A Safety and Pharmacokinetic (PK) Study of GSK2982772 in Healthy Subjects

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT03305419

Collaborator

(none)

Enrollment

Location

Arms

12.1

Actual Duration (Months)

5.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is designed to evaluate the safety, tolerability and PK of GSK2982772, in repeat oral doses in healthy subjects. This study is being conducted to support administration of higher dose levels of GSK2982772 than initially studied in the First Time in Human (FTiH) study. This study will also assess the impact of food during the repeat doses of GSK2982772. This will be a two part study; Part A and Part B. Part A (cohort 1) - single ascending dose, randomized, placebo-controlled, 3-way crossover. Part B (cohorts 2, 3, 4 and 5) - repeat dose, randomized, placebo-controlled, sequential-group. Subjects will be randomized in 3:1 ratio to receive GSK2982772 or placebo in crossover manner on Day 1 of each of the three periods in Part A. Subjects will be randomized in 3:1 ratio to receive GSK2982772 or placebo in sequential groups for 14 days in cohort 2 of Part B and in 9:5 ratio to receive GSK2982772 or placebo in sequential groups for 14 days in cohorts 3, 4 and 5 of Part B. Approximately 66 subjects will be included in this study. The study duration, including screening and follow-up, will not be expected to exceed 13 weeks for Part A and 8 weeks for Part B.

Condition or Disease	Intervention/Treatment	Phase
Autoimmune Diseases	Drug: GSK2982772 capsule Drug: Placebo capsule	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

62 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

This study will consist of two parts; Part A and Part B. Part A will be a 3-way crossover design and Part B will be a sequential-group design.This study will consist of two parts; Part A and Part B. Part A will be a 3-way crossover design and Part B will be a sequential-group design.

Masking:

Double (Participant, Investigator)

Masking Description:

This will be a double-blind study. Subjects and investigator will be masked.

Primary Purpose:

Treatment

Official Title:

A Single-centre, Randomized, Double-blind (Sponsor-unblinded), Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK2982772 in Repeat Oral Doses in Healthy Subjects

Actual Study Start Date :

Oct 11, 2017

Actual Primary Completion Date :

Oct 15, 2018

Actual Study Completion Date :

Oct 15, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Subjects receiving treatment sequence ABC in cohort 1: Part A Eligible subjects will be randomized to receive treatment sequence ABC in Part A; A= GSK2982772 120 mg TID, B= GSK2982772 240 mg TID, and C= GSK2982772 360 mg BID. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens.	Drug: GSK2982772 capsule GSK2982772 will be available as size 00, white, opaque capsule containing white to almost white Solid (120 mg maximum fill per capsule). It will be administered orally with water to receive total dose of 120 mg, 240 mg or 360 mg per randomization. Drug: Placebo capsule Placebo will be available as size 00, white, opaque capsule containing white to almost white Solid. It will be administered orally with water.
Experimental: Subjects receiving treatment sequence ABP in cohort 1: Part A Eligible subjects will be randomized to receive treatment sequence ABP in Part A; A= GSK2982772 120 mg TID, B= GSK2982772 240 mg TID, and P= Placebo. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens.	Drug: GSK2982772 capsule GSK2982772 will be available as size 00, white, opaque capsule containing white to almost white Solid (120 mg maximum fill per capsule). It will be administered orally with water to receive total dose of 120 mg, 240 mg or 360 mg per randomization. Drug: Placebo capsule Placebo will be available as size 00, white, opaque capsule containing white to almost white Solid. It will be administered orally with water.
Experimental: Subjects receiving treatment sequence APC in cohort 1: Part A Eligible subjects will be randomized to receive treatment sequence APC in Part A; A= GSK2982772 120 mg TID, P= Placebo and C= GSK2982772 360 mg BID. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens.	Drug: GSK2982772 capsule GSK2982772 will be available as size 00, white, opaque capsule containing white to almost white Solid (120 mg maximum fill per capsule). It will be administered orally with water to receive total dose of 120 mg, 240 mg or 360 mg per randomization. Drug: Placebo capsule Placebo will be available as size 00, white, opaque capsule containing white to almost white Solid. It will be administered orally with water.
Experimental: Subjects receiving treatment sequence PBC in cohort 1: Part A Eligible subjects will be randomized to receive treatment sequence PBC in Part A; P= Placebo, B= GSK2982772 240 mg TID and C= GSK2982772 360 mg BID. Subjects will receive oral capsule of GSK2982772 or placebo on Day 1 in each of the 3 treatment periods followed by a wash-out period of at least 7 days between dosing regimens.	Drug: GSK2982772 capsule GSK2982772 will be available as size 00, white, opaque capsule containing white to almost white Solid (120 mg maximum fill per capsule). It will be administered orally with water to receive total dose of 120 mg, 240 mg or 360 mg per randomization. Drug: Placebo capsule Placebo will be available as size 00, white, opaque capsule containing white to almost white Solid. It will be administered orally with water.
Experimental: Subjects receiving GSK2982772 120 mg TID in cohort 2 : Part B Eligible subjects will receive GSK2982772 oral capsule with a dose of 120 mg TID for 14 days in Part B.	Drug: GSK2982772 capsule GSK2982772 will be available as size 00, white, opaque capsule containing white to almost white Solid (120 mg maximum fill per capsule). It will be administered orally with water to receive total dose of 120 mg, 240 mg or 360 mg per randomization.
Experimental: Subjects receiving GSK2982772 120 mg TID in cohort 3 : Part B Eligible subjects will receive GSK2982772 oral capsule with a dose of 120 mg TID for 14 days in Part B.	Drug: GSK2982772 capsule GSK2982772 will be available as size 00, white, opaque capsule containing white to almost white Solid (120 mg maximum fill per capsule). It will be administered orally with water to receive total dose of 120 mg, 240 mg or 360 mg per randomization.
Experimental: Subjects receiving GSK2982772 240 mg TID in cohort 4: Part B Eligible subjects will receive GSK2982772 oral capsule with a dose of 240 mg TID for 14 days in Part B.	Drug: GSK2982772 capsule GSK2982772 will be available as size 00, white, opaque capsule containing white to almost white Solid (120 mg maximum fill per capsule). It will be administered orally with water to receive total dose of 120 mg, 240 mg or 360 mg per randomization.
Experimental: Subjects receiving GSK2982772 360 mg BID in cohort 5: Part B Eligible subjects will receive GSK2982772 oral capsule with a dose of 360 mg BID for 14 days in Part B.	Drug: GSK2982772 capsule GSK2982772 will be available as size 00, white, opaque capsule containing white to almost white Solid (120 mg maximum fill per capsule). It will be administered orally with water to receive total dose of 120 mg, 240 mg or 360 mg per randomization.
Placebo Comparator: Subjects receiving placebo in cohort 2 : Part B Subjects will receive placebo oral capsule for 14 days in Part B.	Drug: Placebo capsule Placebo will be available as size 00, white, opaque capsule containing white to almost white Solid. It will be administered orally with water.
Placebo Comparator: Subjects receiving placebo in cohort 3 : Part B Subjects will receive placebo oral capsule for 14 days in Part B.	Drug: Placebo capsule Placebo will be available as size 00, white, opaque capsule containing white to almost white Solid. It will be administered orally with water.
Placebo Comparator: Subjects receiving placebo in cohort 4 : Part B Subjects will receive placebo oral capsule for 14 days in Part B.	Drug: Placebo capsule Placebo will be available as size 00, white, opaque capsule containing white to almost white Solid. It will be administered orally with water.
Placebo Comparator: Subjects receiving placebo in cohort 5: Part B Subjects will receive placebo oral capsule for 14 days in Part B.	Drug: Placebo capsule Placebo will be available as size 00, white, opaque capsule containing white to almost white Solid. It will be administered orally with water.

