GSK2983559 First Time in Human Study

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Terminated

CT.gov ID

NCT03358407

Collaborator

(none)

Enrollment

Location

Arms

13.3

Actual Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is the first administration of GSK2983559, a selective receptor interacting protein 2 (RIP2) kinase inhibitor, to humans. This will be randomized, double-blinded (sponsor open) and two part study (A and B). Part A of the study is single ascending dose crossover design with two separate cohorts (1 and 2). In Part A, 9 single dose levels will be explored. In Cohort 1, 10 healthy subjects will randomized to receive single oral doses of either GSK2983559 or placebo in a ratio of 4:1 in 5 way cross-over design with 5 treatment periods. In Cohort 2, 8 healthy subjects will be randomized to receive single oral doses of either GSK2983559 or placebo in a ratio of 3:1 in 4 way cross-overs design with 4 treatment periods. In Cohort 2 there will be an additional period (period 5-open label) for assessing GSK2983559 under fed conditions. There will be 48 hours wash-out period between each dose escalation period. Part B is repeat ascending dose sequential group design. It will contain 4 Cohorts of and dosing will be done sequential dosing. Subjects in Part B will receive once daily (QD) dose or twice daily dose (will be decided based upon the pharmacokinetic, safety and tolerability observed in Part A). There will 58 subjects involved in this study. Total duration of Part A will be approximately for 11 Weeks and Part B will be approximately for 15 Weeks.

Condition or Disease	Intervention/Treatment	Phase
Inflammatory Bowel Diseases	Drug: GSK2983559 Drug: Placebo	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

31 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Single-centre, Randomized, Double-blind (Sponsor Open), Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK2983559, in Single (in Both Fed and Fasted States) and Repeat Oral Doses in Healthy Participants

Actual Study Start Date :

Jan 11, 2018

Actual Primary Completion Date :

Feb 19, 2019

Actual Study Completion Date :

Feb 19, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: Cohort 1 Cohort 1 will be 5-way crossover with 5 treatment periods. Subjects will be randomized in the ratio 4:1 to receive either single dose of GSK2983559 or placebo.	Drug: GSK2983559 GSK2983559 will be available as oral capsules with dose strength of 2-45 milligram (mg), 100 and 114 mg. Drug: Placebo Placebo oral capsules matching GSK2983559 will be available for subjects.
Experimental: Part A: Cohort 2 fasting Cohort 2 will be 4-way crossover design with one additional period of open-label. Subjects will be randomized in the ratio 3:1 to receive either single dose of GSK2983559 or placebo in fasted conditions	Drug: GSK2983559 GSK2983559 will be available as oral capsules with dose strength of 2-45 milligram (mg), 100 and 114 mg. Drug: Placebo Placebo oral capsules matching GSK2983559 will be available for subjects.
Experimental: Part A: Cohort 2 fed In Cohort 2, treatment period 5 will be open-label period. This open-label period is to determine food effect and subjects will receive GSK2983559 under fed conditions.	Drug: GSK2983559 GSK2983559 will be available as oral capsules with dose strength of 2-45 milligram (mg), 100 and 114 mg.
Experimental: Part B Part B is repeat ascending dose sequential period. There will four cohorts (3-6) of 10 healthy subjects. In each cohort subjects will be randomized to receive GSK2983559 or placebo in ratio 4:1. Subjects will receive GSK2983559 or placebo QD and twice daily dose will be decided based upon the pharmacokinetic, safety and tolerability observed in Part A.	Drug: GSK2983559 GSK2983559 will be available as oral capsules with dose strength of 2-45 milligram (mg), 100 and 114 mg. Drug: Placebo Placebo oral capsules matching GSK2983559 will be available for subjects.

Outcome Measures

Primary Outcome Measures

Part A: Number of Participants With Non Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs) [Up to 7 weeks]
An adverse event was 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 was defined as any untoward medical occurrence that, at any dose may result in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgement.
Part B: Number of Participants With Non-SAEs and SAEs [Up to 11 weeks]
An adverse event was 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 was defined as any untoward medical occurrence that, at any dose may result in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Non-SAEs and SAEs were planned to be collected.
Part A: Number of Participants With Worst Case Hematology Parameters of Potential Clinical Importance (PCI) [Up to 7 weeks]
Hematology parameters included hematocrit, hemoglobin, lymphocytes, platelet counts, total neutrophils and white blood cells (WBCs) count. PCI ranges were: hematocrit (high: >0.54 proportion of red blood cells in blood and low: change from baseline<0.0075); hemoglobin (high: >180 grams per liter [g/L] and low: change from baseline<25 g/L); lymphocytes (low: <0.8 Giga cells/L); platelet count (low: <100 Giga cells/L and high: >550 Giga cells/L); neutrophil count (low: <1.5 Giga cells/L); white blood cell count (low: <3 Giga cells/L and high: >20 Giga cells/L). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose 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. Only those hematology parameters with PCI values have been presented.
Part B: Number of Participants With Worst Case Hematology Parameters of PCI [Up to 11 weeks]
Hematology parameters included hematocrit, hemoglobin, lymphocytes, platelet counts, total neutrophils and WBC count. PCI ranges were: hematocrit (high: >0.54 proportion of red blood cells in blood and low: change from baseline<0.0075); hemoglobin (high: >180 grams per liter [g/L] and low: change from baseline<25 g/L); lymphocytes (low: <0.8 Giga cells/L); platelet count (low: <100 Giga cells/L and high: >550 Giga cells/L); neutrophil count (low: <1.5 Giga cells/L); white blood cell count (low: <3 Giga cells/L and high: >20 Giga cells/L). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose 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. Participants with worst case hematology parameters of PCI were planned to be collected.
Part A: Number of Participants With Worst Case Clinical Chemistry Parameters of PCI [Up to 7 weeks]
Clinical chemistry parameters included alanine amino transferase (ALT), albumin, alkaline phosphatase (ALP), aspartate amino transferase (AST), calcium, creatinine, glucose, potassium, sodium and total bilirubin (T.bil). PCI ranges were: ALT, AST, ALP (high): >=2*Upper limit of Normal(ULN) units per liter(U/L), albumin(low): 30 g/L, calcium: <2(low) or >2.75 millimoles per liter (mmol/L)(high), creatinine (high): increase from Baseline >44.2 micromoles per liter(µmol/L), glucose: <3(low) or >9 mmol/L(high), potassium: <3(low) or >5.5 mmol/L(high), sodium: <130(low) or >150 mmol/L(high) and T.bil(high): >=1.5*ULN (µmol/L). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose 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 B: Number of Participants With Worst Case Clinical Chemistry Parameters of PCI [Up to 11 weeks]
Clinical chemistry parameters included ALT, albumin, alkaline phosphatase, AST, calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were ALT(high): >=2*ULN U/L, albumin(low): 30 g/L, alkaline phosphatase(high): >=2*ULN U/L, AST(high): >=2*ULN U/L, calcium: <2(low) or >2.75 mmol/L (high), creatinine (high): increase from Baseline >44.25 µmol/L, glucose: <3(low) or >9 mmol/L(high), potassium: <3(low) or >5.5 mmol/L(high), sodium: <130(low) or >150 mmol/L(high) and total bilirubin(high): >=1.5*ULN (µmol/L). Participants with worst case clinical chemistry parameters of PCI were planned to be collected.
Part A: Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method [Up to 7 weeks]
Urine samples were collected to assess glucose, ketones, occult blood and protein by dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters glucose, ketones, occult blood and protein were categorized as 'any increase from Baseline', which imply any increase in their concentrations in the urine sample. Baseline was defined as latest predose (Day 1) assessment with a non-missing value.
Part B: Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method [Up to 11 weeks]
Urine analysis included assessment of glucose, ketones, occult blood and protein by dipstick method. The dipstick test gives results in a semi-quantitative manner. Baseline was defined as latest predose (Day 1) assessment with a non-missing value. Participants with worst case any increase in urinalysis results post-Baseline relative to Baseline were planned to be collected.
Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings [1.5, 2, 2.5, 3, 4, 5, 8, 12, 24 and 48 hours post-dose]
12-lead ECGs were obtained using an ECG machine. Only those participants who had any abnormal ECG findings are presented. Abnormal ECG findings were categorized as clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings. Clinically significant 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 B: Number of Participants With Abnormal ECG Findings [Up to 11 weeks]
12-lead ECGs were planned to be obtained using an ECG machine. Abnormal ECG findings were categorized as CS and NCS abnormal ECG findings. 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. Participants with any abnormal ECG findings were planned to be evaluated.
Part A: Number of Participants With Worst Case Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) Values of PCI [Up to 7 weeks]
DBP and SBP were measured in semi-supine position after 5 minutes rest. PCI ranges included DBP: <45 millimeters of mercury (mmHg) (lower) and >100 mmHg (higher) and SBP: <85 mmHg (lower) and >160 mmHg (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose 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 B: Number of Participants With Worst Case DBP and SBP Values of PCI [Up to 11 weeks]
DBP and SBP were measured in semi-supine position after 5 minutes rest. PCI ranges included DBP: <45 mmHg (lower) and >100 mmHg (higher) and SBP: <85 mmHg (lower) and >160 mmHg (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose 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. Participants with worst case DBP and SBP values of PCI were planned to be evaluated.
Part A: Number of Participants With Worst Case Respiration Rate Values of PCI [Up to 7 weeks]
Respiration rate was measured in semi-supine position after 5 minutes rest. PCI ranges included <=8 breaths per minute (lower) and >=20 breaths per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose 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 B: Number of Participants With Worst Case Respiration Rate Values of PCI [Up to 11 weeks]
Respiration rate was measured in semi-supine position after 5 minutes rest. PCI ranges included <=8 breaths per minute (lower) and >=20 breaths per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose 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. Participants with worst case respiratory rate values of PCI were planned to be evaluated.
Part A: Number of Participants With Worst Case Heart Rate Values of PCI [Up to 7 weeks]
Heart rate was measured in semi-supine position after 5 minutes rest. PCI ranges included <40 beats per minute (lower) and >110 beats per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose 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 B: Number of Participants With Worst Case Heart Rate Values of PCI [Up to 11 weeks]
Heart rate was measured in semi-supine position after 5 minutes rest. PCI ranges included <40 beats per minute (lower) and >110 beats per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose 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. Participants with worst case heart rate values of PCI were planned to be evaluated.
Part A: Number of Participants With Worst Case Body Temperature Values of PCI [Up to 7 weeks]
Body temperature was measured in semi-supine position after 5 minutes rest. PCI ranges included <=35.5 degrees Celsius (lower) and >=37.8 degrees Celsius (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose 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 B: Number of Participants With Worst Case Body Temperature Values of PCI [Up to 11 weeks]
Body temperature was measured in semi-supine position after 5 minutes rest. PCI ranges included <=35.5 degrees Celsius (lower) and >=37.8 degrees Celsius (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose 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. Participants with worst case body temperature values of PCI were planned to be evaluated.
Part A: Number of Participants With Abnormal Findings in Physical Examination [Up to 7 weeks]
Physical examinations included assessment of the skin, cardiovascular, respiratory, and gastrointestinal systems. This analysis was not planned and data was not collected and not captured in the database.
Part B: Number of Participants With Abnormal Findings in Physical Examination [Up to 11 weeks]
Physical examinations included assessment of the skin, cardiovascular, respiratory, and gastrointestinal systems. Data was not collected and not captured in the database.
Part A: Change From Baseline in Activated Partial Thromboplastin Time and Prothrombin Time at Indicated Time Points [Baseline (Day 1, Pre-dose), 24 and 48 hours post-dose]
Blood samples were collected to evaluate activated partial thromboplastin time (APTT) and prothrombin time (PT) at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Part B: Change From Baseline in Activated Partial Thromboplastin Time and Prothrombin Time at Indicated Time Points [Baseline and Up to 11 weeks]
Blood samples were planned to be collected to evaluate PTT and PT at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Part A: Change From Baseline in International Normalized Ratio at Indicated Time Points [Baseline (Day 1, Pre-dose), 24 and 48 hours]
Blood samples were collected to evaluate international normalized ratio at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Part B: Change From Baseline in International Normalized Ratio at Indicated Time Points [Baseline and Up to 11 weeks]
Blood samples were planned to be collected to evaluate international normalized ratio at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Secondary Outcome Measures

