: Change From Baseline in Mean Heart Rate Values as ECG Parameter [Baseline (Day -1) and 1, 4, 12 hours on Day 1; Days 2, 3 5, 8; Pre-dose, 1, 4, 12, 24 hours Day 11; Follow-up (Day 25)]
Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Part 2: Change From Baseline in PR Interval, QRS, QT Interval, and QTcF Interval as ECG Parameters [Baseline (Day -1) and 1, 4, 12 hours on Day 1; Days 2, 3 5, 8; Pre-dose, 1, 4, 12, 24 hours Day 11; Follow-up (Day 25)]
Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates measures PR, QRS, QT and QTcF intervals. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Part 2: 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 Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State [Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Cmax Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State [Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Observed Concentration at the End of the Dosing Interval (Ctau) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State [Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Tmax Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State [Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Lag-time (Tlag) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 1 [Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1 in Part 2]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Tlag is a time delay between drug administration and first observed concentration. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: AUC(0-infinity) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11 [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Apparent Terminal Phase Half-life (T1/2) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11 [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Time of Last Quantifiable Concentration (Tlast) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11 [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Secondary Outcome Measures

Part 1: Number of Participants With SAEs and Non-SAEs [Up to 60 days]
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. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/ birth defect, is associated with liver injury or impaired liver function or any other situations as per medical or scientific judgment. Number of participants with SAEs and common non-SAEs (>=5%) are presented.
Part 1: Number of Participants With Worst Case Hematology Results to PCI Criteria [Up to 60 days]
Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. PCI ranges were >0.54 as proportion of red blood cells in blood for hematocrit, >180 g/L for hemoglobin, < 3 or >20 cells/L for leukocytes, 0.8 x10^9 cells/L for lymphocytes, 1.5 x10^9 cells/L for neutrophils, and <100 or >550 cells/L for platelets. Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category.
Part 1: Number of Participants With Worst Case Clinical Chemistry Results to PCI Criteria [Up to 60 days]
Blood samples were collected from participants for analysis of following clinical chemistry parameters; glucose, ALT, albumin, alkaline phosphatase, AST, bilirubin, calcium, potassium and sodium. PCI ranges were <30 g/L for albumin, <2 or 2.75 mmol/L for calcium, <3 or >9 mmol/L for glucose, >=2 times ULN U/L for ALT, >=2 times ULN U/L for alkaline phosphatase, >=2 times ULN U/L for AST, >=1.5 times ULN µmol/L for bilirubin, <3 or >5.5 mmol/L for potassium, and <130 or >150 mmol/L for sodium. Participants were counted in the worst case category that their value changes to (low, within range or no change,or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category.
Part 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria [Up to 60 days]
Urine samples were collected from participants for analysis of following urinalysis parameters; specific gravity, pH, presence of glucose, protein, occult blood, ketones in urine analyzed by dipstick method. The dipstick test gives results in a semi-quantitative manner. 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. The reference range is 1.002-1.030. Urine pH is an acid-base measurement. Normal urine has a slightly acid pH (5.0 - 6.0). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the "To Normal or No Change" category.
Part 1: Blood Pressure at Indicated Time Points [Day -2; Day -1; Pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1]
SBP and DBP of participants were measured in supine position after 10 minutes rest at indicated time points.
Part 1: Change From Baseline in Blood Pressure [Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1]
SBP and DBP were measured in supine position after 10 minutes rest for the participant at indicated time points. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Part 1: Pulse Rate at Indicated Time Points [Day -2; Day -1; Pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1]
Pulse rate was measured in supine position after 10 minutes rest for the participant at indicated time points.
Part 1: Change From Baseline in Pulse Rate [Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1]
Pulse rate was measured in supine position after 10 minutes rest for the participant at indicated time points. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Part 1: Number of Participants With Abnormal ECG Findings [Day -2, Day -1; 1, 2, 4, 6, 8, , 12, 24, 48, 72 hours on Day 1]
Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTcF intervals. CS and NCS abnormal ECG findings have been presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Part 1: Change From Baseline in Mean Heart Rate Values as ECG Parameter [Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 hours on Day 1]
Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Part 1: Change From Baseline in PR Interval, QRS, QT Interval, and QTcF Interval as ECG Parameters [Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 hours on Day 1]
Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates measures PR, QRS, QT and QTcF intervals. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Part 1: Tlag Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Tlag is a time delay between drug administration and first observed concentration. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Tmax Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: T1/2 Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Tlast Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: Plasma Drug Concentration at 24 Hours (C24) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 1: AUC(0-t) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State [Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1]
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Part 2: Slope of Pre-dose Concentration of GSK2838232 Administered as Non-boosted Once-daily Doses of a Tablet Formulation to Assess Achievement of Steady State [Pre-dose on Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10 and Day 11 in Part 2]
Blood sample were collected at indicated time points to assess pre-dose concentration of GSK2838232 when administered as non-boosted once-daily doses of a tablet formulation for 11 days in Part 2. Slope and 90 percent confidence interval have been presented.
Part 2: Accumulation Ratio Calculated From AUC(0-tau) Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation [Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2]
Blood sample were collected at indicated time points to calculate accumulation ratio from AUC(0-tau) following administration of GSK2838232 as non-boosted once-daily doses of a tablet formulation. Accumulation ratio of GSK2838232 was evaluated by Day 11, AUC (0-tau) divided by Day 1, AUC (0-tau).
Part 2: Accumulation Ratio Calculated From Cmax Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation [Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2]
Blood sample were collected at indicated time points to calculate accumulation ratio from Cmax following administration of GSK2838232 as non-boosted once-daily doses of a tablet formulation. Accumulation ratio of GSK2838232 was evaluated by Day 11, Cmax divided by Day 1, Cmax.
Part 2: Accumulation Ratio Calculated From Ctau Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation [Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2]
Blood sample were collected at indicated time points to calculate accumulation ratio from Ctau following administration of GSK2838232 as non-boosted once-daily doses of a tablet formulation. Accumulation ratio of GSK2838232 was evaluated by Day 11, Ctau divided by Day 1, Ctau.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Between 18 and 55 years of age inclusive, at the time of signing the informed consent.
Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, and outside the reference range for the population being studied, may be included only if the Investigator in consultation with the medical monitor, if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
A creatinine clearance (CLcr) > 80 milliliter per minute (mL/min) as determined by Cockcroft-Gault equation: CLcr = (140 minus age) multiplied by weight divided by (72 multiplied by serum creatinine) (times 0.85 if female) where age is in years, weight in kilogram (kg), and serum creatinine is in units of milligram per deciliter (mg/dL).
Body weight >=50.0 kg (110 pounds [lbs.]) for men and >=45.0 kg (99 lbs) for women and body mass index (BMI) within the range 18.5 to 31.0 kg/meter (m)^2 (inclusive).
Males or females.
A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin [hCG] test), not lactating, and of non-reproductive potential which is defined as:

Reproductive potential:

There is no definitive drug-drug interaction (DDI) information with GSK2838232 and an interaction with oral contraceptives is possible, so other (barrier, inter-uterine device etc.) methods of contraception will be required. Females of reproductive potential may only be enrolled if they are using two forms of complementary contraception, which must include at least one barrier method. They will be counseled on safer sex practices. Fertile females, who have an established, long-term lifestyle of sexual abstinence, or only same sex partners, require no other means of birth control.

Non-reproductive potential:

Pre-menopausal females with one of the following: Documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; hysterectomy; documented Bilateral Oophorectomy.
Postmenopausal defined as 12 months of spontaneous amenorrhea in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT) must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until one week after the last dose of study medication.
Vasectomy with documentation of azoospermia.
Male condom plus partner use of one of the contraceptive options below: Contraceptive subdermal implant with a <1 percent rate of failure per year; intrauterine device or intrauterine system with a <1 percent rate of failure per year; oral contraceptive, either combined or progestogen alone or injectable progestogen; contraceptive vaginal ring; percutaneous contraceptive patches.
Capable of giving signed informed consent.

Exclusion Criteria:

ALT >1.5 times upper limit of normal (ULN)
Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities.
Subjects who have asthma or a history of asthma.
Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GlaxoSmithKline medical monitor, the medication will not interfere with the study procedures or compromise participant safety.
History of regular alcohol consumption (within 6 months prior to screening or unable to refrain from alcohol use from 5 days prior to admission through the last blood sample collected) defined as:

• For United States sites: an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 gram of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.

Regular use of tobacco- or nicotine- containing products within 6 months prior to screening. Unable to refrain from smoking from the Screening Visit through the last blood sample collected. As confirmed by a urine cotinine test.
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.
Presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C virus (HCV) test result at screening or within 3 months prior to first dose of study treatment.
Screening or Baseline cardiac troponin I greater than the 99 percent cutoff (>0.045 nanogram [ng]/mL by the Dimension Vista cTnI assay) for a given assay.
A positive pre-study drug/alcohol screen.
A positive test for human immunodeficiency virus (HIV) antibody.
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
Exclusion Criteria for 24-hour Screening Holter:
Any symptomatic arrhythmia (except isolated extra systoles).
Sustained cardiac arrhythmias (such as atrial fibrillation or flutter, supraventricular tachycardia (>= 10 consecutive beats), complete heart block).
Non-sustained or sustained ventricular tachycardia (defined as >=3 consecutive ventricular ectopic beats).
Any conduction abnormality (including but not specific to left or right incomplete or complete bundle branch block, atrioventricular (AV) block [2nd degree or higher], Wolff Parkinson White (WPW) syndrome etc.).
Sinus Pauses >3 seconds.
300 or more supraventricular ectopic beats in 24 hours.
250 or more ventricular ectopic beats in 24 hours.
Any clinically significant abnormal echocardiogram finding.
Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination):
Heart rate <45 or >100 beats per minute (bpm) for males; <50 or >100 bpm for females
PR interval <120 or >220 milliseconds (msec)
QRS duration <70 or >120 msec
QTc interval (Fridericia's) >450 msec
Evidence of previous myocardial infarction (does not include ST segment changes associated with re-polarization).
Any conduction abnormality (including but not specific to left or right complete bundle branch block, AV block [2nd degree or higher], WPW syndrome).
Sinus Pauses >3 seconds.
Any significant arrhythmia which, in the opinion of the Investigator or GSK medical monitor, will interfere with the safety for the individual subject.
Non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Baltimore	Maryland	United States	21225

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

More Information

Publications

Johnson M, Jewell RC, Gan J, Dumont E, Burns O, Johns BA. A Phase 1 Study to Assess the Relative Bioavailability, Food Effect, and Safety of a Tablet Formulation of GSK2838232, a Novel HIV Maturation Inhibitor in Healthy Participants After Single and Repeated Doses. Clin Pharmacol Drug Dev. 2020 Nov;9(8):972-977. doi: 10.1002/cpdd.820. Epub 2020 Jun 18.