Outcome Measures

Primary Outcome Measures

Number of Subjects With Adverse Events (AEs) and Serious AEs (SAEs): Part A [Up to Day 14]
An AE is any untoward medical occurrence in a clinical study subjects, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.
Number of Participants With AEs and SAEs: Part B [Up to Day 28]
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE.
Number of Participants With Worst Case Clinical Chemistry Parameters by Potential Clinical Importance Criteria: Part A [Up to Week 9]
Blood samples were collected from participants for the analysis of following clinical chemistry parameters: alanine amino transferase (ALT), albumin, alkaline phosphatase, aspartate amino transferase (AST), calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were >=2 times Upper Limit of Normal (ULN) units per liter (U/L) for ALT, <30 grams per liter (g/L) for albumin, >=2 times ULN U/L for alkaline phosphatase, >=2 times ULN U/L for AST, <2 or >2.75 millimoles per liter (mmol/L) for calcium, >44.2 micromoles per liter (µmol/L) for creatinine, <3 or >9 mmol/L for glucose, <3 or >5.5 mmol/L for potassium, <130 or >150 mmol/L for sodium and >=1.5 times ULN for total bilirubin. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Number of Participants With Worst Case Clinical Chemistry Parameters by Potential Clinical Importance Criteria: Part B [Up to Week 4]
Blood samples were collected from participants for the analysis of following clinical chemistry parameters: ALT, albumin, alkaline phosphatase, AST, calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were >=2 times ULN U/L for ALT, <30 g/L for albumin, >=2 times ULN U/L for alkaline phosphatase, >=2 times ULN U/L for AST, <2 or >2.75 mmol/L for calcium, >44.2 µmol/L for creatinine, <3 or >9 mmol/L for glucose, <3 or >5.5 mmol/L for potassium, <130 or >150 mmol/L for sodium and >=1.5 times ULN for total bilirubin. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Number of Participants With Worst Case Hematology Parameters by Potential Clinical Importance Criteria: Part A [Up to Week 9]
Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, lymphocytes, platelet count, total neutrophils and white blood cell (WBC) counts. PCI ranges were >0.54 or < 0.075 proportion of red blood cells (RBC) in blood for hematocrit, <25 or >180 g/L for hemoglobin, 0.8 x10^9 cells/L for lymphocytes, <1.5 x10^9 cells/L for neutrophils, <100 or >550 x10^9 cells/L for platelets and <3 or 20> x 10^9 cells per liter WBC. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Number of Participants With Worst Case Hematology Parameters by Potential Clinical Importance Criteria: Part B [Up to Week 4]
Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, lymphocytes, platelet count, total neutrophils and WBC counts. PCI ranges were >0.54 or < 0.075 proportion of RBC in blood for hematocrit, <25 or >180 g/L for hemoglobin, 0.8 x10^9 cells/L for lymphocytes, <1.5 x10^9 cells/L for neutrophils, <100 or >550 x10^9 cells/L for platelets and <3 or 20> x 10^9 cells per liter WBC. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Number of Participants With Worst Case Urinalysis Results: Part A [Up to Week 9]
Urine samples were collected from participants for analysis of following parameters: cellular casts, granular casts, hyaline casts, RBC and WBC and were counted as cells per high-power field (cells/HPF). The number of participants with cells in urine has been presented.
Number of Participants With Worst Case Urinalysis Results: Part B [Up to Week 4]
Urine samples were collected from participants for analysis of following parameters: cellular casts, granular casts, hyaline casts, RBC and WBC and were counted as cells per high-power field (cells/HPF). The number of participants with cells in urine has been presented.
Number of Participants With Abnormal Vital Signs: Part A [Up to Week 9]
Vital signs were measured in a supine position after 5 minutes rest. The PCI criteria for vital signs included: systolic blood pressure <85 and >160 millimeters of mercury [mmHg]), diastolic blood pressure <45 mmHg and >100 mmHg, heart rate <40 and >100 beats per minute, body temperature <=35.5 and >=37.8 degrees Celsius and respiration rate <=8 and >=20 breaths per minute. Data of participants with potential clinical importance has been reported.
Number of Participants With Abnormal Vital Signs: Part B [Up to Week 4]
Vital signs were measured in a supine position after 5 minutes rest. The PCI criteria for vital signs included: systolic blood pressure <85 and >160 mmHg, diastolic blood pressure <45 mmHg and >100 mmHg, heart rate <40 and >100 beats per minute, body temperature <=35.5 and >=37.8 degrees Celsius and respiration rate <=8 and >=20 breaths per minute. Data of participants with potential clinical importance has been reported.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings: Part A [Up to Day 4]
12-lead ECG's were obtained in the supine position after 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant and not clinically significant abnormal ECG findings have been presented. 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.
Number of Participants With Abnormal ECG Findings: Part B [Up to Week 4]
12-lead ECG's were obtained in the supine position after 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant and not clinically significant abnormal ECG findings have been presented. 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.

Secondary Outcome Measures

Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours (AUC[0-24]) Following TID Dosing of GSK2982772: Part A [Pre-dose, 20, 40minutes, 1 hour, 1hr 30min, 2, 3, 5, 7hour, 7hr 20min,and 7hr 40 min, 8hr, 8hr 30min, 9hr, 10hr, 12hr, 14hr, 14hr 20min, 14hr 40 min, 15hr, 15hr 30min, 16hr, 17hr, 19hr, 22hr, 24hours post dose on Day1]
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
AUC(0-24) Following BID Dosing of GSK2982772: Part A [Pre-dose, 20min, 40min, 1hr, 1hr 30min, 2hr, 3hr, 4hr, 6hr, 8hr, 10hr, 12hr, 12hr 20min, 12hr 40min, 13hr, 13hr 30min, 14hr, 15hr, 16hr, 19hr, 22hr, 24hr post dose on Day 1.]
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
AUC[0-24] Following TID Dosing of GSK2982772: Part B [Pre-dose, 20, 40minutes, 1 hour, 1hr 30min, 2, 3, 5, 7hour, 7hr 20min,and 7hr 40 min, 8hr, 8hr 30min, 9hr, 10hr, 12hr, 14hr, 14hr 20min, 14hr 40 min, 15hr, 15hr 30min, 16hr, 17hr, 19hr, 22hr, 24hours post dose on Day14]
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
AUC (0-7) Following TID Dosing of GSK2982772 : Part A [Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Day 1]
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
AUC (7-14) Following TID Dosing of GSK2982772 : Part A [7 hours, 7 hours 20 and 40 minutes, 8 hours, 8 hours 30 minutes, 9, 10, 12, 14 hours on Day 1]
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
AUC (14-24) Following TID Dosing of GSK2982772 : Part A [14 hours, 14 hours 20 and 40 minutes, 15 hours ,15 hours 30 minutes, 16, 19, 22 and 24 hours on Day 1]
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
AUC (0-12) Following BID Dosing of GSK2982772 in Part A [Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 4, 6, 8, 10 hours,12 hours on Day 1]
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
AUC (12-24) Following BID Dosing of GSK2982772 in Part A [12 hours, 12 hours 20 and 40 minutes, 13 and 13 hours 30 minutes, 14, 15, 16, 19, 22 and 24 hours on Day 1]
Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
AUC(0-7) Following TID Dosing of GSK2982772 in Part B [Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 1 and 14]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
AUC (7-14) Following TID Dosing of GSK2982772 in Part B [7 and 7 hours 20 and 40 minutes, 8 and 8 hours 30 minutes, 9, 10, 12, 14 hours on Day 14]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
AUC (14-24) Following TID Dosing of GSK2982772 in Part B [14 hours, 14 hours 20 minutes, 14 hours 40 minutes, 15 hours, 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours on Day 14]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Maximum Observed Plasma Drug Concentration Cmax (0-7) Following TID Dosing of GSK2982772 in Part A [Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, and 7 hours post dose on Day 1]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Cmax (7-14) Following TID Dosing of GSK2982772 in Part A [7 hours, 7 hours 20 and 40 minutes, 8 and 8 hours 30 minutes, 9, 10, 12, 14 hours post dose on Day 1]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Cmax (14-24) Following TID Dosing of GSK2982772 in Part A [14 hours, 14 hours 20 and 40 minutes, 15 and 15 hours 30 minutes, 16, 19, 22 and 24 hours post dose on Day 1]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Cmax (0-12) Following BID Dosing of GSK2982772 in Part A [Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 4, 6, 8, 10 hours and 12 hours post dose on Day 1]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Cmax (12-24) Following BID Dosing of GSK2982772 in Part A [12 hours, 12 hours 20 and 40 minutes, 13 and 13 hours 30 minutes, 14, 15, 16, 19, 22 and 24 hours post dose on Day 1]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Cmax (0-7) Following TID Dosing of GSK2982772 in Part B [Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours post dose on Days 1 and 14]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Cmax (7-14) Following TID Dosing of GSK2982772 in Part B [7hours, 7 hours 20 and 40 minutes, 8 hours, 8 hours 30 minutes, 9, 10, 12, 14 hours on Day 14]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Cmax (14-24) Following TID Dosing of GSK2982772 in Part B [14 hours, 14 hours 20 and 40 minutes, 15 hours, 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours post dose on Day 14]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time to Cmax (Tmax) (0-7) Following TID Dosing of GSK2982772 in Part A [Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, and 7 hours post dose on Day 1]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Tmax (7-14) Following TID Dosing of GSK2982772 in Part A [7hours, 7 hours 20 and 40 minutes, 8 hours, 8 hours 30 minutes, 9, 10, 12, 14 hours post dose on Day 1]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Tmax (14-24) Following TID Dosing of GSK2982772 in Part A [14 hours, 14 hours 20 and 40 minutes, 15 hours, 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours post dose on Day 1]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Tmax (0-12) Following BID Dosing of GSK2982772 in Part A [Pre-dose, 20 and 40 minutes, 1hour, 1 hour 30 minutes, 2, 3, 4, 6, 8, 10 hours and 12 hours post dose on Day 1]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Tmax (12-24) Following BID Dosing of GSK2982772 in Part A [12 hours, 12 hours 20 and 40 minutes, 13 hours, 13 hours 30 minutes, 14, 15, 16, 19, 22 and 24 hours post dose on Day 1]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Tmax (0-7) Following TID Dosing of GSK2982772 Part B [Pre-dose, 20 and 40 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 5, 7 hours post dose on Days 1 and 14]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Tmax (7-14) Following TID Dosing of GSK2982772 in Part B [7hours and 7 hours 20 and 40 minutes, 8hours, 8 hours 30 minutes, 9, 10, 12, 14 hours post dose on Day 14]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Tmax (14-24) Following TID Dosing of GSK2982772 in Part B [14hours, 14 hours 20 and 40 minutes, 15 hours and 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours post dose on Day 14]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Observed Trough Plasma Drug Concentration at 7 Hour (C7),Following TID Dosing of GSK2982772 in Part A [7 hours post-dose on Day 1]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Observed Trough Plasma Drug Concentration at 14 Hours (C14) Following TID Dosing of GSK2982772 in Part A [14 hours post-dose on Day 1]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
C24 Following TID Dosing of GSK2982772 in Part A [24 hours post-dose on Day 1]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
C12 Following BID Dosing of GSK2982772 in Part A [12 hours post-dose on Day 1]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
C24 Following BID Dosing of GSK2982772 in Part A [24 hours post-dose on Day 1]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
C0 Following TID Dosing of GSK2982772 in Part B [Pre-dose on Day 14]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
C7 Following TID Dosing of GSK2982772 in Part B [7 hours post-dose on Days 1 and 14]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
C14 Following TID Dosing of GSK2982772 in Part B [14 hours post-dose on Day 14]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
C24 Following TID Dosing of GSK2982772 in Part B [24 hours post-dose on Day 14]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
AUC([0-7] Following TID Dosing of GSK2982772 in Fed State of Part B [Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 9 and 11]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Cmax (0-7) Following TID Dosing of GSK2982772 in Fed State of Part B [Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 9 and 11]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Tmax (0-7) Following TID Dosing of GSK2982772 in Fed State of Part B [Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 9 and 11]
Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Ratio of Plasma 4 Beta-hydroxycholesterol to Cholesterol: Part B [Pre-dose on Day 1 and 24 hours post first dose on Day 14]
Blood samples were collected into EDTA tubes and processed to plasma for 4 beta-hydroxycholesterol and cholesterol. Ratio of 4 beta-hydroxycholesterol to cholesterol is presented

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Subject must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, neurological examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the Investigator in consultation with the Medical Monitor (if required) agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
Body weight >=50 kilograms (kg) and body mass index (BMI) within the range 19 - 30 kg per square meter (kg/m^2) (inclusive).
A male subject with a female partner of reproductive potential must agree to use contraception during the treatment period and for at least 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 at least one of the following conditions applies: not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance for a minimum of 28 days prior to the treatment period and for at least 30 days after the last administration of study drug. A WOCBP using a hormonal method of highly effective contraception must also agree to partner use of a male condom during the treatment period and for at least 30 days after the last administration of study drug.
Capable of giving signed informed consent.