Part A (Cohort 1): Area Under Plasma Concentration-time Curve (AUC) From Zero Hours to Time of Last Quantifiable Concentration (AUC[0-t]) for GSK2983559 [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Part A (Cohort 2): AUC(0-t) for GSK2983559 [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Part A (Cohort 1): AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part A (Cohort 2): AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part A (Cohort 1): AUC From Time Zero to Infinity (AUC[0-inf]) for GSK2983559 [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure AUC(0-inf) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Part A (Cohort 2): AUC(0-inf) for GSK2983559 [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure AUC(0-inf) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Part A (Cohort 1): AUC(0-inf) for GSK2668176 (Active Moiety of GSK2983559) [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure AUC(0-inf) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part A (Cohort 2): AUC(0-inf) for GSK2668176 (Active Moiety of GSK2983559) [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure AUC(0-inf) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part A (Cohort 1): Maximum Plasma Concentration (Cmax) for GSK2983559 [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Part A (Cohort 2): Cmax for GSK2983559 [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Part A (Cohort 1): Cmax for GSK2668176 (Active Moiety of GSK2983559) [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part A (Cohort 2): Cmax for GSK2668176 (Active Moiety of GSK2983559) [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part A (Cohort 1): Terminal Elimination Half-life (T1/2) for GSK2983559 [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure T1/2 at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Part A (Cohort 2): T1/2 for GSK2983559 [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure T1/2 at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Part A (Cohort 1): T1/2 for GSK2668176 (Active Moiety of GSK2983559) [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure T1/2 at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part A (Cohort 2): T1/2 for GSK2668176 (Active Moiety of GSK2983559) [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure T1/2 at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part A (Cohort 1): Time to Cmax (Tmax) for GSK2983559 [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Part A (Cohort 2): Tmax for GSK2983559 [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Part A (Cohort 1): Tmax for GSK2668176 (Active Moiety of GSK2983559) [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part A (Cohort 2): Tmax for GSK2668176 (Active Moiety of GSK2983559) [Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part B: AUC(0-t) for GSK2983559 Following Single Dose on Day 1 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period]
Blood samples were planned to be collected to measure AUC(0-t) at indicated time-points.
Part B: AUC(0-t) for GSK2983559 on Day 14 [Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were planned to be collected to measure AUC(0-t) at indicated time-points.
Part B: AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period]
Blood samples were planned to be collected to measure AUC(0-t) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part B: AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) on Day 14 [Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were planned to be collected to measure AUC(0-t) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part B: AUC From 0 Hours to the Time of Next Dosing AUC(0-tau) for GSK2983559 Following Single Dose on Day 1 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period]
Blood samples were planned to be collected to measure AUC(0-tau) at indicated time-points.
Part B: AUC(0-tau) for GSK2983559 on Day 14 [Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were planned to be collected to measure AUC(0-tau) at indicated time-points.
Part B: AUC(0-tau) for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period]
Blood samples were planned to be collected to measure AUC(0-tau) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part B: AUC(0-tau) for GSK2668176 (Active Moiety of GSK2983559) on Day 14 [Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were planned to be collected to measure AUC(0-tau) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part B: Cmax for GSK2983559 Following Single Dose on Day 1 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period]
Blood samples were planned to be collected to measure Cmax at indicated time-points.
Part B: Cmax for GSK2983559 on Day 14 [Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were planned to be collected to measure Cmax at indicated time-points.
Part B: Cmax for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period]
Blood samples were planned to be collected to measure Cmax at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part B: Cmax for GSK2668176 (Active Moiety of GSK2983559) on Day 14 [Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were planned to be collected to measure Cmax at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part B: Tmax for GSK2983559 Following Single Dose on Day 1 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period]
Blood samples were planned to be collected to measure Tmax at indicated time-points.
Part B: Tmax for GSK2983559 on Day 14 [Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were planned to be collected to measure Tmax at indicated time-points.
Part B: Tmax for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period]
Blood samples were planned to be collected to measure Tmax at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part B: Tmax for GSK2668176 (Active Moiety of GSK2983559) on Day 14 [Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were planned to be collected to measure Tmax at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part B: T1/2 for GSK2983559 Following Single Dose on Day 1 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period]
Blood samples were planned to be collected to measure T1/2 at indicated time-points.
Part B: T1/2 for GSK2983559 on Day 14 [Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were planned to be collected to measure T1/2 at indicated time-points.
Part B: T1/2 for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period]
Blood samples were planned to be collected to measure T1/2 at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part B: T1/2 for GSK2668176 (Active Moiety of GSK2983559) on Day 14 [Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were planned to be collected to measure T1/2 at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part B: Accumulation Ratio of GSK2983559 [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were planned to be collected to measure accumulation ratio at indicated time-points. Accumulation ratio was to be calculated as ratio of AUC(0-tau) at Day 14 to AUC(0-tau) at Day 1.
Part B: Accumulation Ratio of GSK2668176 (Active Moiety of GSK2983559) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period]
Blood samples were planned to be collected to measure accumulation ratio at indicated time-points. Accumulation ratio was to be calculated as ratio of AUC(0-tau) at Day 14 to AUC(0-tau) at Day 1. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part A (Cohort 2): AUC (0-t) for GSK2983559 in Fasted Condition (Period 4) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4]
Blood samples were planned to be collected to measure AUC(0-t) in fasted condition (Period 4) at indicated time-points.
Part A (Cohort 2): AUC(0-t) for GSK2983559 in Fed Condition (Period 5) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5]
Blood samples were planned to be collected to measure AUC(0-t) in fed condition (Period 5) at indicated time-points.
Part A (Cohort 2): AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4]
Blood samples were planned to be collected to measure AUC(0-t) in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part A (Cohort 2): AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5]
Blood samples were planned to be collected to measure AUC(0-t) in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part A (Cohort 2): AUC(0-inf) for GSK2983559 in Fasted Condition (Period 4) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4]
Blood samples were planned to be collected to measure AUC(0-inf) in fasted condition (Period 4) at indicated time-points.
Part A (Cohort 2): AUC(0-inf) for GSK2983559 in Fed Condition (Period 5) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5]
Blood samples were planned to be collected to measure AUC(0-inf) in fed condition (Period 5) at indicated time-points.
Part A (Cohort 2): AUC(0-inf) for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4]
Blood samples were planned to be collected to measure AUC(0-inf) in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part A (Cohort 2): AUC(0-inf) for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5]
Blood samples were planned to be collected to measure AUC(0-inf) in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part A (Cohort 2): Cmax for GSK2983559 in Fasted Condition (Period 4) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4]
Blood samples were planned to be collected to measure Cmax in fasted condition (Period 4) at indicated time-points.
Part A (Cohort 2): Cmax for GSK2983559 in Fed Condition (Period 5) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5]
Blood samples were planned to be collected to measure Cmax in fed condition (Period 5) at indicated time-points.
Part A (Cohort 2): Cmax for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4]
Blood samples were planned to be collected to measure Cmax in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part A (Cohort 2): Cmax for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5]
Blood samples were planned to be collected to measure Cmax in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part A (Cohort 2): Tmax for GSK2983559 in Fasted Condition (Period 4) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4]
Blood samples were planned to be collected to measure Tmax in fasted condition (Period 4) at indicated time-points.
Part A (Cohort 2): Tmax for GSK2983559 in Fed Condition (Period 5) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5]
Blood samples were planned to be collected to measure Tmax in fed condition (Period 5) at indicated time-points.
Part A (Cohort 2): Tmax for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4]
Blood samples were planned to be collected to measure Tmax in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part A (Cohort 2): Tmax for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5]
Blood samples were planned to be collected to measure Tmax in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part A (Cohort 2): T1/2 for GSK2983559 in Fasted Condition (Period 4) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4]
Blood samples were planned to be collected to measure T1/2 in fasted condition (Period 4) at indicated time-points.
Part A (Cohort 2): T1/2 for GSK2983559 in Fed Condition (Period 5) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5]
Blood samples were planned to be collected to measure T1/2 in fed condition (Period 5) at indicated time-points.
Part A (Cohort 2): T1/2 for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4]
Blood samples were planned to be collected to measure T1/2 in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Part A (Cohort 2): T1/2 for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5) [Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5]
Blood samples were planned to be collected to measure T1/2 in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Male and female subjects between 18 and 65 years of age inclusive, at the time of signing the informed consent.
Volunteers who are overtly healthy as determined by medical evaluation including medical and psychiatric history, physical examination, neurological examination, clinical laboratory tests and cardiac monitoring.
3Body weight >= 50 kg (kilogram) and body mass index (BMI) within the range 19-32 kilogram per meter square (kg/m^2) .
A male subject must agree to use a highly effective contraception during the treatment period and for at least 5 half-lives plus an additional 90 days after the last dose of study treatment and refrain from donating sperm during this period.
A female subject is eligible to participate if she is not pregnant, not breastfeeding, and is not a woman of childbearing potential (WOCBP)
Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Participants must agree to avoid prolonged Ultraviolet (UV) exposure to natural sunlight without required Ultraviolet A (UVA)/ Ultraviolet B (UVB) protection or tanning beds for the duration of the study.