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT03234036

Other Study ID Numbers:

205820

First Posted:

Jul 31, 2017

Last Update Posted:

Oct 28, 2020

Last Verified:

Oct 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

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

Yes

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

Keywords provided by GlaxoSmithKline

Additional relevant MeSH terms:

Infections

Communicable Diseases

HIV Infections

Acquired Immunodeficiency Syndrome

Ritonavir

GSK-2838232

Study Results

Participant Flow

Recruitment Details	This two-part study assessed the relative bioavailability and food effect of a novel tablet formulation of boosted-GSK2838232 compared to capsule along with safety and pharmacokinetics of repeated once-daily doses of non-boosted GSK2838232. This study was conducted at a single center in the United States.
Pre-assignment Detail	Participants received GSK2838232 200 milligrams (mg)/ritonavir as capsule or tablet formulation in Part 1 and GSK2838232 500 mg or placebo in Part 2. A total number of 16 participants were enrolled in Part 1 of the study and 10 participants were enrolled in Part 2. In total, 26 participants were enrolled in the study.

Arm/Group Title	GSK2838232 Capsule Fed/Tablet Fed/Tablet Fasted With Ritonavir	GSK2838232 Tablet Fed/Capsule Fed/Tablet Fasted With Ritonavir	Part 2: Placebo	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule administered under fed conditions in treatment period 1 along with ritonavir 100 mg tablet to be taken with water in fed condition, followed by a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet administered under fed conditions in treatment period 2 along with ritonavir 100 mg tablet to be taken with water in fed condition, followed by a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet administered under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition. Treatment period 1 and 2 were separated by a wash-out period of 10 days. Treatment period 2 and 3 were separated by 15 days wash-out period.	Eligible participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet administered under fed conditions in treatment period 1 along with ritonavir 100 mg tablet to be taken with water in fed condition, followed by a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule administered under fed conditions in treatment period 2 along with ritonavir 100 mg tablet to be taken with water in fed condition, followed by a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet administered under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition. Treatment period 1 and 2 were separated by a wash-out period of 10 days. Treatment period 2 and 3 were separated by 15 days wash-out period.	Eligible participants received single daily doses of placebo tablet orally along with water in fed condition for 11 days.	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Period Title: Part 1: Treatment Period 1(Up to 7 Days)
STARTED	8	8	0	0
COMPLETED	8	8	0	0
NOT COMPLETED	0	0	0	0
Period Title: Part 1: Treatment Period 1(Up to 7 Days)
STARTED	8	8	0	0
COMPLETED	7	7	0	0
NOT COMPLETED	1	1	0	0
Period Title: Part 1: Treatment Period 1(Up to 7 Days)
STARTED	7	7	0	0
COMPLETED	7	7	0	0
NOT COMPLETED	0	0	0	0
Period Title: Part 1: Treatment Period 1(Up to 7 Days)
STARTED	7	7	0	0
COMPLETED	7	7	0	0
NOT COMPLETED	0	0	0	0
Period Title: Part 1: Treatment Period 1(Up to 7 Days)
STARTED	7	7	0	0
COMPLETED	7	7	0	0
NOT COMPLETED	0	0	0	0
Period Title: Part 1: Treatment Period 1(Up to 7 Days)
STARTED	0	0	3	7
COMPLETED	0	0	3	7
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Part 1: All Participants Receiving GSK2838232/Ritonavir	Part 2: Placebo	Part 2: GSK2838232 500 mg Tablet Fed	Total
Arm/Group Description	Eligible participants were assigned to treatment sequence AB or BA where A=single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule under fed condition and B=single dose of GSK2838232 200 mg (as 4 x 50 mg) tablet formulations administered under fed condition in treatment periods 1 and 2 along with ritonavir 100 mg to be taken with water in fed condition. Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet administered under fasted conditions in treatment period 3 along with ritonavir 100 mg to be taken with water in fasted condition. Treatment periods 1 and 2 were separated by a wash-out period of 10 days. Treatment periods 2 and 3 were separated by a wash-out period of 15 days.	Eligible participants received single daily doses of placebo tablet orally along with water in fed condition for 11 days.	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.	Total of all reporting groups
Overall Participants	16	3	7	26
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	36.3 (9.54)	41.0 (9.64)	34.6 (7.81)	36.38 (9.30)
Sex: Female, Male (Count of Participants)
Female	9 56.3%	0 0%	1 14.3%	10 38.5%
Male	7 43.8%	3 100%	6 85.7%	16 61.5%
Race/Ethnicity, Customized (Count of Participants)
BLACK OR AFRICAN AMERICAN	8 50%	2 66.7%	6 85.7%	16 61.5%
WHITE - WHITE/CAUCASIAN/EUROPEAN HERITAGE	6 37.5%	1 33.3%	0 0%	7 26.9%
MULTIPLE-ASIAN & BLACK OR AFRICAN AMERICAN	2 12.5%	0 0%	0 0%	2 7.7%
AMERICAN INDIAN OR ALASKA NATIVE	0 0%	0 0%	1 14.3%	1 3.8%

Outcome Measures

1. Primary Outcome

Title	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet and capsule formulation in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods. Pharmacokinetic Population comprised of all participants in the Safety Population who had at least 1 non-missing pharmacokinetic assessment (Non-quantifiable [NQ] values were considered as non-missing values).
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1 and 2 of Part 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.
Measure Participants	15	15
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanogram per milliliter]	4672.28 (40.68)	4437.98 (30.83)

2. Primary Outcome

Title	Part 1: Maximum Observed Concentration (Cmax) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet and capsule formulation in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1 and 2 of Part 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.
Measure Participants	15	15
Geometric Mean (Geometric Coefficient of Variation) [Nanograms per milliliter]	109.054 (48.01)	118.118 (27.59)

3. Primary Outcome

Title	Part 1: AUC (0-infinity) Following Administration of GSK2838232 Tablet in Fasted and Fed State
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet formulation in fed and fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation administered under fed conditions in treatment periods 1 and 2 along with ritonavir 100 mg tablet to be taken with water in fed condition.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	14
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanogram per milliliter]	4437.98 (30.83)	1816.27 (36.42)

4. Primary Outcome

Title	Part 1: Cmax Following Administration of GSK2838232 Tablet in Fasted and Fed State
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet formulation in fed and fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation administered under fed conditions in treatment periods 1 and 2 along with ritonavir 100 mg tablet to be taken with water in fed condition.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	14
Geometric Mean (Geometric Coefficient of Variation) [Nanograms per milliliter]	118.118 (27.59)	50.437 (35.61)

5. Primary Outcome

Title	Part 1: Time of Occurrence of Cmax (Tmax) Following Administration of GSK2838232 Tablet in Fasted and Fed State
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet formulation in fed and fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation administered under fed conditions in treatment periods 1 and 2 along with ritonavir 100 mg tablet to be taken with water in fed condition.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	14
Median (Full Range) [Hours]	5.983	3.508

6. Primary Outcome

Title	Part 2: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs
Description	An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/ birth defect, is associated with liver injury or impaired liver function or any other situations as per medical or scientific judgment. Safety Population comprised of all participants who received at least 1 dose of the study treatment (including placebo) with at least 1 post-Baseline safety assessment. Number of participants with SAEs and common non-SAEs (>=5%) are presented.
Time Frame	Up to 25 days

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Part 2: Placebo	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received single daily doses of placebo tablet orally along with water in fed condition for 11 days.	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	3	7
Any SAE	0 0%	0 0%
Any non-SAE	1 6.3%	0 0%

7. Primary Outcome

Title	Part 2: Number of Participants With Worst Case Hematology Results to Potential Clinical Importance (PCI) Criteria
Description	Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. PCI ranges were < 0.075 or >0.54 proportion of red blood cells in blood for hematocrit, <25 or >180 grams per liter (g/L) for hemoglobin, < 3 or >20 cells per liter (cells/L) for leukocytes, 0.8 x10^9 cells/L for lymphocytes, 1.5 x10^9 cells/L for neutrophils, and <100 or >550 cells/L for platelets. Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (example given [e.g.], High to High), or whose value became within range, were recorded in the "To within Range or No Change" category.
Time Frame	Up to 25 days

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Part 2: Placebo	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received single daily doses of placebo tablet orally along with water in fed condition for 11 days.	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	3	7
Hematocrit; To Low	0 0%	0 0%
Hematocrit; To within Range or No Change	3 18.8%	7 233.3%
Hematocrit; To High	0 0%	0 0%
Hemoglobin; To Low	0 0%	0 0%
Hemoglobin; To within Range or No Change	3 18.8%	7 233.3%
Hemoglobin; To High	0 0%	0 0%
Leukocytes; To Low	0 0%	0 0%
Leukocytes; To within Range or No Change	3 18.8%	7 233.3%
Leukocytes; To High	0 0%	0 0%
Lymphocytes; To Low	0 0%	0 0%
Lymphocytes; To within Range or No Change	3 18.8%	7 233.3%
Lymphocytes; To High	0 0%	0 0%
Neutrophils; To Low	1 6.3%	1 33.3%
Neutrophils; To within Range or No Change	2 12.5%	6 200%
Neutrophils; To High	0 0%	0 0%
Platelets; To Low	0 0%	0 0%
Platelets; To within Range or No Change	3 18.8%	7 233.3%
Platelets; To High	0 0%	0 0%