Exclusion Criteria:

History or presence 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 of herpes zoster (shingles) reactivation.
Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest x-rays (posterior anterior and lateral), and TB testing: either a positive tuberculin skin test (TST; defined as a skin induration >5 millimeter (mm) at 48 to 72 hours, regardless of Bacillus Calmette-Guerin (BCG) or other vaccination history) or a positive (not indeterminate) QuantiFERON-TB Gold test.
ALT >1.5 times upper limit of normal (ULN).
Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
ECG QT interval corrected for heart rate (QTc) >450 millisecond (msec).
History of serious or recurrent infections or has had an active infection within 14 days of receiving study medication.
History of diagnosis of obstructive sleep apnoea or significant respiratory disorder. Childhood asthma that has fully resolved is permitted.
Part A: History of active suicidal ideation behavior (SIB) within the past 6 months or any history of attempted suicide in a subject's lifetime.
History of current evidence of febrile seizures, epilepsy, convulsions, significant head injury, or other significant neurologic conditions.
Past or intended use of over-the-counter or prescription medication, including herbal medications, within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is the longest) prior to dosing.
Subject received a vaccine (either live attenuated or now-live) within 30 days prior to randomization, or plans to receive a live attenuated vaccine within 30 days + 5 half-lives (32 days) of the last dose of study medication.
Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (mL) within a 56-day period.
Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Presence of Hepatitis B surface antigen (HBsAg) at screening Positive Hepatitis C antibody test result at screening.
Positive pre-study drug/alcohol screen.
Positive human immunodeficiency virus (HIV1 and 2) antibody test.
Regular use of known drugs of abuse.
Subjects with impaired renal function defined as Chronic Kidney Disease Epidemiology Collaboration (CKS-EPI) Creatinine > 1.6 mg/deciliter (mg/dL) with an age appropriate glomerular filtration rate (GFR) <= 60 (mL/minute/1.73 m^2) estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
An elevated C-reactive protein (CRP) outside of the normal reference range.
Regular alcohol consumption within 6 months prior to the study defined as: For United Kingdom (UK) - an average weekly intake of >14 units for males and females. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
Cotinine or carbon monoxide levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
Unwilling or unable to swallow multiple size 00 capsules as part of study participation.

PART B Specific exclusion criteria:

History of SIB as measured using the Columbia Suicide Severity Rating Scale (C-SSRS) or a history of attempted suicide.
A positive anti-nuclear antibody (ANA) outside of the normal reference range.
Fasting total cholesterol >=300 mg/dL or triglycerides >=250 mg/dL.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Cambridge		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:

NCT03305419

Other Study ID Numbers:

205184
2017-002662-45

First Posted:

Oct 10, 2017

Last Update Posted:

Nov 1, 2019

Last Verified:

Oct 1, 2019

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

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

Keywords provided by GlaxoSmithKline

Additional relevant MeSH terms:

Autoimmune Diseases

Study Results

Participant Flow

Recruitment Details	This study consisted of two parts; part A was single ascending dose, 3-way crossover and part B was repeat dose, sequential assignment which investigated the safety, tolerability, and pharmacokinetics of GSK2982772, in healthy participants.
Pre-assignment Detail	A total of 62 participants (15 in Part A and 47 in Part B) were enrolled in the study. Participants were not enrolled into the GSK2982772 360 milligram (mg) twice daily (BID) arm of Part B as one participant in the 360 mg BID dose level in Part A exceeded the maximum concentration (Cmax) stopping criteria.

Arm/Group Title	Part A:GSK2982772 120 mg TID/240 mg TID/360 mg BID	Part A:GSK2982772 120 mg TID/240 mg TID/Placebo	Part A:GSK2982772 120 mg TID/Placebo/GSK2982772 360 mg BID	Part A:Placebo/GSK2982772 240 mg TID/360 mg BID	Part B:Placebo	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID	Part B:GSK2982772 360 mg BID
Arm/Group Description	Participants received oral capsule of 120 mg GSK2982772 TID in treatment period 1 followed by 240 mg TID in treatment period 2 followed by 360 mg BID in treatment period 3. The treatment periods were separated by a washout period of at least 7 days.	Participants received oral capsule of 120 mg GSK2982772 TID in treatment period 1 followed by 240 mg TID in treatment period 2 followed by matching Placebo in treatment period 3. The treatment periods were separated by a washout period of at least 7 days.	Participants received oral capsule of 120 mg GSK2982772 TID in treatment period 1 followed by matching Placebo in treatment period 2 followed by 360 mg GSK2982772 BID in treatment period 3. The treatment periods were separated by a washout period of at least 7 days.	Participants received oral capsule of matching Placebo in treatment period 1 followed by 240 mg GSK2982772 TID in treatment period 2 followed by 360 mg GSK2982772 BID in treatment period 3. The treatment periods were separated by a washout period of at least 7 days.	Participants received matching oral placebo capsule to GSK2928772 for 14 days.	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.	Participants were planned to receive GSK2982772 oral capsule at a dose of 360 mg BID for 14 days.
Period Title: Part A Period 1 (1Day) + Washout (7days)
STARTED	3	3	3	3	0	0	0	0
COMPLETED	3	2	3	3	0	0	0	0
NOT COMPLETED	0	1	0	0	0	0	0	0
Period Title: Part A Period 1 (1Day) + Washout (7days)
STARTED	3	3	3	3	0	0	0	0
COMPLETED	1	3	3	3	0	0	0	0
NOT COMPLETED	2	0	0	0	0	0	0	0
Period Title: Part A Period 1 (1Day) + Washout (7days)
STARTED	3	3	3	3	0	0	0	0
COMPLETED	3	3	3	3	0	0	0	0
NOT COMPLETED	0	0	0	0	0	0	0	0
Period Title: Part A Period 1 (1Day) + Washout (7days)
STARTED	0	0	0	0	14	20	13	0
COMPLETED	0	0	0	0	11	10	8	0
NOT COMPLETED	0	0	0	0	3	10	5	0

Baseline Characteristics

Arm/Group Title	Part A:GSK2982772 120 mg TID/240 mg TID/360 mg BID	Part A:GSK2982772 120 mg TID/240 mg TID/Placebo	Part A:GSK2982772 120 mg TID/Placebo/GSK2982772 360 mg BID	Part A:Placebo/GSK2982772 240 mg TID/360 mg BID	Part B:Placebo	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID	Part B:GSK2982772 360 mg TID	Total
Arm/Group Description	Participants received oral capsule of 120 mg GSK2982772 three times a day in treatment period 1 followed by 240 mg TID in treatment period 2 followed by 360 mg BID in treatment period 3. The treatment periods were separated by a washout period of at least 7 days.	Participants received oral capsule of 120 mg GSK2982772 TID in treatment period 1 followed by 240 mg TID in treatment period 2 followed by matching Placebo in treatment period 3. The treatment periods were separated by a washout period of at least 7 days.	Participants received oral capsule of 120 mg GSK2982772 TID in treatment period 1 followed by matching Placebo in treatment period 2 followed by 360 mg GSK2982772 BID in treatment period 3. The treatment periods were separated by a washout period of at least 7 days.	Participants received oral capsule of matching Placebo in treatment period 1 followed by 240 mg GSK2982772 TID in treatment period 2 followed by 360 mg GSK2982772 BID in treatment period 3. The treatment periods were separated by a washout period of at least 7 days.	Participants received matching oral placebo capsule to GSK2928772 for 14 days.	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.	Participants received GSK2982772 oral capsule at a dose of 360 mg TID for 14 days.	Total of all reporting groups
Overall Participants	5	4	3	3	14	20	13	0	62
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	36.2 (9.04)	42.5 (9.95)	59.0 (3.61)	49.0 (10.00)	39.1 (9.66)	43.3 (10.87)	38.6 (11.03)	45.25 (9.16)
Sex: Female, Male (Count of Participants)
Female	2 40%	2 50%	1 33.3%	0 0%	0 0%	0 0%	0 0%	0 NaN	5 8.1%
Male	3 60%	2 50%	2 66.7%	3 100%	14 100%	20 100%	13 100%	0 NaN	57 91.9%
Race/Ethnicity, Customized (Number) [Number]
Black or African American	0 0%	1 25%	1 33.3%	0 0%	0 0%	1 5%	3 23.1%	6 Infinity
Asian - East Asian Heritage	0 0%	0 0%	0 0%	0 0%	1 7.1%	0 0%	0 0%	1 Infinity
Asian - Japanese Heritage	0 0%	0 0%	0 0%	0 0%	1 7.1%	0 0%	0 0%	1 Infinity
White - White/Caucasian/European Herit	5 100%	3 75%	2 66.7%	3 100%	12 85.7%	19 95%	10 76.9%	54 Infinity

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Adverse Events (AEs) and Serious AEs (SAEs): Part A
Description	An AE is any untoward medical occurrence in a clinical study subjects, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE.
Time Frame	Up to Day 14

Outcome Measure Data

Analysis Population Description
Safety population. Safety population consists of all randomized participants who take at least 1 dose of study treatment.