Exclusion Criteria:

History or presence of/significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
History or current evidence of febrile seizures, epilepsy, convulsions, significant head injury, or other significant neurologic conditions.
History of clinically significant psychiatric disorders as judged by the investigator.
Any history of suicidal behavior within the past 6 months or any history of attempted suicide in a subject's lifetime.
ALT >1.5x upper limit of normal (ULN).
Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
History of Gastrointestinal (GI) surgery (with exception of appendectomy)
Average QTc > 450 millisecond (msec)
Intended use of over-the-counter or prescription medication including herbal medications within 7 days prior to dosing
Live or attenuated vaccine(s) within 30 days of randomization, or plans to receive such vaccines during the study or plans to receive a vaccine within 30 days + 5 half-lives of the last dose of study medication.
Regular alcohol consumption within 6 months prior to the study defined as: An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half pint (approximately 240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
Current use or history of regular tobacco- or nicotine-containing products within 6 months prior to screening. Subject must have urinary cotinine levels indicative of non-smoking status at screening visit.
Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
Current enrollment or past participation within the last 30 days before signing of consent in this or any other clinical study involving an investigational study treatment or any other type of medical research.
Subjects with impaired renal function defined as Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) calculation <= 60 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2) estimated by the CKD-EPI equation.
An elevated C-reactive protein (CRP) outside of the normal reference range.
Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment. As potential for and magnitude of immunosuppression with this compound is unknown, subjects with presence of hepatitis B core antibody (HBcAb) should also be excluded. Subjects positive for HBsAg and/or positive for anti-HBc antibody (regardless of anti-HBs antibody status) are excluded.
A positive pre-study drug/alcohol screen.
A positive test for HIV antibody.
A positive diagnostic TB test at screening defined as a positive QuantiFERON-TB Gold test or T-spot test. In cases where the QuantiFERON or T-spot test is indeterminate, the subject may have the test repeated once, but they will not be eligible for the study unless the second test is negative. In cases where the QuantiFERON or T-spot test is positive, but a locally-read follow up chest x-ray, shows no evidence of current or previous pulmonary tuberculosis, the subject may be eligible for the study at the discretion of the Investigator and GSK Medical Monitor.
Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the Investigator or GSK Medical Monitor, contraindicates participation in the study.
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56-day period.
Part A (Food Effect) Cohort: Subject must have no dietary restrictions (e.g., lactose intolerance) or inability to eat a high fat meal.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Cambridge	Cambridgeshire	United Kingdom	CB2 2GG

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT03358407

Other Study ID Numbers:

205021
2017-002664-40

First Posted:

Nov 30, 2017

Last Update Posted:

Nov 27, 2020

Last Verified:

Nov 1, 2020

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

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

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

Keywords provided by GlaxoSmithKline

Inflammatory Bowel disease

Pro-drug

Double-blinded

Crossover

Additional relevant MeSH terms:

Intestinal Diseases

Inflammatory Bowel Diseases

Study Results

Participant Flow

Recruitment Details	This was a 2-part study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of GSK2983559 in healthy participants. The study was terminated early due to non-clinical toxicology findings and reduced safety margins. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.
Pre-assignment Detail	A total of 85 participants were screened, of them, 54 participants were screen failures and 31 participants were enrolled and received study treatment in Part A. The study was terminated during Cohort 2 of Part A, hence no participants were enrolled in period 3, 4 and 5 (Cohort 2) of Part A and in Part B.