8. Primary Outcome

Title	Part 2: Number of Participants With Worst Case Clinical Chemistry Results to PCI Criteria
Description	Blood samples were collected from participants for analysis of following clinical chemistry parameters; glucose, alanine aminotransferase (ALT), albumin, alkaline phosphatase, aspartate aminotransferase (AST), bilirubin, calcium, potassium and sodium. PCI ranges were <30 g/L for albumin, <2 or >2.75 millimoles per liter (mmol/L) for calcium, <3 or >9 mmol/L for glucose, >=2 times Upper limit of Normal (ULN) units per liter (U/L) for ALT, >=2 times ULN U/L for alkaline phosphatase, >=2 times ULN U/L for AST, >=1.5 times ULN micromoles per liter (µmol/L) for bilirubin, <3 or >5.5 mmol/L for potassium, and <130 or >150 mmol/L for sodium. Participants were counted in the worst case category that their value changes to (low, within range or no change,or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category.
Time Frame	Up to 25 days

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Part 2: Placebo	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received single daily doses of placebo tablet orally along with water in fed condition for 11 days.	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	3	7
Glucose; To Low	0 0%	0 0%
Glucose; To within Range or No Change	3 18.8%	7 233.3%
Glucose; To High	0 0%	0 0%
ALT; To Low	0 0%	0 0%
ALT; To within Range or No Change	3 18.8%	7 233.3%
ALT; To High	0 0%	0 0%
Albumin; To Low	0 0%	0 0%
Albumin; To within Range or No Change	3 18.8%	7 233.3%
Albumin; To High	0 0%	0 0%
Alkaline phosphatase; To Low	0 0%	0 0%
Alkaline phosphatase; To within Range or No Change	3 18.8%	7 233.3%
Alkaline phosphatase; To High	0 0%	0 0%
AST; To Low	0 0%	0 0%
AST; To within Range or No Change	3 18.8%	7 233.3%
AST; To High	0 0%	0 0%
Bilirubin; To Low	0 0%	0 0%
Bilirubin; To within Range or No Change	3 18.8%	7 233.3%
Bilirubin; To High	0 0%	0 0%
Calcium; To Low	0 0%	0 0%
Calcium; To within Range or No Change	3 18.8%	7 233.3%
Calcium; To High	0 0%	0 0%
Potassium; To Low	0 0%	0 0%
Potassium; To within Range or No Change	3 18.8%	7 233.3%
Potassium; To High	0 0%	0 0%
Sodium; To Low	0 0%	0 0%
Sodium; To within Range or No Change	3 18.8%	7 233.3%
Sodium; To High	0 0%	0 0%

9. Primary Outcome

Title	Part 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria
Description	Urine samples were collected from participants for analysis of following urinalysis parameters; specific gravity, potential of hydrogen (pH), presence of glucose, protein, occult blood, ketones in urine analyzed by dipstick method. The dipstick test gives results in a semi-quantitative manner. 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. The reference range is 1.002-1.030. Urine pH is an acid-base measurement. Normal urine has a slightly acid pH (5.0 - 6.0). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the "To Normal or No Change" category.
Time Frame	Up to 25 days

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Part 2: Placebo	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received single daily doses of placebo tablet orally along with water in fed condition for 11 days.	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	3	7
Glucose; To Low	0 0%	0 0%
Glucose; To Normal or No Change	3 18.8%	7 233.3%
Glucose; To High	0 0%	0 0%
Glucose; To Abnormal	0 0%	0 0%
Ketones; To Low	0 0%	0 0%
Ketones; To Normal or No Change	3 18.8%	7 233.3%
Ketones; To High	0 0%	0 0%
Ketones; To Abnormal	0 0%	0 0%
Occult blood; To Low	0 0%	0 0%
Occult blood; To Normal or No Change	2 12.5%	6 200%
Occult blood; To High	0 0%	0 0%
Occult blood; To Abnormal	1 6.3%	1 33.3%
Protein; To Low	0 0%	0 0%
Protein; To Normal or No Change	3 18.8%	7 233.3%
Protein; To High	0 0%	0 0%
Protein; To Abnormal	0 0%	0 0%
Specific gravity; To Low	1 6.3%	0 0%
Specific gravity; To Normal or No Change	2 12.5%	7 233.3%
Specific gravity; To High	0 0%	0 0%
Specific gravity; To Abnormal	0 0%	0 0%
Urine pH; To Low	0 0%	0 0%
Urine pH; To Normal or No Change	3 18.8%	7 233.3%
Urine pH; To High	0 0%	0 0%
Urine pH; To Abnormal	0 0%	0 0%

10. Primary Outcome

Title	Part 2: Blood Pressure at Indicated Time Points
Description	Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in supine position after 10 minutes rest for the participants at indicated time points.
Time Frame	Day -1; Pre-dose, 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Part 2: Placebo	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received single daily doses of placebo tablet orally along with water in fed condition for 11 days.	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	3	7
DBP; DAY -1	73.667 (7.5056)	73.143 (4.7759)
DBP; DAY 1, PREDOSE	65.443 (2.6925)	72.333 (8.1636)
DBP; DAY 1, 1 Hour	54.667 (3.7859)	64.714 (5.8228)
DBP; DAY 1, 4 Hours	62.000 (1.0000)	63.714 (6.7507)
DBP; DAY 2, 24 Hours	73.667 (4.0415)	73.714 (6.0474)
DBP; DAY 3, 48 Hours	66.000 (1.7321)	68.000 (7.3485)
DBP; DAY 4, 72 Hours	69.000 (2.6458)	65.143 (8.3552)
DBP; DAY 5	62.333 (4.9329)	65.000 (7.3258)
DBP; DAY 6	62.667 (4.5092)	66.143 (6.6690)
DBP; DAY 7	64.333 (3.0551)	67.286 (4.8892)
DBP; DAY 8	66.000 (2.6458)	69.286 (6.3957)
DBP; DAY 9	69.000 (4.0000)	66.714 (5.0568)
DBP; DAY 10	65.000 (7.2111)	66.571 (8.0593)
DBP; DAY 11, PREDOSE	65.333 (5.1316)	67.000 (8.0179)
DBP; DAY 11, 1 Hour	62.667 (7.3711)	66.571 (7.6563)
DBP; DAY 11, 4 Hours	63.333 (4.5092)	65.571 (8.5021)
DBP; DAY 11, 24 Hours	67.667 (4.5092)	64.714 (7.0643)
DBP; DAY 11, 48 Hours	66.000 (5.5678)	68.000 (8.9815)
DBP; DAY 11, 72 Hours	66.333 (3.7859)	65.000 (5.8878)
DBP; Follow-Up (DAY 25)	71.000 (1.0000)	76.143 (10.5424)
SBP; DAY -1	121.000 (4.5826)	123.000 (7.3258)
SBP; DAY 1, PREDOSE	107.553 (4.1400)	121.190 (10.8374)
SBP; DAY 1, 1 Hour	99.333 (2.0817)	113.000 (8.7178)
SBP; DAY 1, 4 Hours	105.000 (8.1854)	106.286 (9.6214)
SBP; DAY 2, 24 Hours	110.667 (7.7675)	113.286 (5.0568)
SBP; DAY 3, 48 Hours	111.333 (2.3094)	111.714 (8.7695)
SBP; DAY 4, 72 Hours	108.333 (7.6376)	109.000 (8.2260)
SBP; DAY 5	105.667 (2.3094)	109.000 (3.0551)
SBP; DAY 6	106.667 (4.7258)	107.857 (9.0079)
SBP; DAY 7	103.333 (1.1547)	112.143 (8.6106)
SBP; DAY 8	105.667 (4.1633)	109.571 (6.2412)
SBP; DAY 9	107.333 (7.2342)	110.143 (8.7069)
SBP; DAY 10	110.000 (4.0000)	106.714 (8.8828)
SBP; DAY 11, PREDOSE	107.113 (3.8626)	110.333 (9.7088)
SBP; DAY 11, 1 Hour	113.000 (3.4641)	111.571 (15.7041)
SBP; DAY 11, 4 Hours	108.667 (6.0277)	109.857 (8.7069)
SBP; DAY 11, 24 Hours	107.333 (13.2035)	105.143 (7.7337)
SBP; DAY 11, 48 Hours	109.667 (8.0829)	109.286 (8.8828)
SBP; DAY 11, 72 Hours	110.333 (2.3094)	110.286 (7.6966)
SBP; Follow-Up (DAY 25)	115.667 (5.8595)	123.714 (10.6413)