Arm/Group Title	Part A:Placebo	Part A:GSK2982772 120 mg TID	Part A:GSK2982772 240 mg TID	Part A:GSK2982772 360 mg BID
Arm/Group Description	Participants received matching oral placebo capsule to GSK2928772	Participants received GSK2982772 oral capsule at a dose of 120 mg TID	Participants received GSK2982772 oral capsule at a dose of 240 mg TID	Participants received GSK2982772 oral capsule at a dose of 360 mg BID
Measure Participants	9	9	9	9
AEs	3 60%	6 150%	4 133.3%	7 233.3%
SAEs	0 0%	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Number of Participants With AEs and SAEs: Part B
Description	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE.
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description
Safety population. GSK2982772 360 mg BID was not started in Part B as one participant in GSK2982772 360 mg BID of Part A exceeded the Cmax stopping criteria

Arm/Group Title	Part B:Placebo	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID	Part B:GSK2982772 360 mg BID
Arm/Group Description	Participants received matching oral placebo capsule to GSK2928772 for 14 days	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.	Participants were planned to receive GSK2982772 oral capsule at a dose of 360 mg BID for 14 days
Measure Participants	14	20	13	0
AEs	9 180%	17 425%	12 400%
SAEs	1 20%	0 0%	0 0%

3. Primary Outcome

Title	Number of Participants With Worst Case Clinical Chemistry Parameters by Potential Clinical Importance Criteria: Part A
Description	Blood samples were collected from participants for the analysis of following clinical chemistry parameters: alanine amino transferase (ALT), albumin, alkaline phosphatase, aspartate amino transferase (AST), calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were >=2 times Upper Limit of Normal (ULN) units per liter (U/L) for ALT, <30 grams per liter (g/L) for albumin, >=2 times ULN U/L for alkaline phosphatase, >=2 times ULN U/L for AST, <2 or >2.75 millimoles per liter (mmol/L) for calcium, >44.2 micromoles per liter (µmol/L) for creatinine, <3 or >9 mmol/L for glucose, <3 or >5.5 mmol/L for potassium, <130 or >150 mmol/L for sodium and >=1.5 times ULN for total bilirubin. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Time Frame	Up to Week 9

Outcome Measure Data

Analysis Population Description
Safety population

Arm/Group Title	Part A:Placebo	Part A:GSK2982772 120 mg TID	Part A:GSK2982772 240 mg TID	Part A:GSK2982772 360 mg BID
Arm/Group Description	Participants received matching oral placebo capsule to GSK2928772	Participants received GSK2982772 oral capsule at a dose of 120 mg TID	Participants received GSK2982772 oral capsule at a dose of 240 mg TID	Participants received GSK2982772 oral capsule at a dose of 360 mg BID
Measure Participants	9	9	9	9
ALT, Low	0 0%	0 0%	0 0%	0 0%
ALT, No change	9 180%	9 225%	9 300%	9 300%
ALT, High	0 0%	0 0%	0 0%	0 0%
Albumin, Low	0 0%	0 0%	0 0%	0 0%
Albumin, No change	9 180%	9 225%	9 300%	9 300%
Albumin, High	0 0%	0 0%	0 0%	0 0%
Alkaline phosphatase, Low	0 0%	0 0%	0 0%	0 0%
Alkaline phosphatase, No change	9 180%	9 225%	9 300%	9 300%
Alkaline phosphatase, High	0 0%	0 0%	0 0%	0 0%
AST, Low	0 0%	0 0%	0 0%	0 0%
AST, No change	9 180%	9 225%	9 300%	9 300%
AST, High	0 0%	0 0%	0 0%	0 0%
Calcium, Low	0 0%	0 0%	0 0%	0 0%
Calcium, No change	9 180%	9 225%	9 300%	9 300%
Calcium, High	0 0%	0 0%	0 0%	0 0%
Creatinine, Low	0 0%	0 0%	0 0%	0 0%
Creatinine, No change	9 180%	9 225%	9 300%	9 300%
Creatinine, High	0 0%	0 0%	0 0%	0 0%
Glucose, Low	0 0%	0 0%	0 0%	0 0%
Glucose, No change	9 180%	9 225%	9 300%	9 300%
Glucose, High	0 0%	0 0%	0 0%	0 0%
Potassium, Low	0 0%	0 0%	0 0%	0 0%
Potassium, No change	9 180%	9 225%	9 300%	9 300%
Potassium, High	0 0%	0 0%	0 0%	0 0%
Sodium, Low	0 0%	0 0%	0 0%	0 0%
Sodium, No change	9 180%	9 225%	9 300%	9 300%
Sodium, High	0 0%	0 0%	0 0%	0 0%
Total Bilirubin, Low	0 0%	0 0%	0 0%	0 0%
Total Bilirubin, No change	9 180%	9 225%	9 300%	9 300%
Total Bilirubin, High	0 0%	0 0%	0 0%	0 0%

4. Primary Outcome

Title	Number of Participants With Worst Case Clinical Chemistry Parameters by Potential Clinical Importance Criteria: Part B
Description	Blood samples were collected from participants for the analysis of following clinical chemistry parameters: ALT, albumin, alkaline phosphatase, AST, calcium, creatinine, glucose, potassium, sodium and total bilirubin. PCI ranges were >=2 times ULN U/L for ALT, <30 g/L for albumin, >=2 times ULN U/L for alkaline phosphatase, >=2 times ULN U/L for AST, <2 or >2.75 mmol/L for calcium, >44.2 µmol/L for creatinine, <3 or >9 mmol/L for glucose, <3 or >5.5 mmol/L for potassium, <130 or >150 mmol/L for sodium and >=1.5 times ULN for total bilirubin. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Time Frame	Up to Week 4

Outcome Measure Data

Analysis Population Description
Safety population. GSK2982772 360 mg BID of Part B was not started as one participant in GSK2982772 360 mg BID of Part A exceeded the Cmax stopping criteria

Arm/Group Title	Part B:Placebo	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID	Part B:GSK2982772 360 mg BID
Arm/Group Description	Participants received matching oral placebo capsule to GSK2928772 for 14 days	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.	Participants were planned to receive GSK2982772 oral capsule at a dose of 360 mg BID for 14 days
Measure Participants	14	20	13	0
ALT, Low	0 0%	0 0%	0 0%
ALT, No change	14 280%	19 475%	13 433.3%
ALT, High	0 0%	1 25%	0 0%
Albumin, Low	0 0%	0 0%	0 0%
Albumin, No change	14 280%	20 500%	13 433.3%
Albumin, High	0 0%	0 0%	0 0%
Alkaline phosphatase, Low	0 0%	0 0%	0 0%
Alkaline phosphatase, No change	14 280%	20 500%	13 433.3%
Alkaline phosphatase, High	0 0%	0 0%	0 0%
AST, Low	0 0%	0 0%	0 0%
AST, No change	14 280%	19 475%	13 433.3%
AST, High	0 0%	1 25%	0 0%
Calcium, Low	0 0%	0 0%	0 0%
Calcium, No change	14 280%	20 500%	13 433.3%
Calcium, High	0 0%	0 0%	0 0%
Creatinine, Low	0 0%	0 0%	0 0%
Creatinine, No change	14 280%	20 500%	13 433.3%
Creatinine, High	0 0%	0 0%	0 0%
Glucose, Low	0 0%	0 0%	0 0%
Glucose, No change	14 280%	20 500%	13 433.3%
Glucose, High	0 0%	0 0%	0 0%
Potassium, Low	0 0%	0 0%	0 0%
Potassium, No change	14 280%	20 500%	12 400%
Potassium, High	0 0%	0 0%	1 33.3%
Sodium, Low	0 0%	0 0%	0 0%
Sodium, No change	14 280%	20 500%	13 433.3%
Sodium, High	0 0%	0 0%	0 0%
Total Bilirubin, Low	0 0%	0 0%	0 0%
Total Bilirubin, No change	14 280%	20 500%	13 433.3%
Total Bilirubin, High	0 0%	0 0%	0 0%

5. Primary Outcome

Title	Number of Participants With Worst Case Hematology Parameters by Potential Clinical Importance Criteria: Part A
Description	Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, lymphocytes, platelet count, total neutrophils and white blood cell (WBC) counts. PCI ranges were >0.54 or < 0.075 proportion of red blood cells (RBC) in blood for hematocrit, <25 or >180 g/L for hemoglobin, 0.8 x10^9 cells/L for lymphocytes, <1.5 x10^9 cells/L for neutrophils, <100 or >550 x10^9 cells/L for platelets and <3 or 20> x 10^9 cells per liter WBC. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Time Frame	Up to Week 9

Outcome Measure Data

Analysis Population Description
Safety population.

Arm/Group Title	Part A:Placebo	Part A:GSK2982772 120 mg TID	Part A:GSK2982772 240 mg TID	Part A:GSK2982772 360 mg BID
Arm/Group Description	Participants received matching oral placebo capsule to GSK2928772	Participants received GSK2982772 oral capsule at a dose of 120 mg TID	Participants received GSK2982772 oral capsule at a dose of 240 mg TID	Participants received GSK2982772 oral capsule at a dose of 360 mg BID
Measure Participants	9	9	9	9
Hematocrit, Low	0 0%	0 0%	0 0%	0 0%
Hematocrit, No change	9 180%	9 225%	9 300%	9 300%
Hematocrit, High	0 0%	0 0%	0 0%	0 0%
Hemoglobin, Low	0 0%	0 0%	0 0%	0 0%
Hemoglobin, No change	9 180%	9 225%	9 300%	9 300%
Hemoglobin, High	0 0%	0 0%	0 0%	0 0%
Lymphocytes, Low	0 0%	0 0%	0 0%	0 0%
Lymphocytes, No change	9 180%	9 225%	9 300%	9 300%
Lymphocytes, High	0 0%	0 0%	0 0%	0 0%
Platelet count, Low	0 0%	0 0%	0 0%	0 0%
Platelet, No change	9 180%	9 225%	9 300%	9 300%
Platelet, High	0 0%	0 0%	0 0%	0 0%
Total Neutrophils, Low	1 20%	0 0%	0 0%	0 0%
Total Neutrophils, No change	8 160%	9 225%	9 300%	9 300%
Total Neutrophils, High	0 0%	0 0%	0 0%	0 0%
WBC count, Low	0 0%	0 0%	0 0%	0 0%
WBC, No change	9 180%	9 225%	9 300%	9 300%
WBC, High	0 0%	0 0%	0 0%	0 0%