Arm/Group Title	Part A-Cohort 1: Placebo/GSK 4mg/GSK 10mg/GSK 30mg/GSK 100mg	Part A-Cohort 1: GSK 2mg/Placebo/GSK 10mg/GSK 30mg/GSK 100mg	Part A-Cohort 1: GSK 2mg/GSK 4mg/Placebo/GSK 30mg/GSK 100mg	Part A-Cohort 1: GSK 2mg/GSK 4mg/GSK 10mg/Placebo/GSK 100mg	Part A-Cohort 1: GSK 2mg/GSK 4mg/GSK 10mg/GSK 30mg/Placebo	Part A-Cohort 2: Placebo/GSK 400mg	Part A-Cohort 2: GSK 200mg/Placebo	Part A-Cohort 2: GSK 200mg/GSK 400mg	Part B: Placebo	Part B: GSK2983559
Arm/Group Description	Participants (Par.) received oral single dose of placebo matching GSK2983559 (GSK) in treatment period 1 followed by 4 milligram (mg) GSK2983559 in treatment period 2 followed by 10 mg GSK2983559 in treatment period 3 followed by 30 mg GSK2983559 in treatment period 4 followed by 100 mg GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up (FU) visit after 14 days of last period.	Participants received oral single dose of 2 mg GSK2983559 in treatment period 1 followed by placebo matching GSK2983559 in treatment period 2 followed by 10 mg GSK2983559 in treatment period 3 followed by 30 mg GSK2983559 in treatment period 4 followed by 100 mg GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period.	Participants received oral single dose of 2 mg GSK2983559 in treatment period 1 followed by 4 mg GSK2983559 in treatment period 2 followed by placebo matching GSK2983559 in treatment period 3 followed by 30 mg GSK2983559 in treatment period 4 followed by 100 mg GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period.	Participants received oral single dose of 2 mg GSK2983559 in treatment period 1 followed by 4 mg GSK2983559 in treatment period 2 followed by 10 mg GSK2983559 in treatment period 3 followed by placebo matching GSK2983559 in treatment period 4 followed by 100 mg GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period.	Participants received oral single dose of 2 mg GSK2983559 in treatment period 1 followed by 4 mg GSK2983559 in treatment period 2 followed by 10 mg GSK2983559 in treatment period 3 followed by 30 mg GSK2983559 in treatment period 4 followed by placebo matching GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period.	Participants were administered oral single dose of placebo matching GSK2983559 in treatment period 1 followed by 400 mg GSK2983559 in treatment period 2. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. The periods 3, 4, and 5 were planned but no participants were enrolled in those periods due to early terminated of study. The study was terminated during period 2 of Part A-Cohort 2.	Participants were administered oral single dose of 200 mg GSK2983559 in treatment period 1 followed by placebo matching GSK2983559 in treatment period 2. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. The periods 3, 4, and 5 were planned but no participants were enrolled in those periods due to early terminated of study. The study was terminated during period 2 of Part A-Cohort 2.	Participants were administered oral single dose of 200 mg GSK2983559 in treatment period 1 followed by 400 mg GSK2983559 in treatment period 2. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. The periods 3, 4, and 5 were planned but no participants were enrolled in those periods due to early terminated of study. The study was terminated during period 2 of Part A-Cohort 2.	Participants were planned to be administered placebo matching GSK2983559 either once daily or twice daily. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Period Title: P1:PartA-Cohort1(4days)+Washout(48hours)
STARTED	2	2	2	2	2	0	0	0	0	0
COMPLETED	2	2	2	2	2	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0
Period Title: P1:PartA-Cohort1(4days)+Washout(48hours)
STARTED	2	2	2	2	2	0	0	0	0	0
COMPLETED	2	2	1	2	2	0	0	0	0	0
NOT COMPLETED	0	0	1	0	0	0	0	0	0	0
Period Title: P1:PartA-Cohort1(4days)+Washout(48hours)
STARTED	2	2	2	2	2	0	0	0	0	0
COMPLETED	2	2	2	2	2	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0
Period Title: P1:PartA-Cohort1(4days)+Washout(48hours)
STARTED	2	2	2	2	2	0	0	0	0	0
COMPLETED	2	2	2	2	1	0	0	0	0	0
NOT COMPLETED	0	0	0	0	1	0	0	0	0	0
Period Title: P1:PartA-Cohort1(4days)+Washout(48hours)
STARTED	2	2	2	2	2	0	0	0	0	0
COMPLETED	2	2	2	2	2	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0
Period Title: P1:PartA-Cohort1(4days)+Washout(48hours)
STARTED	0	0	0	0	0	3	3	6	0	0
COMPLETED	0	0	0	0	0	0	2	3	0	0
NOT COMPLETED	0	0	0	0	0	3	1	3	0	0
Period Title: P1:PartA-Cohort1(4days)+Washout(48hours)
STARTED	0	0	0	0	0	3	3	6	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	3	3	6	0	0
Period Title: P1:PartA-Cohort1(4days)+Washout(48hours)
STARTED	0	0	0	0	0	0	0	0	0	0
COMPLETED	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Part A-Cohort 1: Placebo/GSK 4mg/GSK 10mg/GSK 30mg/GSK 100mg	Part A-Cohort 1: GSK 2mg/Placebo/GSK 10mg/GSK 30mg/GSK 100mg	Part A-Cohort 1: GSK 2mg/GSK 4mg/Placebo/GSK 30mg/GSK 100mg	Part A-Cohort 1: GSK 2mg/GSK 4mg/GSK 10mg/Placebo/GSK 100mg	Part A-Cohort 1: GSK 2mg/GSK 4mg/GSK 10mg/GSK 30mg/Placebo	Part A-Cohort 2: Placebo/GSK 400mg	Part A-Cohort 2: GSK 200mg/ Placebo	Part A-Cohort 2: GSK 200mg/GSK 400mg	Part B: Placebo	Part B: GSK2983559	Total
Arm/Group Description	Participants (Par.) received oral single dose of placebo matching GSK2983559 (GSK) in treatment period 1 followed by 4 milligram (mg) GSK2983559 in treatment period 2 followed by 10 mg GSK2983559 in treatment period 3 followed by 30 mg GSK2983559 in treatment period 4 followed by 100 mg GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up (FU) visit after 14 days of last period.	Participants received oral single dose of 2 mg GSK2983559 in treatment period 1 followed by placebo matching GSK2983559 in treatment period 2 followed by 10 mg GSK2983559 in treatment period 3 followed by 30 mg GSK2983559 in treatment period 4 followed by 100 mg GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period.	Participants received oral single dose of 2 mg GSK2983559 in treatment period 1 followed by 4 mg GSK2983559 in treatment period 2 followed by placebo matching GSK2983559 in treatment period 3 followed by 30 mg GSK2983559 in treatment period 4 followed by 100 mg GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period.	Participants received oral single dose of 2 mg GSK2983559 in treatment period 1 followed by 4 mg GSK2983559 in treatment period 2 followed by 10 mg GSK2983559 in treatment period 3 followed by placebo matching GSK2983559 in treatment period 4 followed by 100 mg GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period.	Participants received oral single dose of 2 mg GSK2983559 in treatment period 1 followed by 4 mg GSK2983559 in treatment period 2 followed by 10 mg GSK2983559 in treatment period 3 followed by 30 mg GSK2983559 in treatment period 4 followed by placebo matching GSK2983559 in treatment period 5. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period.	Participants were administered oral single dose of placebo matching GSK2983559 in treatment period 1 followed by 400 mg GSK2983559 in treatment period 2. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. The periods 3, 4, and 5 were planned but no participants were enrolled in those periods due to early terminated of study. The study was terminated during period 2 of Part A-Cohort 2.	Participants were administered oral single dose of 200 mg GSK2983559 in treatment period 1 followed by placebo matching GSK2983559 in treatment period 2. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. The periods 3, 4, and 5 were planned but no participants were enrolled in those periods due to early terminated of study. The study was terminated during period 2 of Part A-Cohort 2.	Participants were administered oral single dose of 200 mg GSK2983559 in treatment period 1 followed by 400 mg GSK2983559 in treatment period 2. There was a washout period of at least 48-hours between 2 periods. There was a follow up visit after 14 days of last period. The periods 3, 4, and 5 were planned but no participants were enrolled in those periods due to early terminated of study. The study was terminated during period 2 of Part A-Cohort 2.	Participants were planned to be administered placebo matching GSK2983559 either once daily or twice daily. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.	Total of all reporting groups
Overall Participants	2	2	3	2	3	6	4	9	0	0	31
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	38.0 (11.31)	46.0 (14.14)	52.7 (11.85)	45.5 (13.44)	59.3 (4.73)	42.3 (10.50)	33.8 (7.04)	42.8 (11.89)	44.2 (11.73)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 0%
Male	2 100%	2 100%	3 100%	2 100%	3 100%	6 100%	4 100%	9 100%	0 NaN	0 NaN	31 100%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 25%	0 0%	0 NaN	0 NaN	1 3.2%
Asian - Central/South Asian Heritage	0 0%	0 0%	0 0%	1 50%	0 0%	1 16.7%	1 25%	0 0%	0 NaN	0 NaN	3 9.7%
White - White/Caucasian/European Heritage	2 100%	2 100%	3 100%	1 50%	3 100%	5 83.3%	2 50%	9 100%	0 NaN	0 NaN	27 87.1%

Outcome Measures

1. Primary Outcome

Title	Part A: Number of Participants With Non Serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
Description	An adverse event was 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 was defined as any untoward medical occurrence that, at any dose may result in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgement.
Time Frame	Up to 7 weeks

Outcome Measure Data

Analysis Population Description
Safety Population comprised of all randomized participants who received at least one dose of study treatment. Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Arm/Group Title	Part A: Placebo	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of placebo matching GSK2983559 as per randomization schedule.	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	16	8	8	8	8	8	9	9
Non-SAEs	6 300%	2 100%	2 66.7%	1 50%	1 33.3%	2 33.3%	4 100%	4 44.4%
SAEs	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Part B: Number of Participants With Non-SAEs and SAEs
Description	An adverse event was 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 was defined as any untoward medical occurrence that, at any dose may result in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Non-SAEs and SAEs were planned to be collected.
Time Frame	Up to 11 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: Placebo	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered placebo matching GSK2983559 either once daily or twice daily. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0	0

3. Primary Outcome

Title	Part A: Number of Participants With Worst Case Hematology Parameters of Potential Clinical Importance (PCI)
Description	Hematology parameters included hematocrit, hemoglobin, lymphocytes, platelet counts, total neutrophils and white blood cells (WBCs) count. PCI ranges were: hematocrit (high: >0.54 proportion of red blood cells in blood and low: change from baseline<0.0075); hemoglobin (high: >180 grams per liter [g/L] and low: change from baseline<25 g/L); lymphocytes (low: <0.8 Giga cells/L); platelet count (low: <100 Giga cells/L and high: >550 Giga cells/L); neutrophil count (low: <1.5 Giga cells/L); white blood cell count (low: <3 Giga cells/L and high: >20 Giga cells/L). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose 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. Only those hematology parameters with PCI values have been presented.
Time Frame	Up to 7 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Arm/Group Title	Part A: Placebo	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of placebo matching GSK2983559 as per randomization schedule.	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	16	8	8	8	8	8	9	9
Hematocrit, To low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Hematocrit, To within range or no change	16 800%	8 400%	8 266.7%	8 400%	8 266.7%	8 133.3%	9 225%	9 100%
Hematocrit, To high	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Hemoglobin, To low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Hemoglobin, To within range or no change	16 800%	8 400%	8 266.7%	8 400%	8 266.7%	8 133.3%	9 225%	9 100%
Hemoglobin, To high	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Lymphocytes, To low	1 50%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Lymphocytes, To within range or no change	15 750%	8 400%	8 266.7%	8 400%	8 266.7%	8 133.3%	9 225%	9 100%
Lymphocytes, To high	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Platelet count, To low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Platelet count, To within range or no change	16 800%	8 400%	8 266.7%	8 400%	8 266.7%	8 133.3%	9 225%	9 100%
Platelet count, To high	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Total Neutrophils, To low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 25%	0 0%
Total Neutrophils, To within range or no change	16 800%	8 400%	8 266.7%	8 400%	8 266.7%	8 133.3%	8 200%	9 100%
Total Neutrophils, To high	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
WBC count, To low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
WBC count, To within range or no change	16 800%	8 400%	8 266.7%	8 400%	8 266.7%	8 133.3%	9 225%	9 100%
WBC count, To high	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

4. Primary Outcome

Title	Part B: Number of Participants With Worst Case Hematology Parameters of PCI
Description	Hematology parameters included hematocrit, hemoglobin, lymphocytes, platelet counts, total neutrophils and WBC count. PCI ranges were: hematocrit (high: >0.54 proportion of red blood cells in blood and low: change from baseline<0.0075); hemoglobin (high: >180 grams per liter [g/L] and low: change from baseline<25 g/L); lymphocytes (low: <0.8 Giga cells/L); platelet count (low: <100 Giga cells/L and high: >550 Giga cells/L); neutrophil count (low: <1.5 Giga cells/L); white blood cell count (low: <3 Giga cells/L and high: >20 Giga cells/L). Participants were counted in the worst-case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose 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. Participants with worst case hematology parameters of PCI were planned to be collected.
Time Frame	Up to 11 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: Placebo	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered placebo matching GSK2983559 either once daily or twice daily. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0	0