11. Primary Outcome

Title	Part 2: Change From Baseline in Blood Pressure
Description	SBP and DBP were measured in supine position after 10 minutes rest for participants at indicated time points. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Time Frame	Baseline (Day -1) and 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Part 2: Placebo	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received single daily doses of placebo tablet orally along with water in fed condition for 11 days.	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	3	7
DBP; DAY 1, 1 Hour	-10.777 (4.6690)	-7.619 (4.9086)
DBP; DAY 1, 4 Hours	-3.443 (3.6851)	-8.619 (9.3099)
DBP; DAY 2, 24 Hours	8.223 (2.5455)	1.381 (5.6866)
DBP; DAY 3, 48 Hours	0.557 (4.3485)	-4.333 (8.5244)
DBP; DAY 4, 72 Hours	3.557 (2.2180)	-7.190 (8.9524)
DBP; DAY 5	-3.110 (2.8366)	-7.333 (10.9039)
DBP; DAY 6	-2.777 (3.7175)	-6.190 (7.8255)
DBP; DAY 7	-1.110 (4.4381)	-5.047 (8.9388)
DBP; DAY 8	0.557 (0.5095)	-3.047 (9.4939)
DBP; DAY 9	3.557 (5.5901)	-5.619 (8.5770)
DBP; DAY 10	-0.443 (5.3488)	-5.761 (10.0756)
DBP; DAY 11, PREDOSE	-0.110 (3.4708)	-5.333 (11.3081)
DBP; DAY 11, 1 Hour	-2.777 (5.3385)	-5.761 (12.2366)
DBP; DAY 11, 4 Hours	-2.110 (3.3729)	-6.761 (10.3364)
DBP; DAY 11, 24 Hours	2.223 (5.9279)	-7.619 (10.1445)
DBP; DAY 11, 48 Hours	0.557 (6.7022)	-4.333 (9.7243)
DBP; DAY 11, 72 Hours	0.890 (4.6224)	-7.333 (9.2678)
DBP; Follow-Up (DAY 25)	5.557 (3.2015)	3.810 (10.1939)
SBP; DAY 1, 1 Hour	-8.220 (3.0060)	-8.190 (10.8776)
SBP; DAY 1, 4 Hours	-2.553 (5.6718)	-14.904 (8.2260)
SBP; DAY 2, 24 Hours	3.113 (5.8232)	-7.904 (8.7636)
SBP; DAY 3, 48 Hours	3.780 (1.8347)	-9.476 (6.2626)
SBP; DAY 4, 72 Hours	0.780 (5.4181)	-12.190 (7.1567)
SBP; DAY 5	-1.887 (3.6851)	-12.190 (11.9632)
SBP; DAY 6	-0.887 (7.0661)	-13.333 (15.5386)
SBP; DAY 7	-4.220 (3.7452)	-9.047 (13.8084)
SBP; DAY 8	-1.887 (5.1225)	-11.619 (11.8726)
SBP; DAY 9	-0.220 (6.1657)	-11.047 (14.9222)
SBP; DAY 10	2.447 (7.8192)	-14.476 (13.8688)
SBP; DAY 11, PREDOSE	-0.440 (4.4381)	-10.857 (13.9763)
SBP; DAY 11, 1 Hour	5.447 (6.6678)	-9.619 (19.6856)
SBP; DAY 11, 4 Hours	1.113 (2.6962)	-11.333 (14.3479)
SBP; DAY 11, 24 Hours	-0.220 (13.2912)	-16.047 (15.2791)
SBP; DAY 11, 48 Hours	2.113 (12.0648)	-11.904 (11.8344)
SBP; DAY 11, 72 Hours	2.780 (1.8347)	-10.904 (13.1590)
SBP; Follow-Up (DAY 25)	8.113 (4.6808)	2.524 (10.1553)

12. Primary Outcome

Title	Part 2: Pulse Rate at Indicated Time Points
Description	Pulse rate of participants was measured in supine position after 10 minutes rest at indicated time points.
Time Frame	Day -1; Pre-dose, 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Part 2: Placebo	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received single daily doses of placebo tablet orally along with water in fed condition for 11 days.	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	3	7
DAY -1	63.667 (12.4231)	64.143 (11.7817)
DAY 1, PREDOSE	63.663 (4.0415)	63.714 (11.3991)
DAY 1, 1 Hour	68.000 (8.5440)	72.286 (7.5214)
DAY 1, 4 Hours	64.667 (3.0551)	66.000 (10.1160)
DAY 2, 24 Hours	57.667 (2.8868)	58.286 (8.7123)
DAY 3, 48 Hours	58.000 (2.6458)	59.429 (7.9762)
DAY 4, 72 Hours	58.667 (1.1547)	58.286 (7.7613)
DAY 5	60.667 (2.5166)	66.429 (10.3900)
DAY 6	62.333 (2.3094)	59.143 (6.2564)
DAY 7	59.333 (3.7859)	63.429 (11.4143)
DAY 8	64.333 (4.0415)	62.000 (8.6795)
DAY 9	61.000 (2.6458)	60.714 (6.9693)
DAY 10	63.667 (3.5119)	60.143 (8.4346)
DAY 11, PREDOSE	61.887 (1.3891)	60.810 (9.3355)
DAY 11, 1 Hour	72.667 (4.7258)	70.143 (7.0102)
DAY 11, 4 Hours	68.000 (5.2915)	68.857 (8.4148)
DAY 11, 24 Hours	67.667 (6.4291)	64.571 (7.3679)
DAY 11, 48 Hours	61.667 (6.5064)	61.714 (4.6085)
DAY 11, 72 Hours	63.000 (2.6458)	60.857 (3.9340)
Follow-Up (DAY 25)	70.667 (8.0829)	63.857 (9.4062)

13. Primary Outcome

Title	Part 2: Change From Baseline in Pulse Rate
Description	Pulse rate was measured in supine position after 10 minutes rest at indicated time points. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Time Frame	Baseline (Day -1) and 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Part 2: Placebo	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received single daily doses of placebo tablet orally along with water in fed condition for 11 days.	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	3	7
DAY 1, 1 Hour	4.337 (11.2398)	8.571 (5.4337)
DAY 1, 4 Hours	1.003 (6.6583)	2.286 (9.4965)
DAY 2, 24 Hours	-5.997 (2.5166)	-5.429 (4.4808)
DAY 3, 48 Hours	-5.663 (4.9329)	-4.286 (5.9568)
DAY 4, 72 Hours	-4.997 (5.1316)	-5.429 (7.0937)
DAY 5	-2.997 (5.6862)	2.714 (11.2383)
DAY 6	-1.330 (4.3589)	-4.571 (9.8771)
DAY 7	-4.330 (1.0000)	-0.286 (12.4265)
DAY 8	0.670 (0.0000)	-1.714 (8.2357)
DAY 9	-2.663 (4.9329)	-3.000 (9.7265)
DAY 10	0.003 (7.5056)	-3.571 (10.5886)
DAY 11, PREDOSE	-1.777 (4.1400)	-2.904 (10.5699)
DAY 11, 1 Hour	9.003 (8.3865)	6.429 (10.3760)
DAY 11, 4 Hours	4.337 (8.5049)	5.143 (10.9028)
DAY 11, 24 Hours	4.003 (6.5064)	0.857 (10.2185)
DAY 11, 48 Hours	-1.997 (9.4516)	-2.000 (9.6686)
DAY 11, 72 Hours	-0.663 (4.0415)	-2.857 (8.7974)
Follow-Up (DAY 25)	7.003 (11.9304)	0.143 (10.7995)

14. Primary Outcome

Title	Part 2: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Description	Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Time Frame	Day -1; 1, 4, 12 hours on Day 1; Days 2, 3, 5, 8; 1, 4, 12, 24 Hours on Day 11; Follow-up (Day 25)

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Part 2: Placebo	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received single daily doses of placebo tablet orally along with water in fed condition for 11 days.	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	3	7
NCS: DAY -1	2 12.5%	6 200%
CS: DAY -1	0 0%	0 0%
NCS: DAY 1, 1 Hour	2 12.5%	4 133.3%
CS: DAY 1, 1 Hour	0 0%	0 0%
NCS: DAY 1, 4 Hours	2 12.5%	6 200%
CS: DAY 1, 4 Hours	0 0%	0 0%
NCS: DAY 1, 12 Hours	3 18.8%	6 200%
CS: DAY 1, 12 Hours	0 0%	0 0%
NCS: DAY 2	2 12.5%	5 166.7%
CS: DAY 2	0 0%	0 0%
NCS: DAY 3	3 18.8%	5 166.7%
CS: DAY 3	0 0%	0 0%
NCS: DAY 5	3 18.8%	6 200%
CS: DAY 5	0 0%	0 0%
NCS: DAY 8	2 12.5%	7 233.3%
CS: DAY 8	0 0%	0 0%
NCS: DAY 11, 1 Hour	2 12.5%	3 100%
CS: DAY 11, 1 Hour	0 0%	0 0%
NCS: DAY 11, 4 Hours	2 12.5%	5 166.7%
CS: DAY 11, 4 Hours	0 0%	0 0%
NCS: DAY 11, 12 Hours	2 12.5%	4 133.3%
CS: DAY 11, 12 Hours	0 0%	0 0%
NCS: DAY 11, 24 Hours	2 12.5%	5 166.7%
CS: DAY 11, 24 Hours	0 0%	0 0%
NCS: Follow-up (DAY 25)	1 6.3%	6 200%
CS: Follow-up (DAY 25)	0 0%	0 0%

15. Primary Outcome

Title	Part 2: Change From Baseline in Mean Heart Rate Values as ECG Parameter
Description	Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Time Frame	Baseline (Day -1) and 1, 4, 12 hours on Day 1; Days 2, 3 5, 8; Pre-dose, 1, 4, 12, 24 hours Day 11; Follow-up (Day 25)

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Part 2: Placebo	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received single daily doses of placebo tablet orally along with water in fed condition for 11 days.	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	3	7
DAY 1, 1 Hour	4.000 (10.1734)	10.240 (5.0930)
DAY 1, 4 Hours	2.000 (5.9287)	1.954 (3.9733)
DAY 1, 12 Hours	-6.000 (6.8912)	0.526 (5.1336)
DAY 2	-8.000 (0.8826)	-5.331 (4.8861)
DAY 3	-5.333 (5.4902)	-1.046 (4.9332)
DAY 5	-3.667 (2.6062)	2.669 (11.9804)
DAY 8	-2.000 (1.8571)	0.954 (5.8978)
DAY 11, PREDOSE	-4.333 (1.7670)	-0.903 (6.9388)
DAY 11, 1 Hour	10.333 (7.7564)	6.383 (5.9634)
DAY 11, 4 Hours	1.000 (4.0986)	4.811 (8.2683)
DAY 11, 12 Hours	-0.667 (3.8461)	-0.189 (5.6490)
DAY 11, 24 Hours	2.667 (4.8106)	0.954 (4.8878)
Follow-up (DAY 25)	2.333 (12.4705)	0.669 (8.2733)

16. Primary Outcome

Title	Part 2: Change From Baseline in PR Interval, QRS, QT Interval, and QTcF Interval as ECG Parameters
Description	Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates measures PR, QRS, QT and QTcF intervals. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Time Frame	Baseline (Day -1) and 1, 4, 12 hours on Day 1; Days 2, 3 5, 8; Pre-dose, 1, 4, 12, 24 hours Day 11; Follow-up (Day 25)