6. Primary Outcome

Title	Number of Participants With Worst Case Hematology Parameters by Potential Clinical Importance Criteria: Part B
Description	Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, lymphocytes, platelet count, total neutrophils and WBC counts. PCI ranges were >0.54 or < 0.075 proportion of RBC in blood for hematocrit, <25 or >180 g/L for hemoglobin, 0.8 x10^9 cells/L for lymphocytes, <1.5 x10^9 cells/L for neutrophils, <100 or >550 x10^9 cells/L for platelets and <3 or 20> x 10^9 cells per liter WBC. Participants were counted in the worst case category that their value changed to low, normal or high. If values were unchanged (example: High to High), or whose value became normal, were recorded in 'No Change' category.
Time Frame	Up to Week 4

Outcome Measure Data

Analysis Population Description
Safety population. GSK2982772 360 mg BID of Part B was not started as one participant in GSK2982772 360 mg BID of Part A exceeded the Cmax stopping criteria

Arm/Group Title	Part B:Placebo	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID	Part B:GSK2982772 360 mg BID
Arm/Group Description	Participants received matching oral placebo capsule to GSK2928772 for 14 days	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.	Participants were planned to receive GSK2982772 oral capsule at a dose of 360 mg BID for 14 days
Measure Participants	14	20	13	0
Hematocrit, Low	0 0%	0 0%	0 0%
Hematocrit, No change	14 280%	20 500%	13 433.3%
Hematocrit, High	0 0%	0 0%	0 0%
Hemoglobin, Low	0 0%	0 0%	0 0%
Hemoglobin, No change	14 280%	20 500%	13 433.3%
Hemoglobin, High	0 0%	0 0%	0 0%
Lymphocytes, Low	0 0%	0 0%	1 33.3%
Lymphocytes, No change	14 280%	20 500%	12 400%
Lymphocytes, High	0 0%	0 0%	0 0%
Platelet count, Low	0 0%	0 0%	0 0%
Platelet, No change	14 280%	20 500%	13 433.3%
Platelet, High	0 0%	0 0%	0 0%
Total Neutrophils, Low	0 0%	1 25%	3 100%
Total Neutrophils, No change	14 280%	19 475%	10 333.3%
Total Neutrophils, High	0 0%	0 0%	0 0%
WBC count, Low	0 0%	0 0%	0 0%
WBC, No change	14 280%	20 500%	13 433.3%
WBC, High	0 0%	0 0%	0 0%

7. Primary Outcome

Title	Number of Participants With Worst Case Urinalysis Results: Part A
Description	Urine samples were collected from participants for analysis of following parameters: cellular casts, granular casts, hyaline casts, RBC and WBC and were counted as cells per high-power field (cells/HPF). The number of participants with cells in urine has been presented.
Time Frame	Up to Week 9

Outcome Measure Data

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

Arm/Group Title	Part A:Placebo	Part A:GSK2982772 120 mg TID	Part A:GSK2982772 240 mg TID	Part A:GSK2982772 360 mg BID
Arm/Group Description	Participants received matching oral placebo capsule to GSK2928772	Participants received GSK2982772 oral capsule at a dose of 120 mg TID	Participants received GSK2982772 oral capsule at a dose of 240 mg TID	Participants received GSK2982772 oral capsule at a dose of 360 mg BID
Measure Participants	3	1	1	1
Cellular casts, No change	3 60%	1 25%	1 33.3%	1 33.3%
Cellular casts, Any increase	0 0%	0 0%	0 0%	0 0%
Cellular casts, Increase to 1-9/HPF	0 0%	0 0%	0 0%	0 0%
Cellular casts, Increase to 10-50/HPF	0 0%	0 0%	0 0%	0 0%
Granular casts, No change	3 60%	1 25%	1 33.3%	1 33.3%
Granular casts, Any increase	0 0%	0 0%	0 0%	0 0%
Granular casts, Increase 1-9/HPF	0 0%	0 0%	0 0%	0 0%
Granular casts, Increase 10-50/HPF	0 0%	0 0%	0 0%	0 0%
Hyaline casts, No change	3 60%	1 25%	1 33.3%	1 33.3%
Hyaline casts, Any increase	0 0%	0 0%	0 0%	0 0%
Hyaline casts, Increase 1-9/HPF	0 0%	0 0%	0 0%	0 0%
Hyaline casts, Increase 10-50/HPF	0 0%	0 0%	0 0%	0 0%
RBC, No change	3 60%	0 0%	1 33.3%	0 0%
RBC, Any increase	0 0%	1 25%	0 0%	1 33.3%
RBC, Increase 1-9/HPF	0 0%	1 25%	0 0%	1 33.3%
RBC, Increase 10-50/HPF	0 0%	0 0%	0 0%	0 0%
WBC, No change	3 60%	1 25%	1 33.3%	0 0%
WBC, Any increase	0 0%	0 0%	0 0%	1 33.3%
WBC, Increase 1-9/HPF	0 0%	0 0%	0 0%	1 33.3%
WBC, Increase 10-50/HPF	0 0%	0 0%	0 0%	0 0%

8. Primary Outcome

Title	Number of Participants With Worst Case Urinalysis Results: Part B
Description	Urine samples were collected from participants for analysis of following parameters: cellular casts, granular casts, hyaline casts, RBC and WBC and were counted as cells per high-power field (cells/HPF). The number of participants with cells in urine has been presented.
Time Frame	Up to Week 4

Outcome Measure Data

Analysis Population Description
Safety population. GSK2982772 360 mg BID of Part B was not started as one participant in GSK2982772 360 mg BID of Part A exceeded the Cmax stopping criteria. Only those participants with data available at specified timepoints were analyzed.

Arm/Group Title	Part B:Placebo	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID	Part B:GSK2982772 360 mg BID
Arm/Group Description	Participants received matching oral placebo capsule to GSK2928772 for 14 days	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.	Participants were planned to receive GSK2982772 oral capsule at a dose of 360 mg BID for 14 days
Measure Participants	0	7	2	0
Cellular casts, No change	7 140%	2 50%
Cellular casts, Any increase	0 0%	0 0%
Cellular casts, Increase to 1-9/HPF	0 0%	0 0%
Cellular casts, Increase to 10-50/HPF	0 0%	0 0%
Granular casts, No change	7 140%	2 50%
Granular casts, Any increase	0 0%	0 0%
Granular casts, Increase 1-9/HPF	0 0%	0 0%
Granular casts, Increase 10-50/HPF	0 0%	0 0%
Hyaline casts, No change	7 140%	2 50%
Hyaline casts, Any increase	0 0%	0 0%
Hyaline casts, Increase 1-9/HPF	0 0%	0 0%
Hyaline casts, Increase 10-50/HPF	0 0%	0 0%
RBC, No change	5 100%	1 25%
RBC, Any increase	2 40%	1 25%
RBC, Increase 1-9/HPF	2 40%	1 25%
RBC, Increase 10-50/HPF	0 0%	0 0%
WBC, No change	5 100%	2 50%
WBC, Any increase	2 40%	0 0%
WBC, Increase 1-9/HPF	2 40%	0 0%
WBC, Increase 10-50/HPF	0 0%	0 0%

9. Primary Outcome

Title	Number of Participants With Abnormal Vital Signs: Part A
Description	Vital signs were measured in a supine position after 5 minutes rest. The PCI criteria for vital signs included: systolic blood pressure <85 and >160 millimeters of mercury [mmHg]), diastolic blood pressure <45 mmHg and >100 mmHg, heart rate <40 and >100 beats per minute, body temperature <=35.5 and >=37.8 degrees Celsius and respiration rate <=8 and >=20 breaths per minute. Data of participants with potential clinical importance has been reported.
Time Frame	Up to Week 9

Outcome Measure Data

Analysis Population Description
Safety population

Arm/Group Title	Part A:Placebo	Part A:GSK2982772 120 mg TID	Part A:GSK2982772 240 mg TID	Part A:GSK2982772 360 mg BID
Arm/Group Description	Participants received matching oral placebo capsule to GSK2928772	Participants received GSK2982772 oral capsule at a dose of 120 mg TID	Participants received GSK2982772 oral capsule at a dose of 240 mg TID	Participants received GSK2982772 oral capsule at a dose of 360 mg BID
Measure Participants	9	9	9	9
Count of Participants [Participants]	6 120%	8 200%	7 233.3%	8 266.7%

10. Primary Outcome

Title	Number of Participants With Abnormal Vital Signs: Part B
Description	Vital signs were measured in a supine position after 5 minutes rest. The PCI criteria for vital signs included: systolic blood pressure <85 and >160 mmHg, diastolic blood pressure <45 mmHg and >100 mmHg, heart rate <40 and >100 beats per minute, body temperature <=35.5 and >=37.8 degrees Celsius and respiration rate <=8 and >=20 breaths per minute. Data of participants with potential clinical importance has been reported.
Time Frame	Up to Week 4

Outcome Measure Data

Analysis Population Description
Safety population. GSK2982772 360 mg BID of Part B was not started as one participant in GSK2982772 360 mg BID of Part A exceeded the Cmax stopping criteria

Arm/Group Title	Part B:Placebo	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID	Part B:GSK2982772 360 mg BID
Arm/Group Description	Participants received matching oral placebo capsule to GSK2928772 for 14 days	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.	Participants were planned to receive GSK2982772 oral capsule at a dose of 360 mg BID for 14 days
Measure Participants	14	20	13	0
Count of Participants [Participants]	11 220%	20 500%	12 400%

11. Primary Outcome

Title	Number of Participants With Abnormal Electrocardiogram (ECG) Findings: Part A
Description	12-lead ECG's were obtained in the supine position after 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant and not clinically significant abnormal ECG findings have been presented. 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	Up to Day 4