5. Primary Outcome

Title	Part A: Number of Participants With Worst Case Clinical Chemistry Parameters of PCI
Description	Clinical chemistry parameters included alanine amino transferase (ALT), albumin, alkaline phosphatase (ALP), aspartate amino transferase (AST), calcium, creatinine, glucose, potassium, sodium and total bilirubin (T.bil). PCI ranges were: ALT, AST, ALP (high): >=2Upper limit of Normal(ULN) units per liter(U/L), albumin(low): 30 g/L, calcium: <2(low) or >2.75 millimoles per liter (mmol/L)(high), creatinine (high): increase from Baseline >44.2 micromoles per liter(µmol/L), glucose: <3(low) or >9 mmol/L(high), potassium: <3(low) or >5.5 mmol/L(high), sodium: <130(low) or >150 mmol/L(high) and T.bil(high): >=1.5ULN (µmol/L). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose 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 7 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. Data is presented treatment-wise. Only those clinical chemistry parameters with PCI values have been presented. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Arm/Group Title	Part A: Placebo	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of placebo matching GSK2983559 as per randomization schedule.	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	16	8	8	8	8	8	9	9
ALT, To low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
ALT, To within range or no change	16 800%	8 400%	8 266.7%	8 400%	8 266.7%	8 133.3%	9 225%	9 100%
ALT, To high	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Albumin, To low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Albumin, To within range or no change	16 800%	8 400%	8 266.7%	8 400%	8 266.7%	8 133.3%	9 225%	9 100%
Albumin, To high	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
ALP, To low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
ALP, To within range or no change	16 800%	8 400%	8 266.7%	8 400%	8 266.7%	8 133.3%	9 225%	9 100%
ALP, To high	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
AST, To low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
AST, To within range or no change	15 750%	8 400%	8 266.7%	8 400%	8 266.7%	8 133.3%	9 225%	9 100%
AST, To high	1 50%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Calcium, To low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Calcium, To within range or no change	16 800%	8 400%	8 266.7%	8 400%	8 266.7%	8 133.3%	9 225%	9 100%
Calcium, To high	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Creatinine, To low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Creatinine, To within range or no change	16 800%	8 400%	8 266.7%	8 400%	8 266.7%	8 133.3%	9 225%	9 100%
Creatinine, To high	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Glucose, To low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Glucose, To within range or no change	16 800%	8 400%	8 266.7%	8 400%	8 266.7%	8 133.3%	9 225%	9 100%
Glucose, To high	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Potassium, To low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Potassium, To within range or no change	16 800%	8 400%	8 266.7%	8 400%	8 266.7%	8 133.3%	9 225%	9 100%
Potassium, To high	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sodium, To low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sodium, To within range or no change	16 800%	8 400%	8 266.7%	8 400%	8 266.7%	8 133.3%	9 225%	9 100%
Sodium, To high	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
T.bil, To low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
T.bil, To within range or no change	16 800%	8 400%	8 266.7%	8 400%	8 266.7%	8 133.3%	9 225%	9 100%
T.bil, To high	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

6. Primary Outcome

Title	Part B: Number of Participants With Worst Case Clinical Chemistry Parameters of PCI
Description	Clinical chemistry parameters included ALT, albumin, alkaline phosphatase, AST, calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were ALT(high): >=2ULN U/L, albumin(low): 30 g/L, alkaline phosphatase(high): >=2ULN U/L, AST(high): >=2ULN U/L, calcium: <2(low) or >2.75 mmol/L (high), creatinine (high): increase from Baseline >44.25 µmol/L, glucose: <3(low) or >9 mmol/L(high), potassium: <3(low) or >5.5 mmol/L(high), sodium: <130(low) or >150 mmol/L(high) and total bilirubin(high): >=1.5ULN (µmol/L). Participants with worst case clinical chemistry parameters of PCI were planned to be collected.
Time Frame	Up to 11 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: Placebo	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered placebo matching GSK2983559 either once daily or twice daily. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0	0

7. Primary Outcome

Title	Part A: Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Description	Urine samples were collected to assess glucose, ketones, occult blood and protein by dipstick method. The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters glucose, ketones, occult blood and protein were categorized as 'any increase from Baseline', which imply any increase in their concentrations in the urine sample. Baseline was defined as latest predose (Day 1) assessment with a non-missing value.
Time Frame	Up to 7 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Arm/Group Title	Part A: Placebo	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of placebo matching GSK2983559 as per randomization schedule.	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	16	8	8	8	8	8	9	9
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

8. Primary Outcome

Title	Part B: Number of Participants With Worst Case Any Increase in Urinalysis Results Post-Baseline Relative to Baseline by Dipstick Method
Description	Urine analysis included assessment of glucose, ketones, occult blood and protein by dipstick method. The dipstick test gives results in a semi-quantitative manner. Baseline was defined as latest predose (Day 1) assessment with a non-missing value. Participants with worst case any increase in urinalysis results post-Baseline relative to Baseline were planned to be collected.
Time Frame	Up to 11 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: Placebo	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered placebo matching GSK2983559 either once daily or twice daily. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0	0

9. Primary Outcome

Title	Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Description	12-lead ECGs were obtained using an ECG machine. Only those participants who had any abnormal ECG findings are presented. Abnormal ECG findings were categorized as clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings. Clinically significant 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	1.5, 2, 2.5, 3, 4, 5, 8, 12, 24 and 48 hours post-dose

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles). Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Arm/Group Title	Part A: Placebo	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of placebo matching GSK2983559 as per randomization schedule.	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	16	8	8	8	8	8	9	9
Abnormal NCS, 1.5 hours, n=16,8,8,8,8,8,9,9	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 11.1%
Abnormal CS, 1.5 hours, n=16,8,8,8,8,8,9,9	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Abnormal NCS, 2 hours, n=16,8,8,8,8,8,9,9	1 50%	0 0%	0 0%	0 0%	0 0%	1 16.7%	0 0%	1 11.1%
Abnormal CS, 2 hours, n=16,8,8,8,8,8,9,9	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Abnormal NCS, 2.5 hours, n=16,8,8,8,8,8,9,9	0 0%	0 0%	0 0%	1 50%	0 0%	0 0%	0 0%	1 11.1%
Abnormal CS, 2.5 hours, n=16,8,8,8,8,8,9,9	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Abnormal NCS, 3 hours, n=6,0,0,0,0,0,9,9	0 0%	1 50%	0 0%
Abnormal CS, 3 hours, n=6,0,0,0,0,0,9,9	0 0%	0 0%	0 0%
Abnormal NCS, 4 hours, n=16,8,8,8,8,8,9,9	0 0%	0 0%	1 33.3%	1 50%	0 0%	0 0%	0 0%	0 0%
Abnormal CS, 4 hours, n=16,8,8,8,8,8,9,9	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Abnormal NCS, 5 hours, n=6,0,0,0,0,0,9,9	0 0%	0 0%	2 66.7%
Abnormal CS, 5 hours, n=6,0,0,0,0,0,9,9	0 0%	0 0%	0 0%
Abnormal NCS, 8 hours, n=16,8,8,8,8,8,9,9	0 0%	0 0%	1 33.3%	1 50%	0 0%	1 16.7%	0 0%	1 11.1%
Abnormal CS, 8 hours, n=16,8,8,8,8,8,9,9	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Abnormal NCS, 12 hours, n=16,8,8,8,8,8,9,9	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Abnormal CS, 12 hours, n=16,8,8,8,8,8,9,9	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Abnormal NCS, 24 hours, n=16,8,8,8,8,8,9,9	0 0%	0 0%	0 0%	1 50%	1 33.3%	1 16.7%	0 0%	1 11.1%
Abnormal CS, 24 hours, n=16,8,8,8,8,8,9,9	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Abnormal NCS, 48 hours, n=16,8,8,8,8,8,9,9	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Abnormal CS, 48 hours, n=16,8,8,8,8,8,9,9	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

10. Primary Outcome

Title	Part B: Number of Participants With Abnormal ECG Findings
Description	12-lead ECGs were planned to be obtained using an ECG machine. Abnormal ECG findings were categorized as CS and NCS abnormal ECG findings. 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. Participants with any abnormal ECG findings were planned to be evaluated.
Time Frame	Up to 11 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: Placebo	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered placebo matching GSK2983559 either once daily or twice daily. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0	0

11. Primary Outcome

Title	Part A: Number of Participants With Worst Case Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) Values of PCI
Description	DBP and SBP were measured in semi-supine position after 5 minutes rest. PCI ranges included DBP: <45 millimeters of mercury (mmHg) (lower) and >100 mmHg (higher) and SBP: <85 mmHg (lower) and >160 mmHg (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose 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 7 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Arm/Group Title	Part A: Placebo	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of placebo matching GSK2983559 as per randomization schedule.	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	16	8	8	8	8	8	9	9
DBP, To low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
DBP, To within range or no change	16 800%	8 400%	8 266.7%	8 400%	8 266.7%	8 133.3%	9 225%	9 100%
DBP, To high	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
SBP, To low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
SBP, To within range or no change	16 800%	8 400%	8 266.7%	8 400%	8 266.7%	8 133.3%	9 225%	9 100%
SBP, To high	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