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Part 2: Placebo	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received single daily doses of placebo tablet orally along with water in fed condition for 11 days.	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	3	7
PR interval; DAY 1, 1 Hour	-7.110 (2.0360)	-3.999 (10.6110)
PR interval; DAY 1, 4 Hours	-6.443 (3.7945)	-12.284 (13.9800)
PR interval; DAY 1, 12 Hours	-0.443 (11.9348)	3.430 (5.7511)
PR interval; DAY 2	4.890 (3.6695)	3.716 (5.1471)
PR interval; DAY 3	1.557 (4.2847)	4.573 (6.1252)
PR interval; DAY 5	6.223 (9.1999)	2.287 (9.5818)
PR interval; DAY 8	6.223 (10.8609)	7.430 (11.6897)
PR interval; DAY 11, PREDOSE	5.113 (10.1172)	7.620 (5.5483)
PR interval; DAY 11, 1 Hour	-5.777 (7.3456)	2.287 (5.2749)
PR interval; DAY 11, 4 Hours	-3.110 (10.8418)	-0.570 (9.9657)
PR interval; DAY 11, 12 Hours	4.223 (12.6221)	1.716 (9.4661)
PR interval; DAY 11, 24 Hours	2.890 (10.8418)	3.144 (6.0321)
PR interval; Follow-up (DAY 25)	-10.443 (5.0039)	2.001 (13.1373)
QRS interval; DAY 1, 1 Hour	3.330 (5.2915)	-1.713 (3.3072)
QRS interval; DAY 1, 4 Hours	1.997 (4.6188)	-1.713 (1.4322)
QRS interval; DAY 1, 12 Hours	6.663 (4.6188)	1.716 (3.6295)
QRS interval; DAY 2	1.330 (2.0000)	0.287 (2.2711)
QRS interval; DAY 3	2.663 (3.0551)	-4.570 (5.8288)
QRS interval; DAY 5	3.997 (4.1633)	-1.999 (2.8532)
QRS interval; DAY 8	-0.003 (1.1547)	-3.141 (4.1578)
QRS interval; DAY 11, PREDOSE	1.107 (4.3393)	-0.570 (1.9401)
QRS interval; DAY 11, 1 Hour	-0.003 (2.3094)	-0.856 (5.1594)
QRS interval; DAY 11, 4 Hours	-1.337 (1.1547)	-2.570 (3.0890)
QRS interval; DAY 11, 12 Hours	3.330 (3.4641)	-0.856 (4.4676)
QRS interval; DAY 11, 24 Hours	-1.337 (1.1547)	-0.570 (3.7401)
QRS interval; Follow-up (DAY 25)	1.997 (11.0151)	1.716 (1.5811)
QT interval; DAY 1, 1 Hour	-8.223 (18.0177)	-26.094 (12.8322)
QT interval; DAY 1, 4 Hours	-3.557 (9.7159)	-11.523 (11.6047)
QT interval; DAY 1, 12 Hours	18.443 (18.0654)	-7.237 (15.5856)
QT interval; DAY 2	5.777 (4.0741)	0.763 (9.3458)
QT interval; DAY 3	5.777 (18.7403)	-8.951 (11.9189)
QT interval; DAY 5	-0.890 (8.9502)	-10.666 (19.1883)
QT interval; DAY 8	1.110 (2.3378)	-8.951 (14.2945)
QT interval; DAY 11, PREDOSE	5.553 (6.1963)	-4.283 (13.7560)
QT interval; DAY 11, 1 Hour	-18.223 (12.2979)	-28.380 (19.3087)
QT interval; DAY 11, 4 Hours	-8.223 (10.0299)	-20.380 (17.7740)
QT interval; DAY 11, 12 Hours	5.777 (10.5451)	-13.237 (13.1751)
QT interval; DAY 11, 24 Hours	-10.890 (12.6010)	-13.523 (11.7381)
QT interval; Follow-up (DAY 25)	0.443 (26.9777)	-3.237 (20.6284)
QTcF interval; DAY 1, 1 Hour	-0.667 (6.3366)	-5.857 (10.3146)
QTcF interval; DAY 1, 4 Hours	1.000 (2.1838)	-7.429 (7.1165)
QTcF interval; DAY 1, 12 Hours	7.000 (8.2158)	-6.286 (10.9182)
QTcF interval; DAY 2	-10.667 (4.6671)	-10.143 (6.7366)
QTcF interval; DAY 3	-5.000 (7.6908)	-10.714 (9.6264)
QTcF interval; DAY 5	-7.667 (4.1800)	-6.286 (7.6605)
QTcF interval; DAY 8	-2.000 (2.0246)	-6.714 (6.5305)
QTcF interval; DAY 11, PREDOSE	-2.887 (2.9150)	-6.476 (5.7033)
QTcF interval; DAY 11, 1 Hour	1.000 (4.8434)	-15.286 (11.1814)
QTcF interval; DAY 11, 4 Hours	-5.667 (6.1719)	-11.000 (4.8767)
QTcF interval; DAY 11, 12 Hours	5.333 (3.8474)	-12.571 (7.6845)
QTcF interval; DAY 11, 24 Hours	-5.667 (2.9652)	-10.429 (7.7286)
QTcF interval; Follow-up (DAY 25)	4.000 (5.8145)	-2.571 (12.9581)

17. Primary Outcome

Title	Part 2: 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 Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time Frame	Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	7
Day 1	895.42 (39.08)
Day 11	1184.55 (35.34)

18. Primary Outcome

Title	Part 2: Cmax Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time Frame	Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	7
Day 1	79.575 (45.69)
Day 11	94.239 (34.24)

19. Primary Outcome

Title	Part 2: Observed Concentration at the End of the Dosing Interval (Ctau) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time Frame	Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	7
Day 1	21.620 (42.51)
Day 11	27.668 (41.16)

20. Primary Outcome

Title	Part 2: Tmax Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time Frame	Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	7
Day 1	4.000
Day 11	3.500

21. Primary Outcome

Title	Part 2: Lag-time (Tlag) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 1
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Tlag is a time delay between drug administration and first observed concentration. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time Frame	Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1 in Part 2

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	7
Median (Full Range) [Hours]	0.500

22. Primary Outcome

Title	Part 2: AUC(0-infinity) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	7
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanograms per milliliter]	1816.34 (37.32)

23. Primary Outcome

Title	Part 2: Apparent Terminal Phase Half-life (T1/2) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	7
Geometric Mean (Geometric Coefficient of Variation) [Hours]	23.217 (37.85)

24. Primary Outcome

Title	Part 2: Time of Last Quantifiable Concentration (Tlast) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	7
Median (Full Range) [Hours]	118.800

25. Secondary Outcome

Title	Part 1: Number of Participants With SAEs and Non-SAEs
Description	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/ birth defect, is associated with liver injury or impaired liver function or any other situations as per medical or scientific judgment. Number of participants with SAEs and common non-SAEs (>=5%) are presented.
Time Frame	Up to 60 days

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	15	14
Any SAE	0 0%	0 0%	0 0%
Any non-SAE	3 18.8%	2 66.7%	1 14.3%

26. Secondary Outcome

Title	Part 1: Number of Participants With Worst Case Hematology Results to PCI Criteria
Description	Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. PCI ranges were >0.54 as proportion of red blood cells in blood for hematocrit, >180 g/L for hemoglobin, < 3 or >20 cells/L for leukocytes, 0.8 x10^9 cells/L for lymphocytes, 1.5 x10^9 cells/L for neutrophils, and <100 or >550 cells/L for platelets. Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category.
Time Frame	Up to 60 days

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	15	14
Hematocrit; To Low	0 0%	0 0%	0 0%
Hematocrit; To within Range or No Change	15 93.8%	15 500%	14 200%
Hematocrit; To High	0 0%	0 0%	0 0%
Hemoglobin; To Low	0 0%	0 0%	0 0%
Hemoglobin; To within Range or No Change	15 93.8%	15 500%	14 200%
Hemoglobin; To High	0 0%	0 0%	0 0%
Leukocytes; To Low	0 0%	0 0%	0 0%
Leukocytes; To within Range or No Change	15 93.8%	15 500%	14 200%
Leukocytes; To High	0 0%	0 0%	0 0%
Lymphocytes; To Low	0 0%	0 0%	0 0%
Lymphocytes; To within Range or No Change	15 93.8%	15 500%	14 200%
Lymphocytes; To High	0 0%	0 0%	0 0%
Neutrophils; To Low	0 0%	0 0%	0 0%
Neutrophils; To within Range or No Change	15 93.8%	15 500%	14 200%
Neutrophils; To High	0 0%	0 0%	0 0%
Platelets; To Low	0 0%	0 0%	0 0%
Platelets; To within Range or No Change	15 93.8%	15 500%	14 200%
Platelets; To High	0 0%	0 0%	0 0%

27. Secondary Outcome

Title	Part 1: Number of Participants With Worst Case Clinical Chemistry Results to PCI Criteria
Description	Blood samples were collected from participants for analysis of following clinical chemistry parameters; glucose, ALT, albumin, alkaline phosphatase, AST, bilirubin, calcium, potassium and sodium. PCI ranges were <30 g/L for albumin, <2 or 2.75 mmol/L for calcium, <3 or >9 mmol/L for glucose, >=2 times ULN U/L for ALT, >=2 times ULN U/L for alkaline phosphatase, >=2 times ULN U/L for AST, >=1.5 times ULN µmol/L for bilirubin, <3 or >5.5 mmol/L for potassium, and <130 or >150 mmol/L for sodium. Participants were counted in the worst case category that their value changes to (low, within range or no change,or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category.
Time Frame	Up to 60 days