Outcome Measure Data

Analysis Population Description
Safety population

Arm/Group Title	Part A:Placebo	Part A:GSK2982772 120 mg TID	Part A:GSK2982772 240 mg TID	Part A:GSK2982772 360 mg BID
Arm/Group Description	Participants received matching oral placebo capsule to GSK2928772	Participants received GSK2982772 oral capsule at a dose of 120 mg TID	Participants received GSK2982772 oral capsule at a dose of 240 mg TID	Participants received GSK2982772 oral capsule at a dose of 360 mg BID
Measure Participants	9	9	9	9
Abnormal, not clinically significant	1 20%	0 0%	2 66.7%	4 133.3%
Abnormal, clinically significant	0 0%	0 0%	0 0%	0 0%

12. Primary Outcome

Title	Number of Participants With Abnormal ECG Findings: Part B
Description	12-lead ECG's were obtained in the supine position after 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant and not clinically significant abnormal ECG findings have been presented. 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	Up to Week 4

Outcome Measure Data

Analysis Population Description
Safety population. GSK2982772 360 mg BID of Part B was not started as one participant in GSK2982772 360 mg BID of Part A exceeded the Cmax stopping criteria

Arm/Group Title	Part B:Placebo	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID	Part B:GSK2982772 360 mg BID
Arm/Group Description	Participants received matching oral placebo capsule to GSK2928772 for 14 days	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.	Participants were planned to receive GSK2982772 oral capsule at a dose of 360 mg BID for 14 days
Measure Participants	14	20	13	0
Abnormal, not clinically significant	3 60%	4 100%	3 100%
Abnormal, clinically significant	0 0%	0 0%	0 0%

13. Secondary Outcome

Title	Area Under the Concentration-time Curve (AUC) From Time Zero to 24 Hours (AUC[0-24]) Following TID Dosing of GSK2982772: Part A
Description	Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 20, 40minutes, 1 hour, 1hr 30min, 2, 3, 5, 7hour, 7hr 20min,and 7hr 40 min, 8hr, 8hr 30min, 9hr, 10hr, 12hr, 14hr, 14hr 20min, 14hr 40 min, 15hr, 15hr 30min, 16hr, 17hr, 19hr, 22hr, 24hours post dose on Day1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population. Pharmacokinetic population consists of participants in the safety population for whom a pharmacokinetic sample were obtained and analyzed.

Arm/Group Title	Part A:GSK2982772 120 mg TID	Part A:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID	Participants received GSK2982772 oral capsule at a dose of 240 mg TID
Measure Participants	9	9
Geometric Mean (Geometric Coefficient of Variation) [Hours*microgram per millilter]	21.22 (41.37)	46.13 (37.38)

14. Secondary Outcome

Title	AUC(0-24) Following BID Dosing of GSK2982772: Part A
Description	Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 20min, 40min, 1hr, 1hr 30min, 2hr, 3hr, 4hr, 6hr, 8hr, 10hr, 12hr, 12hr 20min, 12hr 40min, 13hr, 13hr 30min, 14hr, 15hr, 16hr, 19hr, 22hr, 24hr post dose on Day 1.

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population.

Arm/Group Title	Part A:GSK2982772 360 mg BID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 360 mg BID
Measure Participants	9
Geometric Mean (Geometric Coefficient of Variation) [Hours*microgram per millilter]	54.02 (36.02)

15. Secondary Outcome

Title	AUC[0-24] Following TID Dosing of GSK2982772: Part B
Description	Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 20, 40minutes, 1 hour, 1hr 30min, 2, 3, 5, 7hour, 7hr 20min,and 7hr 40 min, 8hr, 8hr 30min, 9hr, 10hr, 12hr, 14hr, 14hr 20min, 14hr 40 min, 15hr, 15hr 30min, 16hr, 17hr, 19hr, 22hr, 24hours post dose on Day14

Outcome Measure Data

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

Arm/Group Title	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.
Measure Participants	10	8
Geometric Mean (Geometric Coefficient of Variation) [Hours*microgram per millilter]	25.67 (28.81)	52.00 (45.26)

16. Secondary Outcome

Title	AUC (0-7) Following TID Dosing of GSK2982772 : Part A
Description	Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population

Arm/Group Title	Part A:GSK2982772 120 mg TID	Part A:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID	Participants received GSK2982772 oral capsule at a dose of 240 mg TID
Measure Participants	9	9
Geometric Mean (Geometric Coefficient of Variation) [Hours*microgram per millilter]	6.053 (33.87)	11.686 (33.50)

17. Secondary Outcome

Title	AUC (7-14) Following TID Dosing of GSK2982772 : Part A
Description	Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	7 hours, 7 hours 20 and 40 minutes, 8 hours, 8 hours 30 minutes, 9, 10, 12, 14 hours on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population

Arm/Group Title	Part A:GSK2982772 120 mg TID	Part A:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID	Participants received GSK2982772 oral capsule at a dose of 240 mg TID
Measure Participants	9	9
Geometric Mean (Geometric Coefficient of Variation) [Hours*microgram per millilter]	7.829 (44.25)	17.823 (42.11)

18. Secondary Outcome

Title	AUC (14-24) Following TID Dosing of GSK2982772 : Part A
Description	Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	14 hours, 14 hours 20 and 40 minutes, 15 hours ,15 hours 30 minutes, 16, 19, 22 and 24 hours on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population

Arm/Group Title	Part A:GSK2982772 120 mg TID	Part A:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID	Participants received GSK2982772 oral capsule at a dose of 240 mg TID
Measure Participants	9	9
Geometric Mean (Geometric Coefficient of Variation) [Hours*microgram per millilter]	7.213 (48.85)	16.300 (39.72)

19. Secondary Outcome

Title	AUC (0-12) Following BID Dosing of GSK2982772 in Part A
Description	Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 4, 6, 8, 10 hours,12 hours on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population

Arm/Group Title	Part A:GSK2982772 360 mg BID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 360 mg BID
Measure Participants	9
Geometric Mean (Geometric Coefficient of Variation) [Hours*microgram per millilter]	21.80 (24.41)

20. Secondary Outcome

Title	AUC (12-24) Following BID Dosing of GSK2982772 in Part A
Description	Blood samples were collected at indicated timepoints for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	12 hours, 12 hours 20 and 40 minutes, 13 and 13 hours 30 minutes, 14, 15, 16, 19, 22 and 24 hours on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population

Arm/Group Title	Part A:GSK2982772 360 mg BID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 360 mg BID
Measure Participants	9
Geometric Mean (Geometric Coefficient of Variation) [Hours*microgram per millilter]	31.69 (48.02)

21. Secondary Outcome

Title	AUC(0-7) Following TID Dosing of GSK2982772 in Part B
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 1 and 14

Outcome Measure Data

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

Arm/Group Title	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.
Measure Participants	20	13
AUC (0-7), Day 1, n=20, 13	6.550 (37.67)	11.895 (33.98)
AUC (0-7), Day 14, n=10, 9	7.485 (25.53)	14.835 (45.30)

22. Secondary Outcome

Title	AUC (7-14) Following TID Dosing of GSK2982772 in Part B
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	7 and 7 hours 20 and 40 minutes, 8 and 8 hours 30 minutes, 9, 10, 12, 14 hours on Day 14

Outcome Measure Data

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

Arm/Group Title	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.
Measure Participants	10	8
Geometric Mean (Geometric Coefficient of Variation) [Hours*microgram per millilter]	9.095 (30.57)	17.372 (34.96)

23. Secondary Outcome

Title	AUC (14-24) Following TID Dosing of GSK2982772 in Part B
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	14 hours, 14 hours 20 minutes, 14 hours 40 minutes, 15 hours, 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours on Day 14

Outcome Measure Data

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

Arm/Group Title	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.
Measure Participants	10	8
Geometric Mean (Geometric Coefficient of Variation) [Hours*microgram per millilter]	8.988 (33.57)	19.816 (55.60)

24. Secondary Outcome

Title	Maximum Observed Plasma Drug Concentration Cmax (0-7) Following TID Dosing of GSK2982772 in Part A
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, and 7 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population

Arm/Group Title	Part A:GSK2982772 120 mg TID	Part A:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID	Participants received GSK2982772 oral capsule at a dose of 240 mg TID
Measure Participants	9	9
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	1.7672 (41.78)	3.3125 (25.88)

25. Secondary Outcome

Title	Cmax (7-14) Following TID Dosing of GSK2982772 in Part A
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	7 hours, 7 hours 20 and 40 minutes, 8 and 8 hours 30 minutes, 9, 10, 12, 14 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population

Arm/Group Title	Part A:GSK2982772 120 mg TID	Part A:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID	Participants received GSK2982772 oral capsule at a dose of 240 mg TID
Measure Participants	9	9
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	2.148 (36.24)	5.007 (33.09)

26. Secondary Outcome

Title	Cmax (14-24) Following TID Dosing of GSK2982772 in Part A
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	14 hours, 14 hours 20 and 40 minutes, 15 and 15 hours 30 minutes, 16, 19, 22 and 24 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population

Arm/Group Title	Part A:GSK2982772 120 mg TID	Part A:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID	Participants received GSK2982772 oral capsule at a dose of 240 mg TID
Measure Participants	9	9
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	1.4156 (47.03)	3.4812 (28.46)

27. Secondary Outcome

Title	Cmax (0-12) Following BID Dosing of GSK2982772 in Part A
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 4, 6, 8, 10 hours and 12 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population

Arm/Group Title	Part A:GSK2982772 360 mg BID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 360 mg BID
Measure Participants	9
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	4.967 (30.75)

28. Secondary Outcome

Title	Cmax (12-24) Following BID Dosing of GSK2982772 in Part A
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	12 hours, 12 hours 20 and 40 minutes, 13 and 13 hours 30 minutes, 14, 15, 16, 19, 22 and 24 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population

Arm/Group Title	Part A:GSK2982772 360 mg BID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 360 mg BID
Measure Participants	9
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	6.965 (61.70)

29. Secondary Outcome

Title	Cmax (0-7) Following TID Dosing of GSK2982772 in Part B
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours post dose on Days 1 and 14

Outcome Measure Data

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

Arm/Group Title	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.
Measure Participants	20	13
Cmax (0-7), Day 1, n=20, 13	2.0883 (37.87)	3.2333 (37.04)
Cmax (0-7), Day 14, n=10, 9	2.2239 (30.03)	4.3784 (45.62)

30. Secondary Outcome

Title	Cmax (7-14) Following TID Dosing of GSK2982772 in Part B
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	7hours, 7 hours 20 and 40 minutes, 8 hours, 8 hours 30 minutes, 9, 10, 12, 14 hours on Day 14

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population.