12. Primary Outcome

Title	Part B: Number of Participants With Worst Case DBP and SBP Values of PCI
Description	DBP and SBP were measured in semi-supine position after 5 minutes rest. PCI ranges included DBP: <45 mmHg (lower) and >100 mmHg (higher) and SBP: <85 mmHg (lower) and >160 mmHg (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose 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. Participants with worst case DBP and SBP values of PCI were planned to be evaluated.
Time Frame	Up to 11 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: Placebo	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered placebo matching GSK2983559 either once daily or twice daily. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0	0

13. Primary Outcome

Title	Part A: Number of Participants With Worst Case Respiration Rate Values of PCI
Description	Respiration rate was measured in semi-supine position after 5 minutes rest. PCI ranges included <=8 breaths per minute (lower) and >=20 breaths per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose 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 7 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Arm/Group Title	Part A: Placebo	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of placebo matching GSK2983559 as per randomization schedule.	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	16	8	8	8	8	8	9	9
To low	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
To within range or no change	12 600%	7 350%	6 200%	8 400%	7 233.3%	7 116.7%	7 175%	8 88.9%
To high	4 200%	1 50%	2 66.7%	0 0%	1 33.3%	1 16.7%	2 50%	1 11.1%

14. Primary Outcome

Title	Part B: Number of Participants With Worst Case Respiration Rate Values of PCI
Description	Respiration rate was measured in semi-supine position after 5 minutes rest. PCI ranges included <=8 breaths per minute (lower) and >=20 breaths per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose 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. Participants with worst case respiratory rate values of PCI were planned to be evaluated.
Time Frame	Up to 11 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: Placebo	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered placebo matching GSK2983559 either once daily or twice daily. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0	0

15. Primary Outcome

Title	Part A: Number of Participants With Worst Case Heart Rate Values of PCI
Description	Heart rate was measured in semi-supine position after 5 minutes rest. PCI ranges included <40 beats per minute (lower) and >110 beats per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose 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 7 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Arm/Group Title	Part A: Placebo	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of placebo matching GSK2983559 as per randomization schedule.	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	16	8	8	8	8	8	9	9
To low	0 0%	0 0%	0 0%	0 0%	0 0%	1 16.7%	1 25%	0 0%
To within range or no change	16 800%	8 400%	8 266.7%	8 400%	8 266.7%	7 116.7%	8 200%	9 100%
To high	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

16. Primary Outcome

Title	Part B: Number of Participants With Worst Case Heart Rate Values of PCI
Description	Heart rate was measured in semi-supine position after 5 minutes rest. PCI ranges included <40 beats per minute (lower) and >110 beats per minute (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose 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. Participants with worst case heart rate values of PCI were planned to be evaluated.
Time Frame	Up to 11 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: Placebo	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered placebo matching GSK2983559 either once daily or twice daily. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0	0

17. Primary Outcome

Title	Part A: Number of Participants With Worst Case Body Temperature Values of PCI
Description	Body temperature was measured in semi-supine position after 5 minutes rest. PCI ranges included <=35.5 degrees Celsius (lower) and >=37.8 degrees Celsius (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose 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 7 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Arm/Group Title	Part A: Placebo	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of placebo matching GSK2983559 as per randomization schedule.	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	16	8	8	8	8	8	9	9
To low	0 0%	0 0%	1 33.3%	0 0%	0 0%	2 33.3%	1 25%	2 22.2%
To within range or no change	15 750%	8 400%	7 233.3%	8 400%	8 266.7%	6 100%	8 200%	7 77.8%
To high	1 50%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

18. Primary Outcome

Title	Part B: Number of Participants With Worst Case Body Temperature Values of PCI
Description	Body temperature was measured in semi-supine position after 5 minutes rest. PCI ranges included <=35.5 degrees Celsius (lower) and >=37.8 degrees Celsius (higher). Participants were counted in the worst case category that their value changes to (low, or within range or no change, or high), unless there is no change in their category. Participants whose 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. Participants with worst case body temperature values of PCI were planned to be evaluated.
Time Frame	Up to 11 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: Placebo	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered placebo matching GSK2983559 either once daily or twice daily. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0	0

19. Primary Outcome

Title	Part A: Number of Participants With Abnormal Findings in Physical Examination
Description	Physical examinations included assessment of the skin, cardiovascular, respiratory, and gastrointestinal systems. This analysis was not planned and data was not collected and not captured in the database.
Time Frame	Up to 7 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. This analysis was not planned and data was not collected and not captured in the database. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Arm/Group Title	Part A: Placebo	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of placebo matching GSK2983559 as per randomization schedule.	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0	0	0	0	0	0	0

20. Primary Outcome

Title	Part B: Number of Participants With Abnormal Findings in Physical Examination
Description	Physical examinations included assessment of the skin, cardiovascular, respiratory, and gastrointestinal systems. Data was not collected and not captured in the database.
Time Frame	Up to 11 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: Placebo	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered placebo matching GSK2983559 either once daily or twice daily. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0	0

21. Primary Outcome

Title	Part A: Change From Baseline in Activated Partial Thromboplastin Time and Prothrombin Time at Indicated Time Points
Description	Blood samples were collected to evaluate activated partial thromboplastin time (APTT) and prothrombin time (PT) at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1, Pre-dose), 24 and 48 hours post-dose

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). Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Arm/Group Title	Part A: Placebo	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of placebo matching GSK2983559 as per randomization schedule.	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	16	8	8	8	8	8	9	9
APTT, 24 hours, n=16,8,8,7,8,8,9,9	0.4 (3.35)	0.8 (1.83)	2.9 (2.85)	-0.7 (1.80)	1.0 (1.77)	1.0 (2.56)	-1.3 (6.10)	-1.2 (2.11)
APTT, 48 hours, n=16,8,8,8,8,8,8,9	0.5 (2.99)	-0.3 (2.66)	0.5 (3.07)	0.8 (2.38)	0.0 (1.69)	2.3 (2.71)	-3.0 (6.37)	-2.4 (2.96)
PT, 24 hours, n=16,8,8,7,8,8,9,9	0.1 (0.62)	0.3 (0.46)	-0.3 (0.46)	0.1 (0.69)	-0.1 (0.35)	0.1 (0.35)	-0.2 (1.48)	0.0 (0.87)
PT, 48 hours, n=16,8,8,8,8,8,8,9	-0.1 (0.34)	0.0 (0.53)	-0.3 (0.46)	0.1 (0.64)	-0.1 (0.35)	0.1 (0.35)	-0.4 (1.51)	0.1 (0.93)

22. Primary Outcome

Title	Part B: Change From Baseline in Activated Partial Thromboplastin Time and Prothrombin Time at Indicated Time Points
Description	Blood samples were planned to be collected to evaluate PTT and PT at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time Frame	Baseline and Up to 11 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: Placebo	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered placebo matching GSK2983559 either once daily or twice daily. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0	0

23. Primary Outcome

Title	Part A: Change From Baseline in International Normalized Ratio at Indicated Time Points
Description	Blood samples were collected to evaluate international normalized ratio at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time Frame	Baseline (Day 1, Pre-dose), 24 and 48 hours

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). Data is presented treatment-wise. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Arm/Group Title	Part A: Placebo	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of placebo matching GSK2983559 as per randomization schedule.	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	16	8	8	8	8	8	9	9
24 hours, n=16,8,8,7,8,8,9,9	0.001 (0.0496)	0.010 (0.0278)	-0.005 (0.0404)	-0.019 (0.0430)	-0.002 (0.0282)	0.017 (0.0354)	-0.028 (0.1204)	-0.019 (0.0752)
48 hours, n=16,8,8,8,8,8,8,9	-0.018 (0.0248)	0.013 (0.0345)	-0.021 (0.0356)	-0.009 (0.0405)	-0.024 (0.0233)	0.020 (0.0293)	-0.035 (0.1165)	-0.020 (0.0738)

24. Primary Outcome

Title	Part B: Change From Baseline in International Normalized Ratio at Indicated Time Points
Description	Blood samples were planned to be collected to evaluate international normalized ratio at indicated time points. Baseline was defined as latest pre-dose (Day 1) assessment with a non-missing value. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time Frame	Baseline and Up to 11 weeks

Outcome Measure Data

Analysis Population Description
Safety Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: Placebo	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered placebo matching GSK2983559 either once daily or twice daily. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0	0

25. Secondary Outcome

Title	Part A (Cohort 1): Area Under Plasma Concentration-time Curve (AUC) From Zero Hours to Time of Last Quantifiable Concentration (AUC[0-t]) for GSK2983559
Description	Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population comprised of all participants in the safety population who had at least 1 non-missing pharmacokinetic assessment. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg
Arm/Group Description	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.
Measure Participants	8	8	8	6	8
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanogram per milliliter]	NA (NA)	NA (NA)	NA (NA)	1.4088 (38.9)	7.2488 (63.5)

26. Secondary Outcome

Title	Part A (Cohort 2): AUC(0-t) for GSK2983559
Description	Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	9	9
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanogram per milliliter]	8.1765 (61.7)	5.9980 (67.3)

27. Secondary Outcome

Title	Part A (Cohort 1): AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559)
Description	Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg
Arm/Group Description	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.
Measure Participants	8	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanogram per milliliter]	96.7389 (19.3)	250.6231 (36.3)	390.3911 (17.5)	889.6956 (17.2)	2760.8122 (41.3)

28. Secondary Outcome

Title	Part A (Cohort 2): AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559)
Description	Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	9	9
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanogram per milliliter]	2608.4326 (59.7)	2857.1378 (39.9)