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	15	14
Glucose; To Low	0 0%	0 0%	0 0%
Glucose; To within Range or No Change	15 93.8%	15 500%	14 200%
Glucose; To High	0 0%	0 0%	0 0%
ALT; To Low	0 0%	0 0%	0 0%
ALT; To within Range or No Change	15 93.8%	15 500%	14 200%
ALT; To High	0 0%	0 0%	0 0%
Albumin; To Low	0 0%	0 0%	0 0%
Albumin; To within Range or No Change	15 93.8%	15 500%	14 200%
Albumin; To High	0 0%	0 0%	0 0%
Alkaline phosphatase; To Low	0 0%	0 0%	0 0%
Alkaline phosphatase; To within Range or No Change	15 93.8%	15 500%	14 200%
Alkaline phosphatase; To High	0 0%	0 0%	0 0%
AST; To Low	0 0%	0 0%	0 0%
AST; To within Range or No Change	15 93.8%	15 500%	14 200%
AST; To High	0 0%	0 0%	0 0%
Bilirubin; To Low	0 0%	0 0%	0 0%
Bilirubin; To within Range or No Change	15 93.8%	15 500%	14 200%
Bilirubin; To High	0 0%	0 0%	0 0%
Calcium; To Low	0 0%	0 0%	0 0%
Calcium; To within Range or No Change	15 93.8%	15 500%	14 200%
Calcium; To High	0 0%	0 0%	0 0%
Potassium; To Low	0 0%	0 0%	0 0%
Potassium; To within Range or No Change	15 93.8%	15 500%	14 200%
Potassium; To High	0 0%	0 0%	0 0%
Sodium; To Low	0 0%	0 0%	0 0%
Sodium; To within Range or No Change	15 93.8%	15 500%	14 200%
Sodium; To High	0 0%	0 0%	0 0%

28. Secondary Outcome

Title	Part 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria
Description	Urine samples were collected from participants for analysis of following urinalysis parameters; specific gravity, pH, presence of glucose, protein, occult blood, ketones in urine analyzed by dipstick method. The dipstick test gives results in a semi-quantitative manner. 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. The reference range is 1.002-1.030. Urine pH is an acid-base measurement. Normal urine has a slightly acid pH (5.0 - 6.0). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the "To Normal or No Change" category.
Time Frame	Up to 60 days

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	15	14
Glucose; To Low	0 0%	0 0%	0 0%
Glucose; To Normal or No Change	15 93.8%	15 500%	14 200%
Glucose; To High	0 0%	0 0%	0 0%
Glucose; To Abnormal	0 0%	0 0%	0 0%
Ketones; To Low	0 0%	0 0%	0 0%
Ketones; To Normal or No Change	14 87.5%	15 500%	14 200%
Ketones; To High	0 0%	0 0%	0 0%
Ketones To Abnormal	1 6.3%	0 0%	0 0%
Occult blood; To Low	0 0%	0 0%	0 0%
Occult blood ; To Normal or No Change	14 87.5%	13 433.3%	10 142.9%
Occult blood; To High	0 0%	0 0%	0 0%
Occult blood To Abnormal	1 6.3%	2 66.7%	4 57.1%
Protein; To Low	0 0%	0 0%	0 0%
Protein; To Normal or No Change	15 93.8%	15 500%	14 200%
Protein; To High	0 0%	0 0%	0 0%
Protein To Abnormal	0 0%	0 0%	0 0%
Specific gravity; To Low	1 6.3%	0 0%	2 28.6%
Specific gravity; To Normal or No Change	14 87.5%	15 500%	12 171.4%
Specific gravity; To High	0 0%	0 0%	0 0%
Specific gravity To Abnormal	0 0%	0 0%	0 0%
Urine pH; To Low	0 0%	0 0%	0 0%
Urine pH; To Normal or No Change	15 93.8%	15 500%	14 200%
Urine pH; To High	0 0%	0 0%	0 0%
Urine pH; To Abnormal	0 0%	0 0%	0 0%

29. Secondary Outcome

Title	Part 1: Blood Pressure at Indicated Time Points
Description	SBP and DBP of participants were measured in supine position after 10 minutes rest at indicated time points.
Time Frame	Day -2; Day -1; Pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	15	14
DBP; DAY -2	68.667 (6.2981)	69.533 (7.6426)	65.000 (6.1893)
DBP; DAY -1	67.467 (6.2320)	68.467 (8.7657)	65.643 (7.7619)
DBP; DAY 1, PREDOSE	65.956 (4.9419)	66.245 (7.1653)	66.929 (7.4379)
DBP; DAY 1, 1 Hour	63.200 (6.1551)	64.133 (6.1163)	67.357 (5.4998)
DBP; DAY 1, 2 Hours	62.133 (5.6552)	62.533 (4.6425)	66.071 (7.1410)
DBP; DAY 1, 4 Hours	63.733 (6.6490)	64.400 (5.3825)	67.429 (5.5152)
DBP; DAY 1, 6 Hours	64.400 (6.1968)	64.067 (7.4878)	66.071 (5.5117)
DBP; DAY 1, 8 Hours	68.333 (6.6940)	66.933 (5.0351)	68.000 (6.1269)
DBP; DAY 1, 12 Hours	68.867 (5.5532)	67.800 (7.2723)	66.214 (5.1766)
DBP; DAY 1, 24 Hours	68.400 (6.4343)	66.533 (6.2663)	66.929 (7.0870)
DBP; DAY 1, 48 Hours	66.600 (7.4431)	67.333 (5.5377)	64.643 (6.1595)
DBP; DAY 1, 72 Hours	66.600 (8.0250)	67.067 (5.2026)	64.429 (7.1545)
SBP; DAY -2	108.667 (9.9115)	109.733 (9.0116)	105.786 (9.8775)
SBP; DAY -1	110.067 (10.2153)	104.000 (9.7980)	108.429 (11.1128)
SBP; DAY 1, PREDOSE	108.156 (9.2400)	108.289 (11.1021)	106.858 (9.5900)
SBP; DAY 1, 1 Hour	106.000 (10.0428)	108.400 (8.3820)	106.500 (9.3377)
SBP; DAY 1, 2 Hours	104.867 (10.6091)	105.067 (9.6323)	106.214 (11.8593)
SBP; DAY 1, 4 Hours	107.733 (9.1844)	106.000 (8.8237)	106.714 (10.8019)
SBP; DAY 1, 6 Hours	108.333 (8.9894)	106.933 (7.1661)	108.214 (11.8008)
SBP; DAY 1, 8 Hours	112.067 (8.9639)	110.600 (12.3508)	106.000 (12.3973)
SBP; DAY 1, 12 Hours	110.133 (10.2181)	113.000 (11.9762)	107.786 (12.1919)
SBP; DAY 1, 24 Hours	106.200 (9.9441)	107.467 (10.8619)	105.500 (11.1061)
SBP; DAY 1, 48 Hours	106.867 (10.1620)	107.067 (6.3860)	102.000 (12.2725)
SBP; DAY 1, 72 Hours	104.067 (11.7075)	105.933 (10.8197)	107.429 (13.5290)

30. Secondary Outcome

Title	Part 1: Change From Baseline in Blood Pressure
Description	SBP and DBP were measured in supine position after 10 minutes rest for the participant at indicated time points. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Time Frame	Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	15	14
DBP; DAY 1, 1 Hour	-2.756 (4.5583)	-2.112 (5.8242)	0.429 (6.2950)
DBP; DAY 1, 2 Hours	-3.823 (4.8274)	-3.712 (7.5868)	-0.857 (6.0936)
DBP; DAY 1, 4 Hours	-2.223 (5.1037)	-1.845 (6.6186)	0.500 (4.4191)
DBP; DAY 1, 6 Hours	-1.556 (4.0795)	-2.179 (5.8416)	-0.857 (6.7412)
DBP; DAY 1, 8 Hours	2.377 (3.8999)	0.688 (7.8368)	1.071 (4.3963)
DBP; DAY 1, 12 Hours	2.911 (6.7287)	1.555 (7.1028)	-0.714 (6.2782)
DBP; DAY 1, 24 Hours	2.444 (4.7072)	0.288 (6.5408)	0.000 (6.3519)
DBP; DAY 1, 48 Hours	0.644 (7.9350)	1.088 (8.1406)	-2.286 (4.2171)
DBP; DAY 1, 72 Hours	0.644 (6.4814)	0.821 (6.3773)	-2.500 (7.5579)
SBP; DAY 1, 1 Hour	-2.156 (5.2225)	0.111 (8.8653)	-0.358 (7.2826)
SBP; DAY 1, 2 Hours	-3.289 (8.9001)	-3.222 (11.2680)	-0.644 (6.9132)
SBP; DAY 1, 4 Hours	-0.423 (7.3588)	-2.289 (10.0523)	-0.144 (8.8536)
SBP; DAY 1, 6 Hours	0.177 (6.2989)	-1.355 (8.9097)	1.356 (9.9739)
SBP; DAY 1, 8 Hours	3.911 (7.8095)	2.311 (11.0679)	-0.858 (10.0987)
SBP; DAY 1, 12 Hours	1.977 (6.7186)	4.711 (7.4998)	0.928 (9.8279)
SBP; DAY 1, 24 Hours	-1.956 (7.9095)	-0.822 (9.2810)	-1.358 (4.6289)
SBP; DAY 1, 48 Hours	-1.289 (4.9058)	-1.222 (10.7458)	-4.858 (9.5294)
SBP; DAY 1, 72 Hours	-4.089 (7.4727)	-2.355 (9.9198)	0.571 (11.2671)

31. Secondary Outcome

Title	Part 1: Pulse Rate at Indicated Time Points
Description	Pulse rate was measured in supine position after 10 minutes rest for the participant at indicated time points.
Time Frame	Day -2; Day -1; Pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	15	14
DAY -2	64.067 (14.6066)	62.333 (10.8737)	60.214 (9.4558)
DAY -1	62.333 (10.6212)	63.067 (7.6108)	59.071 (10.6516)
DAY 1, PREDOSE	65.023 (10.7156)	64.311 (7.9777)	59.857 (8.3402)
DAY 1, 1 Hour	74.667 (8.5996)	72.333 (9.2711)	58.571 (9.3949)
DAY 1, 2 Hours	72.667 (11.8301)	72.933 (9.5877)	60.214 (10.4010)
DAY 1, 4 Hours	68.133 (7.8728)	69.467 (11.0574)	61.214 (9.5287)
DAY 1, 6 Hours	68.867 (9.9417)	68.133 (11.0961)	66.500 (9.4360)
DAY 1, 8 Hours	66.533 (10.5144)	66.933 (7.2552)	63.571 (10.6027)
DAY 1, 12 Hours	64.867 (9.0069)	65.867 (6.4128)	67.143 (11.4546)
DAY 1, 24 Hours	63.400 (7.1992)	61.267 (7.6295)	64.071 (11.5190)
DAY 1, 48 Hours	64.333 (6.7259)	63.533 (6.4572)	63.286 (10.5278)
DAY 1, 72 Hours	62.267 (6.9639)	62.467 (8.0166)	62.286 (11.0900)