Arm/Group Title	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.
Measure Participants	10	8
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	2.505 (26.70)	5.435 (32.59)

31. Secondary Outcome

Title	Cmax (14-24) Following TID Dosing of GSK2982772 in Part B
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	14 hours, 14 hours 20 and 40 minutes, 15 hours, 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours post dose on Day 14

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population.

Arm/Group Title	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.
Measure Participants	10	8
Geometric Mean (Geometric Coefficient of Variation) [Microgram per millilter]	1.9205 (30.82)	4.1607 (38.79)

32. Secondary Outcome

Title	Time to Cmax (Tmax) (0-7) Following TID Dosing of GSK2982772 in Part A
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, and 7 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population.

Arm/Group Title	Part A:GSK2982772 120 mg TID	Part A:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID	Participants received GSK2982772 oral capsule at a dose of 240 mg TID
Measure Participants	9	9
Median (Full Range) [Hours]	3.008	2.043

33. Secondary Outcome

Title	Tmax (7-14) Following TID Dosing of GSK2982772 in Part A
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	7hours, 7 hours 20 and 40 minutes, 8 hours, 8 hours 30 minutes, 9, 10, 12, 14 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population.

Arm/Group Title	Part A:GSK2982772 120 mg TID	Part A:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID	Participants received GSK2982772 oral capsule at a dose of 240 mg TID
Measure Participants	9	9
Median (Full Range) [Hours]	10.000	9.000

34. Secondary Outcome

Title	Tmax (14-24) Following TID Dosing of GSK2982772 in Part A
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	14 hours, 14 hours 20 and 40 minutes, 15 hours, 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population.

Arm/Group Title	Part A:GSK2982772 120 mg TID	Part A:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID	Participants received GSK2982772 oral capsule at a dose of 240 mg TID
Measure Participants	9	9
Median (Full Range) [Hours]	19.00	17.02

35. Secondary Outcome

Title	Tmax (0-12) Following BID Dosing of GSK2982772 in Part A
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 20 and 40 minutes, 1hour, 1 hour 30 minutes, 2, 3, 4, 6, 8, 10 hours and 12 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population.

Arm/Group Title	Part A:GSK2982772 360 mg BID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 360 mg BID
Measure Participants	9
Median (Full Range) [Hours]	3.000

36. Secondary Outcome

Title	Tmax (12-24) Following BID Dosing of GSK2982772 in Part A
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	12 hours, 12 hours 20 and 40 minutes, 13 hours, 13 hours 30 minutes, 14, 15, 16, 19, 22 and 24 hours post dose on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population.

Arm/Group Title	Part A:GSK2982772 360 mg BID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 360 mg BID
Measure Participants	9
Median (Full Range) [Hours]	14.01

37. Secondary Outcome

Title	Tmax (0-7) Following TID Dosing of GSK2982772 Part B
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 20 and 40 minutes, 1 hour, 1 hour 30 minutes, 2, 3, 5, 7 hours post dose on Days 1 and 14

Outcome Measure Data

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

Arm/Group Title	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.
Measure Participants	20	13
Tmax (0-7), Day 1, n=20, 13	2.000	3.000
Tmax (0-7), Day 14, n=10, 9	1.750	2.003

38. Secondary Outcome

Title	Tmax (7-14) Following TID Dosing of GSK2982772 in Part B
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	7hours and 7 hours 20 and 40 minutes, 8hours, 8 hours 30 minutes, 9, 10, 12, 14 hours post dose on Day 14

Outcome Measure Data

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

Arm/Group Title	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.
Measure Participants	10	8
Median (Full Range) [Hours]	9.001	10.008

39. Secondary Outcome

Title	Tmax (14-24) Following TID Dosing of GSK2982772 in Part B
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	14hours, 14 hours 20 and 40 minutes, 15 hours and 15 hours 30 minutes, 16, 17, 19, 22 and 24 hours post dose on Day 14

Outcome Measure Data

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

Arm/Group Title	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.
Measure Participants	10	8
Median (Full Range) [Hours]	17.02	18.92

40. Secondary Outcome

Title	Observed Trough Plasma Drug Concentration at 7 Hour (C7),Following TID Dosing of GSK2982772 in Part A
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	7 hours post-dose on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population

Arm/Group Title	Part A:GSK2982772 120 mg TID	Part A:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID	Participants received GSK2982772 oral capsule at a dose of 240 mg TID
Measure Participants	9	9
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	0.3614 (84.67)	0.7723 (89.30)

41. Secondary Outcome

Title	Observed Trough Plasma Drug Concentration at 14 Hours (C14) Following TID Dosing of GSK2982772 in Part A
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	14 hours post-dose on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population

Arm/Group Title	Part A:GSK2982772 120 mg TID	Part A:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID	Participants received GSK2982772 oral capsule at a dose of 240 mg TID
Measure Participants	9	9
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	0.4318 (86.28)	0.7487 (76.95)

42. Secondary Outcome

Title	C24 Following TID Dosing of GSK2982772 in Part A
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	24 hours post-dose on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population

Arm/Group Title	Part A:GSK2982772 120 mg TID	Part A:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID	Participants received GSK2982772 oral capsule at a dose of 240 mg TID
Measure Participants	9	9
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	0.34518 (82.34)	0.59880 (158.88)

43. Secondary Outcome

Title	C12 Following BID Dosing of GSK2982772 in Part A
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis. Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	12 hours post-dose on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population

Arm/Group Title	Part A:GSK2982772 360 mg BID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 360 mg BID
Measure Participants	9
Geometric Mean (Geometric Coefficient of Variation) [Microgram per millilter]	0.3490 (98.83)

44. Secondary Outcome

Title	C24 Following BID Dosing of GSK2982772 in Part A
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	24 hours post-dose on Day 1

Outcome Measure Data

Analysis Population Description
Pharmacokinetic population

Arm/Group Title	Part A:GSK2982772 360 mg BID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 360 mg BID
Measure Participants	9
Geometric Mean (Geometric Coefficient of Variation) [Microgram per millililter]	0.36965 (101.70)

45. Secondary Outcome

Title	C0 Following TID Dosing of GSK2982772 in Part B
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose on Day 14

Outcome Measure Data

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

Arm/Group Title	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.
Measure Participants	10	8
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	0.29926 (56.63)	0.57528 (136.34)

46. Secondary Outcome

Title	C7 Following TID Dosing of GSK2982772 in Part B
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	7 hours post-dose on Days 1 and 14

Outcome Measure Data

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

Arm/Group Title	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.
Measure Participants	20	13
C7, Day 1, n=20, 13	0.3345 (50.78)	0.6105 (57.01)
C7, Day 14, n=10, 9	0.3718 (43.85)	0.6885 (75.98)

47. Secondary Outcome

Title	C14 Following TID Dosing of GSK2982772 in Part B
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	14 hours post-dose on Day 14

Outcome Measure Data

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

Arm/Group Title	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.
Measure Participants	10	9
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	0.3830 (53.04)	0.6912 (106.01)

48. Secondary Outcome

Title	C24 Following TID Dosing of GSK2982772 in Part B
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	24 hours post-dose on Day 14

Outcome Measure Data

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

Arm/Group Title	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.
Measure Participants	10	9
Geometric Mean (Geometric Coefficient of Variation) [Microgram per milliliter]	0.22712 (60.78)	0.33342 (180.82)

49. Secondary Outcome

Title	AUC([0-7] Following TID Dosing of GSK2982772 in Fed State of Part B
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 9 and 11

Outcome Measure Data

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

Arm/Group Title	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.
Measure Participants	14	9
AUC (0-7) following normal breakfast, Day 9	7.743 (31.46)	14.691 (37.63)
AUC (0-7) following high fat breakfast, Day 11	6.874 (24.64)	15.987 (42.86)

50. Secondary Outcome

Title	Cmax (0-7) Following TID Dosing of GSK2982772 in Fed State of Part B
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 9 and 11

Outcome Measure Data

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

Arm/Group Title	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.
Measure Participants	14	9
Cmax(0-7), following Normal Breakfast, Day 9	2.0918 (21.74)	3.9440 (33.82)
Cmax(0-7), following High Fat Breakfast, Day 11	1.8098 (29.77)	4.1171 (58.36)

51. Secondary Outcome

Title	Tmax (0-7) Following TID Dosing of GSK2982772 in Fed State of Part B
Description	Blood samples were collected at indicated time-points for pharmacokinetic analysis of GSK2982772.Pharmacokinetic parameters were calculated by standard non-compartmental analysis.
Time Frame	Pre-dose, 20 and 40 minutes, 1 and 1 hour 30 minutes, 2, 3, 5, 7 hours on Days 9 and 11

Outcome Measure Data

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

Arm/Group Title	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID
Arm/Group Description	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.
Measure Participants	14	9
Tmax(0-7), Day 9	3.000	3.000
Tmax (0-7), Day 11	4.000	3.000

52. Secondary Outcome

Title	Ratio of Plasma 4 Beta-hydroxycholesterol to Cholesterol: Part B
Description	Blood samples were collected into EDTA tubes and processed to plasma for 4 beta-hydroxycholesterol and cholesterol. Ratio of 4 beta-hydroxycholesterol to cholesterol is presented
Time Frame	Pre-dose on Day 1 and 24 hours post first dose on Day 14

Outcome Measure Data

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

Arm/Group Title	Part B:Placebo	Part B:GSK2982772 120 mg TID	Part B:GSK2982772 240 mg TID
Arm/Group Description	Participants received matching oral placebo capsule to GSK2928772 for 14 days	Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days	Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days.
Measure Participants	1	20	13
Day 1, Pre-dose; n=0, 19, 12	0.000019 (0.0000064)	0.000023 (0.0000099)
Day 14, 24 hour; n=1, 10, 9	0.000016 (NA)	0.000021 (0.0000089)	0.000024 (0.0000065)

Adverse Events

	Part A: Placebo		Part A:GSK2982772 120 mg TID		Part A: GSK2982772 240 mg TID		Part A: GSK2982772 360 mg BID		Part B:Placebo		Part B: GSK2982772 120 mg TID		Part B: GSK2982772 240 mg TID		Part B: GSK2982772 360 mg BID
Time Frame	On-treatment SAEs and non serious AEs were collected from the start of study treatment up to Day 14 for Part A and up to Day 28 for Part B.
Adverse Event Reporting Description	Safety population consists of all randomized participants who take at least 1 dose of study treatment.