29. Secondary Outcome

Title	Part A (Cohort 1): AUC From Time Zero to Infinity (AUC[0-inf]) for GSK2983559
Description	Blood samples were collected to measure AUC(0-inf) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg
Arm/Group Description	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.
Measure Participants	8	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanogram per milliliter]	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)

30. Secondary Outcome

Title	Part A (Cohort 2): AUC(0-inf) for GSK2983559
Description	Blood samples were collected to measure AUC(0-inf) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	9	9
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanogram per milliliter]	NA (NA)	NA (NA)

31. Secondary Outcome

Title	Part A (Cohort 1): AUC(0-inf) for GSK2668176 (Active Moiety of GSK2983559)
Description	Blood samples were collected to measure AUC(0-inf) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg
Arm/Group Description	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.
Measure Participants	8	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanogram per milliliter]	104.28 (19.4)	257.28 (36.0)	405.39 (16.0)	911.53 (17.1)	2860.23 (43.0)

32. Secondary Outcome

Title	Part A (Cohort 2): AUC(0-inf) for GSK2668176 (Active Moiety of GSK2983559)
Description	Blood samples were collected to measure AUC(0-inf) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	9	9
Geometric Mean (Geometric Coefficient of Variation) [Hours*nanogram per milliliter]	2717.46 (57.5)	2950.11 (38.5)

33. Secondary Outcome

Title	Part A (Cohort 1): Maximum Plasma Concentration (Cmax) for GSK2983559
Description	Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

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

Arm/Group Title	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg
Arm/Group Description	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.
Measure Participants	8	8	2	8	8
Geometric Mean (Geometric Coefficient of Variation) [Nanograms per milliliter]	NA (NA)	NA (NA)	0.2291 (12.4)	0.4034 (37.3)	1.1937 (40.2)

34. Secondary Outcome

Title	Part A (Cohort 2): Cmax for GSK2983559
Description	Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	9	9
Geometric Mean (Geometric Coefficient of Variation) [Nanograms per milliliter]	1.3931 (69.3)	1.1244 (70.0)

35. Secondary Outcome

Title	Part A (Cohort 1): Cmax for GSK2668176 (Active Moiety of GSK2983559)
Description	Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg
Arm/Group Description	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.
Measure Participants	8	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Nanograms per milliliter]	10.4980 (34.5)	25.9587 (38.6)	38.4341 (35.5)	93.8714 (19.5)	305.9839 (33.0)

36. Secondary Outcome

Title	Part A (Cohort 2): Cmax for GSK2668176 (Active Moiety of GSK2983559)
Description	Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	9	9
Geometric Mean (Geometric Coefficient of Variation) [Nanograms per milliliter]	314.2321 (113.3)	351.0316 (68.9)

37. Secondary Outcome

Title	Part A (Cohort 1): Terminal Elimination Half-life (T1/2) for GSK2983559
Description	Blood samples were collected to measure T1/2 at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg
Arm/Group Description	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.
Measure Participants	8	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Hours]	NA (NA)	NA (NA)	NA (NA)	NA (NA)	NA (NA)

38. Secondary Outcome

Title	Part A (Cohort 2): T1/2 for GSK2983559
Description	Blood samples were collected to measure T1/2 at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	9	9
Geometric Mean (Geometric Coefficient of Variation) [Hours]	NA (NA)	NA (NA)

39. Secondary Outcome

Title	Part A (Cohort 1): T1/2 for GSK2668176 (Active Moiety of GSK2983559)
Description	Blood samples were collected to measure T1/2 at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg
Arm/Group Description	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.
Measure Participants	8	8	8	8	8
Geometric Mean (Geometric Coefficient of Variation) [Hours]	7.044 (33.2)	8.304 (26.9)	9.649 (26.9)	8.717 (23.0)	9.799 (24.7)

40. Secondary Outcome

Title	Part A (Cohort 2): T1/2 for GSK2668176 (Active Moiety of GSK2983559)
Description	Blood samples were collected to measure T1/2 at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	9	9
Geometric Mean (Geometric Coefficient of Variation) [Hours]	10.480 (20.4)	9.526 (25.6)

41. Secondary Outcome

Title	Part A (Cohort 1): Time to Cmax (Tmax) for GSK2983559
Description	Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

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

Arm/Group Title	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg
Arm/Group Description	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.
Measure Participants	8	8	2	8	8
Median (Full Range) [Hours]	NA	NA	4.500	4.005	4.000

42. Secondary Outcome

Title	Part A (Cohort 2): Tmax for GSK2983559
Description	Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	9	9
Median (Full Range) [Hours]	3.506	4.000

43. Secondary Outcome

Title	Part A (Cohort 1): Tmax for GSK2668176 (Active Moiety of GSK2983559)
Description	Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part A-Cohort 1: GSK2983559 2 mg	Part A-Cohort 1: GSK2983559 4 mg	Part A-Cohort 1: GSK2983559 10 mg	Part A-Cohort 1: GSK2983559 30 mg	Part A-Cohort 1: GSK2983559 100 mg
Arm/Group Description	All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.	All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.
Measure Participants	8	8	8	8	8
Median (Full Range) [Hours]	3.000	2.758	4.006	4.037	3.000

44. Secondary Outcome

Title	Part A (Cohort 2): Tmax for GSK2668176 (Active Moiety of GSK2983559)
Description	Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Pre-dose and at 15 and 30 minutes; 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	9	9
Median (Full Range) [Hours]	3.083	3.500

45. Secondary Outcome

Title	Part B: AUC(0-t) for GSK2983559 Following Single Dose on Day 1
Description	Blood samples were planned to be collected to measure AUC(0-t) at indicated time-points.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

46. Secondary Outcome

Title	Part B: AUC(0-t) for GSK2983559 on Day 14
Description	Blood samples were planned to be collected to measure AUC(0-t) at indicated time-points.
Time Frame	Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

47. Secondary Outcome

Title	Part B: AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Description	Blood samples were planned to be collected to measure AUC(0-t) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

48. Secondary Outcome

Title	Part B: AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Description	Blood samples were planned to be collected to measure AUC(0-t) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

49. Secondary Outcome

Title	Part B: AUC From 0 Hours to the Time of Next Dosing AUC(0-tau) for GSK2983559 Following Single Dose on Day 1
Description	Blood samples were planned to be collected to measure AUC(0-tau) at indicated time-points.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

50. Secondary Outcome

Title	Part B: AUC(0-tau) for GSK2983559 on Day 14
Description	Blood samples were planned to be collected to measure AUC(0-tau) at indicated time-points.
Time Frame	Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

51. Secondary Outcome

Title	Part B: AUC(0-tau) for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Description	Blood samples were planned to be collected to measure AUC(0-tau) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

52. Secondary Outcome

Title	Part B: AUC(0-tau) for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Description	Blood samples were planned to be collected to measure AUC(0-tau) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

53. Secondary Outcome

Title	Part B: Cmax for GSK2983559 Following Single Dose on Day 1
Description	Blood samples were planned to be collected to measure Cmax at indicated time-points.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

54. Secondary Outcome

Title	Part B: Cmax for GSK2983559 on Day 14
Description	Blood samples were planned to be collected to measure Cmax at indicated time-points.
Time Frame	Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

55. Secondary Outcome

Title	Part B: Cmax for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Description	Blood samples were planned to be collected to measure Cmax at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

56. Secondary Outcome

Title	Part B: Cmax for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Description	Blood samples were planned to be collected to measure Cmax at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

57. Secondary Outcome

Title	Part B: Tmax for GSK2983559 Following Single Dose on Day 1
Description	Blood samples were planned to be collected to measure Tmax at indicated time-points.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

58. Secondary Outcome

Title	Part B: Tmax for GSK2983559 on Day 14
Description	Blood samples were planned to be collected to measure Tmax at indicated time-points.
Time Frame	Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

59. Secondary Outcome

Title	Part B: Tmax for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Description	Blood samples were planned to be collected to measure Tmax at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

60. Secondary Outcome

Title	Part B: Tmax for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Description	Blood samples were planned to be collected to measure Tmax at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

61. Secondary Outcome

Title	Part B: T1/2 for GSK2983559 Following Single Dose on Day 1
Description	Blood samples were planned to be collected to measure T1/2 at indicated time-points.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

62. Secondary Outcome

Title	Part B: T1/2 for GSK2983559 on Day 14
Description	Blood samples were planned to be collected to measure T1/2 at indicated time-points.
Time Frame	Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

63. Secondary Outcome

Title	Part B: T1/2 for GSK2668176 (Active Moiety of GSK2983559) Following Single Dose on Day 1
Description	Blood samples were planned to be collected to measure T1/2 at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

64. Secondary Outcome

Title	Part B: T1/2 for GSK2668176 (Active Moiety of GSK2983559) on Day 14
Description	Blood samples were planned to be collected to measure T1/2 at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

65. Secondary Outcome

Title	Part B: Accumulation Ratio of GSK2983559
Description	Blood samples were planned to be collected to measure accumulation ratio at indicated time-points. Accumulation ratio was to be calculated as ratio of AUC(0-tau) at Day 14 to AUC(0-tau) at Day 1.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

66. Secondary Outcome

Title	Part B: Accumulation Ratio of GSK2668176 (Active Moiety of GSK2983559)
Description	Blood samples were planned to be collected to measure accumulation ratio at indicated time-points. Accumulation ratio was to be calculated as ratio of AUC(0-tau) at Day 14 to AUC(0-tau) at Day 1. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 48 hours post-dose in each period

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in Part B due to study termination during Part A.