32. Secondary Outcome

Title	Part 1: Change From Baseline in Pulse Rate
Description	Pulse rate was measured in supine position after 10 minutes rest for the participant at indicated time points. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Time Frame	Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	15	14
DAY 1, 1 Hour	9.644 (9.2897)	8.023 (9.3536)	-1.286 (4.4390)
DAY 1, 2 Hours	7.644 (10.5927)	8.623 (8.8718)	0.357 (5.2912)
DAY 1, 4 Hours	3.111 (7.1157)	5.156 (10.5863)	1.357 (4.6853)
DAY 1, 6 Hours	3.844 (8.0953)	3.823 (11.4959)	6.643 (2.4580)
DAY 1, 8 Hours	1.511 (9.0965)	2.623 (9.1496)	3.714 (5.1408)
DAY 1, 12 Hours	-0.156 (8.6466)	1.556 (7.3741)	7.286 (8.0517)
DAY 1, 24 Hours	-1.623 (8.9894)	-3.044 (8.7852)	4.214 (6.3150)
DAY 1, 48 Hours	-0.689 (8.0818)	-0.777 (7.8056)	3.429 (7.7752)
DAY 1, 72 Hours	-2.756 (9.7834)	-1.844 (7.4755)	2.429 (6.6210)

33. Secondary Outcome

Title	Part 1: Number of Participants With Abnormal ECG Findings
Description	Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTcF intervals. CS and NCS abnormal ECG findings have been presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.
Time Frame	Day -2, Day -1; 1, 2, 4, 6, 8, , 12, 24, 48, 72 hours on Day 1

Outcome Measure Data

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

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	15	14
NCS: DAY -2; n=15, 15, 14	10 62.5%	9 300%	9 128.6%
CS: DAY -2; n=15, 15, 14	0 0%	0 0%	0 0%
NCS: DAY -1; n=15, 14, 14	7 43.8%	9 300%	12 171.4%
CS: DAY -1; n=15, 14, 14	0 0%	0 0%	0 0%
NCS: DAY 1, 1 Hour; n=15, 15, 14	6 37.5%	5 166.7%	11 157.1%
CS: DAY 1, 1 Hour; n=15, 15, 14	0 0%	0 0%	0 0%
NCS: DAY 1, 2 Hours; n=15, 15, 13	5 31.3%	5 166.7%	10 142.9%
CS: DAY 1, 2 Hours; n=15, 15, 13	0 0%	0 0%	0 0%
NCS: DAY 1, 4 Hours; n=15, 13, 14	5 31.3%	3 100%	13 185.7%
CS: DAY 1, 4 Hours; n=15, 13, 14	0 0%	0 0%	0 0%
NCS: DAY 1, 6 Hours; n=14, 14, 14	3 18.8%	3 100%	5 71.4%
CS: DAY 1, 6 Hours; n=14, 14, 14	0 0%	0 0%	0 0%
NCS: DAY 1, 8 Hours; n=15, 15, 14	7 43.8%	5 166.7%	8 114.3%
CS: DAY 1, 8 Hours; n=15, 15, 14	0 0%	0 0%	0 0%
NCS: DAY 1, 12 Hours; n=15, 14, 14	7 43.8%	4 133.3%	9 128.6%
CS: DAY 1, 12 Hours; n=15, 14, 14	0 0%	0 0%	0 0%
NCS: DAY 1, 24 Hours; n=14, 15, 14	11 68.8%	10 333.3%	10 142.9%
CS: DAY 1, 24 Hours; n=14, 15, 14	0 0%	0 0%	0 0%
NCS: DAY 1, 48 Hours; n=15, 15, 14	8 50%	9 300%	11 157.1%
CS: DAY 1, 48 Hours; n=15, 15, 14	0 0%	0 0%	0 0%
NCS: DAY 1, 72 Hours; n=15, 15, 14	10 62.5%	8 266.7%	11 157.1%
CS: DAY 1, 72 Hours; n=15, 15, 14	0 0%	0 0%	0 0%

34. Secondary Outcome

Title	Part 1: Change From Baseline in Mean Heart Rate Values as ECG Parameter
Description	Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Time Frame	Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 hours on Day 1

Outcome Measure Data

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

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	15	14
DAY 1, 1 Hour; n=15,15,14	11.623 (3.5038)	7.955 (7.1040)	-0.642 (3.6609)
DAY 1, 2 Hours; n=15,15,13	10.623 (4.8877)	8.489 (6.5565)	-1.230 (4.3393)
DAY 1, 4 Hours; n=15,14,14	4.156 (3.2562)	2.500 (7.3292)	2.144 (4.9148)
DAY 1, 6 Hours; n=14,14,14	6.072 (3.0746)	1.643 (7.5799)	5.786 (2.6441)
DAY 1, 8 Hours; n=15,15,14	2.223 (4.5377)	1.489 (7.0631)	2.929 (4.3034)
DAY 1, 12 Hours; n=15,15,14	4.089 (5.0734)	-0.178 (6.3675)	6.072 (5.5851)
DAY 1, 24 Hours; n=15,15,14	-2.377 (6.3879)	-4.711 (7.0854)	2.786 (4.2971)
DAY 1, 48 Hours; n=15,15,14	1.023 (7.7608)	-2.378 (6.3181)	2.358 (6.3093)
DAY 1, 72 Hours; n=15,15,14	-0.911 (6.1612)	-3.045 (6.1332)	2.286 (4.8518)

35. Secondary Outcome

Title	Part 1: Change From Baseline in PR Interval, QRS, QT Interval, and QTcF Interval as ECG Parameters
Description	Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates measures PR, QRS, QT and QTcF intervals. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.
Time Frame	Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 hours on Day 1

Outcome Measure Data

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

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	15	14
PR interval; DAY 1, 1 Hour; n= 15,15,14	-4.667 (8.7068)	-3.067 (8.0354)	-3.000 (4.1236)
PR interval; DAY 1, 2 Hours; n=15,15,13	-6.001 (7.7330)	-8.000 (11.0362)	-1.846 (6.4305)
PR interval; DAY 1, 4 Hours; n=15,14,14	-7.067 (10.2033)	-5.905 (8.8947)	-2.571 (5.2620)
PR interval; DAY 1, 6 Hours; n=14,14,14	-5.286 (8.1501)	-4.048 (7.9887)	-7.286 (6.3330)
PR interval; DAY 1, 8 Hours; n=15,15,14	-2.267 (9.6666)	0.267 (9.2972)	-7.571 (5.4017)
PR interval; DAY 1, 12 Hours; n=15,15,14	3.599 (7.2967)	3.600 (10.7074)	-5.143 (5.5061)
PR interval; DAY 1, 24 Hours; n=15,15,14	0.133 (6.2540)	0.667 (11.6569)	-4.000 (5.2761)
PR interval; DAY 1, 48 Hours; n=15,15,14	0.533 (9.8492)	0.267 (9.7100)	-2.857 (4.9369)
PR interval; DAY 1, 72 Hours; n=15,15,14	0.266 (6.7270)	-0.800 (8.3925)	0.286 (9.5887)
QRS interval; DAY 1, 1 Hour; n=15,15,14	0.177 (4.0981)	-1.067 (2.1485)	-1.191 (2.1266)
QRS interval; DAY 1, 2 Hours; n=15,15,13	-1.289 (2.7414)	-3.601 (5.5916)	-1.949 (3.6451)
QRS interval; DAY 1, 4 Hours; n=15,14,14	-0.223 (4.7522)	-3.144 (5.5231)	-1.334 (3.5564)
QRS interval; DAY 1, 6 Hours; n=14,14,14	1.190 (4.4691)	-1.096 (3.4838)	-0.048 (2.9515)
QRS interval; DAY 1, 8 Hours; n=15,15,14	-1.023 (5.4315)	-1.201 (3.2956)	-1.476 (3.0398)
QRS interval; DAY 1, 12 Hours; n=15,15,14	0.577 (5.0503)	0.266 (3.0628)	-0.905 (2.3614)
QRS interval; DAY 1, 24 Hours; n=15,15,14	-0.489 (3.9399)	-0.001 (3.2548)	-1.762 (2.7249)
QRS interval; DAY 1, 48 Hours; n=15,15,14	-0.489 (4.0107)	-3.601 (5.2408)	-2.905 (2.8351)
QRS interval; DAY 1, 72 Hours; n=15,15,14	0.311 (3.4718)	-1.067 (4.7049)	-1.905 (2.6381)
QT interval; DAY 1, 1 Hour; n=15,15,14	-27.511 (9.5694)	-23.333 (8.8511)	-0.334 (6.8828)
QT interval; DAY 1, 2 Hours; n=15,15,13	-30.844 (12.7773)	-26.266 (8.5061)	1.435 (9.3833)
QT interval; DAY 1, 4 Hours; n=15,14,14	-17.377 (12.8317)	-15.523 (12.6937)	-2.191 (12.9124)
QT interval; DAY 1, 6 Hours; n=14,14,14	-15.524 (10.6107)	-10.619 (14.9602)	-23.334 (16.4029)
QT interval; DAY 1, 8 Hours; n=15,15,14	-9.511 (12.7754)	-6.266 (16.7718)	-12.762 (13.2960)
QT interval; DAY 1, 12 Hours; n=15,15,14	-16.044 (19.7270)	-9.466 (15.0727)	-24.334 (22.8434)
QT interval; DAY 1, 24 Hours; n=15,15,14	-2.044 (14.0881)	0.801 (12.2568)	-11.476 (12.3125)
QT interval; DAY 1, 48 Hours; n=15,15,14	-3.644 (17.8393)	-0.666 (14.5496)	-7.476 (12.3459)
QT interval; DAY 1, 72 Hours; n=15,15,14	-0.977 (15.5657)	0.134 (13.0685)	-12.762 (15.3517)
QTcF interval; DAY 1, 1 Hour; n=15,15,14	-4.666 (10.4724)	-8.868 (7.0866)	-2.285 (11.8494)
QTcF interval; DAY 1, 2 Hours; n=15,15,13	-10.133 (10.8407)	-11.068 (8.0958)	-2.076 (12.2719)
QTcF interval; DAY 1, 4 Hours; n=15,14,14	-8.466 (10.1552)	-11.335 (10.1802)	1.858 (10.9901)
QTcF interval; DAY 1, 6 Hours; n=14,14,14	-3.714 (9.3976)	-7.573 (12.1949)	-10.499 (12.0696)
QTcF interval; DAY 1, 8 Hours; n=15,15,14	-4.333 (11.3261)	-3.268 (14.6848)	-6.356 (11.4959)
QTcF interval; DAY 1, 12 Hours; n=15,15,14	-7.199 (11.5629)	-9.735 (15.8796)	-11.214 (12.2055)
QTcF interval; DAY 1, 24 Hours; n=15,15,14	-6.933 (10.7150)	-9.601 (9.4605)	-5.856 (9.6316)
QTcF interval; DAY 1, 48 Hours; n=15,15,14	-0.999 (12.4826)	-5.601 (5.4868)	-3.785 (9.7479)
QTcF interval; DAY 1, 72 Hours; n=15,15,14	-2.466 (9.5081)	-6.401 (10.0613)	-7.785 (12.1949)