Arm/Group Title	Part A: Placebo		Part A:GSK2982772 120 mg TID		Part A: GSK2982772 240 mg TID		Part A: GSK2982772 360 mg BID		Part B:Placebo		Part B: GSK2982772 120 mg TID		Part B: GSK2982772 240 mg TID		Part B: GSK2982772 360 mg BID
Arm/Group Description	Participants received matching oral placebo capsule to GSK2928772		Participants received GSK2982772 oral capsule at a dose of 120 mg TID		Participants received GSK2982772 oral capsule at a dose of 240 mg TID		Participants received GSK2982772 oral capsule at a dose of 360 mg BID		Participants received matching oral placebo capsule to GSK2928772 for 14 days.		Participants received GSK2982772 oral capsule at a dose of 120 mg TID for 14 days		Participants received GSK2982772 oral capsule at a dose of 240 mg TID for 14 days		Participants were planned to receive GSK2982772 oral capsule at a dose of 360 mg TID for 14 days
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	0/9 (0%)		0/9 (0%)		0/9 (0%)		0/9 (0%)		0/14 (0%)		0/20 (0%)		0/13 (0%)		0/0 (NaN)
Serious Adverse Events
	Part A: Placebo		Part A:GSK2982772 120 mg TID		Part A: GSK2982772 240 mg TID		Part A: GSK2982772 360 mg BID		Part B:Placebo		Part B: GSK2982772 120 mg TID		Part B: GSK2982772 240 mg TID		Part B: GSK2982772 360 mg BID
	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	0/9 (0%)		0/9 (0%)		0/9 (0%)		0/9 (0%)		1/14 (7.1%)		0/20 (0%)		0/13 (0%)		0/0 (NaN)
Nervous system disorders
Cerebrovascular accident	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Other (Not Including Serious) Adverse Events
	Part A: Placebo		Part A:GSK2982772 120 mg TID		Part A: GSK2982772 240 mg TID		Part A: GSK2982772 360 mg BID		Part B:Placebo		Part B: GSK2982772 120 mg TID		Part B: GSK2982772 240 mg TID		Part B: GSK2982772 360 mg BID
	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	3/9 (33.3%)		6/9 (66.7%)		4/9 (44.4%)		7/9 (77.8%)		9/14 (64.3%)		17/20 (85%)		12/13 (92.3%)		0/0 (NaN)
Cardiac disorders
Ventricular tachycardia	0/9 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	2/9 (22.2%)	2	0/14 (0%)	0	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Supraventricular tachycardia	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/14 (0%)	0	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Atrial tachycardia	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	2/14 (14.3%)	2	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Tachycardia	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	1/13 (7.7%)	1	0/0 (NaN)	0
Ear and labyrinth disorders
Ear disorder	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	1/20 (5%)	1	0/13 (0%)	0	0/0 (NaN)	0
Eye disorders
Ocular hyperaemia	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	1/13 (7.7%)	1	0/0 (NaN)	0
Gastrointestinal disorders
Abdominal pain	0/9 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Dyspepsia	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/14 (0%)	0	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Faeces soft	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Haematochezia	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Nausea	0/9 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	2/20 (10%)	2	1/13 (7.7%)	1	0/0 (NaN)	0
Toothache	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/14 (0%)	0	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Flatulence	1/9 (11.1%)	1	0/9 (0%)	0	2/9 (22.2%)	2	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Constipation	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	2/20 (10%)	2	0/13 (0%)	0	0/0 (NaN)	0
Diarrhoea	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	1/13 (7.7%)	1	0/0 (NaN)	0
Dry mouth	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	1/20 (5%)	1	0/13 (0%)	0	0/0 (NaN)	0
Hypoaesthesia oral	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	1/13 (7.7%)	1	0/0 (NaN)	0
General disorders
Medical device site dermatitis	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	1/14 (7.1%)	1	0/20 (0%)	0	1/13 (7.7%)	1	0/0 (NaN)	0
Influenza like illness	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/14 (0%)	0	0/20 (0%)	0	1/13 (7.7%)	1	0/0 (NaN)	0
Thirst	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/14 (0%)	0	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Catheter site bruise	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	3/20 (15%)	3	0/13 (0%)	0	0/0 (NaN)	0
Fatigue	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	3/20 (15%)	3	0/13 (0%)	0	0/0 (NaN)	0
Catheter site pain	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Catheter site swelling	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	1/13 (7.7%)	1	0/0 (NaN)	0
Feeling hot	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Vessel puncture site pain	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	1/13 (7.7%)	1	0/0 (NaN)	0
Immune system disorders
Seasonal allergy	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Infections and infestations
Escherichia urinary tract infection	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Nasopharyngitis	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	2/14 (14.3%)	2	1/20 (5%)	1	0/13 (0%)	0	0/0 (NaN)	0
Hordeolum	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	1/20 (5%)	1	0/13 (0%)	0	0/0 (NaN)	0
Oral herpes	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Upper respiratory tract infection	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	1/20 (5%)	1	0/13 (0%)	0	0/0 (NaN)	0
Injury, poisoning and procedural complications
Post procedural complication	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	1/20 (5%)	1	0/13 (0%)	0	0/0 (NaN)	0
Investigations
Blood creatinine increased	0/9 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Alanine aminotransferase increased	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	1/20 (5%)	1	0/13 (0%)	0	0/0 (NaN)	0
Antinuclear antibody positive	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Aspartate aminotransferase increased	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Haemoglobin decreased	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	1/13 (7.7%)	1	0/0 (NaN)	0
Musculoskeletal and connective tissue disorders
Back pain	0/9 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Muscle spasms	0/9 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Pain in extremity	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/14 (0%)	0	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Musculoskeletal pain	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	1/13 (7.7%)	1	0/0 (NaN)	0
Myalgia	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	1/20 (5%)	1	0/13 (0%)	0	0/0 (NaN)	0
Nervous system disorders
Headache	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	2/14 (14.3%)	2	3/20 (15%)	3	2/13 (15.4%)	2	0/0 (NaN)	0
Dizziness	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/14 (7.1%)	1	1/20 (5%)	1	2/13 (15.4%)	2	0/0 (NaN)	0
Lethargy	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	2/20 (10%)	2	0/13 (0%)	0	0/0 (NaN)	0
Somnolence	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	1/20 (5%)	1	0/13 (0%)	0	0/0 (NaN)	0
Tremor	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	1/20 (5%)	1	0/13 (0%)	0	0/0 (NaN)	0
Psychiatric disorders
Abnormal dreams	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	2/9 (22.2%)	2	0/14 (0%)	0	4/20 (20%)	4	1/13 (7.7%)	1	0/0 (NaN)	0
Anxiety	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	1/13 (7.7%)	1	0/0 (NaN)	0
Mood altered	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	1/13 (7.7%)	1	0/0 (NaN)	0
Nightmare	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	1/13 (7.7%)	1	0/0 (NaN)	0
Renal and urinary disorders
Polyuria	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	1/13 (7.7%)	1	0/0 (NaN)	0
Pollakiuria	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	1/13 (7.7%)	1	0/0 (NaN)	0
Reproductive system and breast disorders
Metrorrhagia	0/9 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Respiratory, thoracic and mediastinal disorders
Productive cough	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/14 (0%)	0	1/20 (5%)	1	1/13 (7.7%)	1	0/0 (NaN)	0
Sneezing	0/9 (0%)	0	0/9 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Nasal obstruction	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/14 (7.1%)	1	2/20 (10%)	2	0/13 (0%)	0	0/0 (NaN)	0
Nasal congestion	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/14 (7.1%)	1	1/20 (5%)	1	0/13 (0%)	0	0/0 (NaN)	0
Dry throat	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	1/14 (7.1%)	1	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Oropharyngeal pain	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	1/20 (5%)	1	0/13 (0%)	0	0/0 (NaN)	0
Throat irritation	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	1/13 (7.7%)	1	0/0 (NaN)	0
Skin and subcutaneous tissue disorders
Dermatitis contact	1/9 (11.1%)	1	2/9 (22.2%)	2	3/9 (33.3%)	3	3/9 (33.3%)	3	3/14 (21.4%)	4	4/20 (20%)	4	1/13 (7.7%)	1	0/0 (NaN)	0
Rash	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	1/13 (7.7%)	1	0/0 (NaN)	0
Vascular disorders
Hypertension	0/9 (0%)	0	1/9 (11.1%)	1	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	0/13 (0%)	0	0/0 (NaN)	0
Hot flush	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	1/13 (7.7%)	1	0/0 (NaN)	0
Thrombophlebitis superficial	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/9 (0%)	0	0/14 (0%)	0	0/20 (0%)	0	1/13 (7.7%)	1	0/0 (NaN)	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:

NCT03305419

Other Study ID Numbers:

205184
2017-002662-45

First Posted:

Oct 10, 2017

Last Update Posted:

Nov 1, 2019

Last Verified:

Oct 1, 2019

A Safety and Pharmacokinetic (PK) Study of GSK2982772 in Healthy Subjects

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

PART B Specific exclusion criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Outcome Measure Data

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Adverse Events

All Cause Mortality

Serious Adverse Events