Arm/Group Title	Part B: GSK2983559
Arm/Group Description	Participants were planned to be administered GSK2983559 in repeat ascending dose sequential period either once daily or twice daily based upon the pharmacokinetic, safety and tolerability observed in Part A. Though, no participants were enrolled in Part B since the study was terminated during Part A due to non-clinical toxicology findings and reduced safety margins.
Measure Participants	0

67. Secondary Outcome

Title	Part A (Cohort 2): AUC (0-t) for GSK2983559 in Fasted Condition (Period 4)
Description	Blood samples were planned to be collected to measure AUC(0-t) in fasted condition (Period 4) at indicated time-points.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

68. Secondary Outcome

Title	Part A (Cohort 2): AUC(0-t) for GSK2983559 in Fed Condition (Period 5)
Description	Blood samples were planned to be collected to measure AUC(0-t) in fed condition (Period 5) at indicated time-points.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

69. Secondary Outcome

Title	Part A (Cohort 2): AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4)
Description	Blood samples were planned to be collected to measure AUC(0-t) in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

70. Secondary Outcome

Title	Part A (Cohort 2): AUC(0-t) for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5)
Description	Blood samples were planned to be collected to measure AUC(0-t) in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

71. Secondary Outcome

Title	Part A (Cohort 2): AUC(0-inf) for GSK2983559 in Fasted Condition (Period 4)
Description	Blood samples were planned to be collected to measure AUC(0-inf) in fasted condition (Period 4) at indicated time-points.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

72. Secondary Outcome

Title	Part A (Cohort 2): AUC(0-inf) for GSK2983559 in Fed Condition (Period 5)
Description	Blood samples were planned to be collected to measure AUC(0-inf) in fed condition (Period 5) at indicated time-points.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

73. Secondary Outcome

Title	Part A (Cohort 2): AUC(0-inf) for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4)
Description	Blood samples were planned to be collected to measure AUC(0-inf) in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

74. Secondary Outcome

Title	Part A (Cohort 2): AUC(0-inf) for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5)
Description	Blood samples were planned to be collected to measure AUC(0-inf) in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

75. Secondary Outcome

Title	Part A (Cohort 2): Cmax for GSK2983559 in Fasted Condition (Period 4)
Description	Blood samples were planned to be collected to measure Cmax in fasted condition (Period 4) at indicated time-points.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

76. Secondary Outcome

Title	Part A (Cohort 2): Cmax for GSK2983559 in Fed Condition (Period 5)
Description	Blood samples were planned to be collected to measure Cmax in fed condition (Period 5) at indicated time-points.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

77. Secondary Outcome

Title	Part A (Cohort 2): Cmax for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4)
Description	Blood samples were planned to be collected to measure Cmax in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

78. Secondary Outcome

Title	Part A (Cohort 2): Cmax for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5)
Description	Blood samples were planned to be collected to measure Cmax in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

79. Secondary Outcome

Title	Part A (Cohort 2): Tmax for GSK2983559 in Fasted Condition (Period 4)
Description	Blood samples were planned to be collected to measure Tmax in fasted condition (Period 4) at indicated time-points.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

80. Secondary Outcome

Title	Part A (Cohort 2): Tmax for GSK2983559 in Fed Condition (Period 5)
Description	Blood samples were planned to be collected to measure Tmax in fed condition (Period 5) at indicated time-points.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

81. Secondary Outcome

Title	Part A (Cohort 2): Tmax for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4)
Description	Blood samples were planned to be collected to measure Tmax in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

82. Secondary Outcome

Title	Part A (Cohort 2): Tmax for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5)
Description	Blood samples were planned to be collected to measure Tmax in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

83. Secondary Outcome

Title	Part A (Cohort 2): T1/2 for GSK2983559 in Fasted Condition (Period 4)
Description	Blood samples were planned to be collected to measure T1/2 in fasted condition (Period 4) at indicated time-points.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

84. Secondary Outcome

Title	Part A (Cohort 2): T1/2 for GSK2983559 in Fed Condition (Period 5)
Description	Blood samples were planned to be collected to measure T1/2 in fed condition (Period 5) at indicated time-points.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

85. Secondary Outcome

Title	Part A (Cohort 2): T1/2 for GSK2668176 (Active Moiety of GSK2983559) in Fasted Condition (Period 4)
Description	Blood samples were planned to be collected to measure T1/2 in fasted condition (Period 4) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 4

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 4 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

86. Secondary Outcome

Title	Part A (Cohort 2): T1/2 for GSK2668176 (Active Moiety of GSK2983559) in Fed Condition (Period 5)
Description	Blood samples were planned to be collected to measure T1/2 in fed condition (Period 5) at indicated time-points. GSK2668176 is the active moiety of pro-drug GSK2983559.
Time Frame	Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 hours post-dose in Period 5

Outcome Measure Data

Analysis Population Description
Pharmacokinetic Population. Data was not collected as no participants were enrolled in period 5 of cohort 2 of Part A as the study was terminated during period 2 of cohort 2 of Part A.

Arm/Group Title	Part A-Cohort 2: GSK2983559 200 mg	Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of 200 mg GSK2983559 in Period 1.	All participants received single oral dose of 400 mg GSK2983559 in Period 2.
Measure Participants	0	0

Adverse Events

	Part A: Placebo		Part A-Cohort 1: GSK2983559 2 mg		Part A-Cohort 1: GSK2983559 4 mg		Part A-Cohort 1: GSK2983559 10 mg		Part A-Cohort 1: GSK2983559 30 mg		Part A-Cohort 1: GSK2983559 100 mg		Part A-Cohort 2: GSK2983559 200 mg		Part A-Cohort 2: GSK2983559 400 mg
Time Frame	Non-SAEs and SAEs were reported from start of study treatment (Day 1) up to Week 7 for Part A
Adverse Event Reporting Description	Non-SAEs and SAEs were reported for Safety Population. Adverse events were presented treatment-wise. Data is presented for Part A only as data was not collected in Part B due to the study was terminated during Part A, and Part B was not initiated. Placebo arms across similar dosing strategies were combined as pre-specified in reporting and analysis plan.

Arm/Group Title	Part A: Placebo		Part A-Cohort 1: GSK2983559 2 mg		Part A-Cohort 1: GSK2983559 4 mg		Part A-Cohort 1: GSK2983559 10 mg		Part A-Cohort 1: GSK2983559 30 mg		Part A-Cohort 1: GSK2983559 100 mg		Part A-Cohort 2: GSK2983559 200 mg		Part A-Cohort 2: GSK2983559 400 mg
Arm/Group Description	All participants received single oral dose of placebo matching GSK2983559 as per randomization schedule.		All participants received single oral dose of 2 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.		All participants received single oral dose of 4 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.		All participants received single oral dose of 10 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.		All participants received single oral dose of 30 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.		All participants received single oral dose of 100 mg GSK2983559 either in Period 1 or Period 2 or Period 3 or Period 4 or Period 5 as per randomization schedule.		All participants received single oral dose of 200 mg GSK2983559 in Period 1.		All participants received single oral dose of 400 mg GSK2983559 in Period 2.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/9 (0%)		0/9 (0%)
Serious Adverse Events
	Part A: Placebo		Part A-Cohort 1: GSK2983559 2 mg		Part A-Cohort 1: GSK2983559 4 mg		Part A-Cohort 1: GSK2983559 10 mg		Part A-Cohort 1: GSK2983559 30 mg		Part A-Cohort 1: GSK2983559 100 mg		Part A-Cohort 2: GSK2983559 200 mg		Part A-Cohort 2: GSK2983559 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/9 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Part A: Placebo		Part A-Cohort 1: GSK2983559 2 mg		Part A-Cohort 1: GSK2983559 4 mg		Part A-Cohort 1: GSK2983559 10 mg		Part A-Cohort 1: GSK2983559 30 mg		Part A-Cohort 1: GSK2983559 100 mg		Part A-Cohort 2: GSK2983559 200 mg		Part A-Cohort 2: GSK2983559 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/16 (37.5%)		2/8 (25%)		2/8 (25%)		1/8 (12.5%)		1/8 (12.5%)		2/8 (25%)		4/9 (44.4%)		4/9 (44.4%)
Cardiac disorders
Tachycardia	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Gastrointestinal disorders
Diarrhoea	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
General disorders
Influenza like illness	2/16 (12.5%)	2	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Catheter site erythema	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Vessel puncture site pain	0/16 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Infections and infestations
Nasopharyngitis	0/16 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/9 (0%)	0	1/9 (11.1%)	1
Tooth abscess	0/16 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Upper respiratory tract infection	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Injury, poisoning and procedural complications
Arthropod bite	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Investigations
Blood creatine phosphokinase increased	1/16 (6.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Body temperature increased	1/16 (6.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Liver function test increased	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1
Musculoskeletal and connective tissue disorders
Joint stiffness	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/9 (0%)	0	0/9 (0%)	0
Musculoskeletal discomfort	1/16 (6.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Nervous system disorders
Headache	1/16 (6.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Lethargy	1/16 (6.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	2/16 (12.5%)	2	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Cough	1/16 (6.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Productive cough	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Respiratory tract irritation	0/16 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/9 (0%)	0	0/9 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/9 (0%)	0	2/9 (22.2%)	2
Capillaritis	0/16 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0
Dermatitis contact	0/16 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/9 (0%)	0	0/9 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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

Results Point of Contact

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

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT03358407

Other Study ID Numbers:

205021
2017-002664-40

First Posted:

Nov 30, 2017

Last Update Posted:

Nov 27, 2020

Last Verified:

Nov 1, 2020