36. Secondary Outcome

Title	Part 1: Tlag Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Tlag is a time delay between drug administration and first observed concentration. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	15	14
Median (Full Range) [Hours]	1.000	1.000	0.500

37. Secondary Outcome

Title	Part 1: Tmax Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	15	14
Median (Full Range) [Hours]	11.967	5.983	3.508

38. Secondary Outcome

Title	Part 1: T1/2 Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	15	14
Geometric Mean (Geometric Coefficient of Variation) [Hours]	15.606 (14.84)	15.692 (17.28)	17.061 (19.01)

39. Secondary Outcome

Title	Part 1: Tlast Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	15	14
Median (Full Range) [Hours]	119.983	119.983	120.017

40. Secondary Outcome

Title	Part 1: Plasma Drug Concentration at 24 Hours (C24) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	15	14
Geometric Mean (Geometric Coefficient of Variation) [Nanograms per milliliter]	84.536 (41.93)	75.643 (32.57)	26.852 (35.39)

41. Secondary Outcome

Title	Part 1: AUC(0-t) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State
Description	Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time Frame	Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed	Part 1: GSK2838232 200 mg/Ritonavir Tablet Fasted
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.	Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.
Measure Participants	15	15	14
Geometric Mean (Geometric Coefficient of Variation) [Hours* nanograms per milliliter]	4595.35 (40.28)	4371.47 (30.03)	1776.21 (36.60)

42. Secondary Outcome

Title	Part 2: Slope of Pre-dose Concentration of GSK2838232 Administered as Non-boosted Once-daily Doses of a Tablet Formulation to Assess Achievement of Steady State
Description	Blood sample were collected at indicated time points to assess pre-dose concentration of GSK2838232 when administered as non-boosted once-daily doses of a tablet formulation for 11 days in Part 2. Slope and 90 percent confidence interval have been presented.
Time Frame	Pre-dose on Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10 and Day 11 in Part 2

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	7
Pre-dose, Days 3-11	-0.00910
Pre-dose, Days 4-11	-0.0150
Pre-dose, Days 5-11	-0.0379
Pre-dose, Days 6-11	-0.0490
Pre-dose, Days 7-11	-0.0679
Pre-dose, Days 8-11	-0.0672
Pre-dose, Days 9-11	-0.107
Pre-dose, Days 10-11	-0.263

43. Secondary Outcome

Title	Part 2: Accumulation Ratio Calculated From AUC(0-tau) Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation
Description	Blood sample were collected at indicated time points to calculate accumulation ratio from AUC(0-tau) following administration of GSK2838232 as non-boosted once-daily doses of a tablet formulation. Accumulation ratio of GSK2838232 was evaluated by Day 11, AUC (0-tau) divided by Day 1, AUC (0-tau).
Time Frame	Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	7
Mean (Standard Deviation) [Ratio of AUC]	1.3340 (0.18272)

44. Secondary Outcome

Title	Part 2: Accumulation Ratio Calculated From Cmax Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation
Description	Blood sample were collected at indicated time points to calculate accumulation ratio from Cmax following administration of GSK2838232 as non-boosted once-daily doses of a tablet formulation. Accumulation ratio of GSK2838232 was evaluated by Day 11, Cmax divided by Day 1, Cmax.
Time Frame	Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	7
Mean (Standard Deviation) [Ratio of Cmax]	1.2118 (0.28582)

45. Secondary Outcome

Title	Part 2: Accumulation Ratio Calculated From Ctau Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation
Description	Blood sample were collected at indicated time points to calculate accumulation ratio from Ctau following administration of GSK2838232 as non-boosted once-daily doses of a tablet formulation. Accumulation ratio of GSK2838232 was evaluated by Day 11, Ctau divided by Day 1, Ctau.
Time Frame	Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
Measure Participants	7
Mean (Standard Deviation) [Ratio of Ctau]	1.3205 (0.32907)

Adverse Events

	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed		Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed		Part 1: GSK 200 mg/Ritonavir Tablet Fasted		Part 2: Placebo		Part 2: GSK2838232 500 mg Tablet Fed
Time Frame	Serious adverse events (SAEs) and Non-SAEs were collected up to 60 days in Part 1 of the study and up to 25 days in Part 2 of the study.
Adverse Event Reporting Description	SAEs and Non-SAEs were reported for the Safety Population which comprised of all participants who received at least 1 dose of the study treatment (including placebo) with at least 1 post-Baseline safety assessment.

Arm/Group Title	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed		Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed		Part 1: GSK 200 mg/Ritonavir Tablet Fasted		Part 2: Placebo		Part 2: GSK2838232 500 mg Tablet Fed
Arm/Group Description	Participants received a single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.		Participants received a single dose of GSK2838232 200 mg (as 2 x 10 mg) tablet formulation along with ritonavir 100 mg tablet administered under fed conditions in treatment periods 1 and 2.		Participants received a single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation under fasted conditions in treatment period 3 along with ritonavir 100 mg tablet to be taken with water in fasted condition.		Eligible participants received single daily doses of placebo tablet orally along with water in fed condition for 11 days.		Eligible participants received non-ritonavir boosted GSK2838232 500 mg, given as single daily doses in fed condition for 11 days.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)		0/14 (0%)		0/3 (0%)		0/7 (0%)
Serious Adverse Events
	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed		Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed		Part 1: GSK 200 mg/Ritonavir Tablet Fasted		Part 2: Placebo		Part 2: GSK2838232 500 mg Tablet Fed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/15 (0%)		0/14 (0%)		0/3 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Part 1: GSK2838232 200 mg/Ritonavir Capsule Fed		Part 1: GSK2838232 200 mg/Ritonavir Tablet Fed		Part 1: GSK 200 mg/Ritonavir Tablet Fasted		Part 2: Placebo		Part 2: GSK2838232 500 mg Tablet Fed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/15 (20%)		2/15 (13.3%)		1/14 (7.1%)		1/3 (33.3%)		0/7 (0%)
Gastrointestinal disorders
Abdominal discomfort	1/15 (6.7%)	1	0/15 (0%)	0	0/14 (0%)	0	0/3 (0%)	0	0/7 (0%)	0
Abdominal pain	1/15 (6.7%)	1	0/15 (0%)	0	0/14 (0%)	0	0/3 (0%)	0	0/7 (0%)	0
Abdominal pain lower	1/15 (6.7%)	1	0/15 (0%)	0	0/14 (0%)	0	0/3 (0%)	0	0/7 (0%)	0
Constipation	1/15 (6.7%)	1	0/15 (0%)	0	0/14 (0%)	0	0/3 (0%)	0	0/7 (0%)	0
Diarrhoea	1/15 (6.7%)	1	0/15 (0%)	0	0/14 (0%)	0	0/3 (0%)	0	0/7 (0%)	0
Flatulence	1/15 (6.7%)	1	0/15 (0%)	0	0/14 (0%)	0	0/3 (0%)	0	0/7 (0%)	0
Vomiting	1/15 (6.7%)	2	0/15 (0%)	0	0/14 (0%)	0	0/3 (0%)	0	0/7 (0%)	0
General disorders
Chest discomfort	0/15 (0%)	0	1/15 (6.7%)	2	0/14 (0%)	0	0/3 (0%)	0	0/7 (0%)	0
Chills	1/15 (6.7%)	1	0/15 (0%)	0	0/14 (0%)	0	0/3 (0%)	0	0/7 (0%)	0
Infusion site pain	0/15 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/3 (0%)	0	0/7 (0%)	0
Injury, poisoning and procedural complications
Skin abrasion	0/15 (0%)	0	1/15 (6.7%)	1	0/14 (0%)	0	0/3 (0%)	0	0/7 (0%)	0
Musculoskeletal and connective tissue disorders
Pain in extremity	0/15 (0%)	0	0/15 (0%)	0	1/14 (7.1%)	1	0/3 (0%)	0	0/7 (0%)	0
Nervous system disorders
Headache	3/15 (20%)	3	0/15 (0%)	0	0/14 (0%)	0	0/3 (0%)	0	0/7 (0%)	0
Syncope	1/15 (6.7%)	1	0/15 (0%)	0	0/14 (0%)	0	0/3 (0%)	0	0/7 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/15 (0%)	0	0/15 (0%)	0	0/14 (0%)	0	1/3 (33.3%)	1	0/7 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

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

Results Point of Contact

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

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT03234036

Other Study ID Numbers:

205820

First Posted:

Jul 31, 2017

Last Update Posted:

Oct 28, 2020

Last Verified:

Oct 1, 2020

A Two-part Study to Compare a Tablet and Capsule Formulation of GSK2838232 With and Without Food, and to Assess the Safety and Drug Levels of Repeated Once-daily Doses of GSK2838232 Without Ritonavir

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Reproductive potential:

Non-reproductive potential:

Exclusion Criteria:

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Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

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Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

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Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

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Results Point of Contact