Last updated: 07/17/2024 17:25:25

A safety and pharmacokinetic (PK) study of GSK2982772 in healthy subjects

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GSK study ID
205184
See study documents
Clinicaltrials.gov ID
NCT03305419
See results summary
EudraCT ID
2017-002662-45
EU CT Number
Not applicable
Trial status
Completed
Completed
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Sequential Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

Number of subjects with adverse events (AEs), serious AEs (SAEs): Part A

Timeframe: Up to Week 9

Number of subjects with AEs, SAEs: Part B

Timeframe: Up to Week 4

Number of subjects having abnormal clinical chemistry laboratory parameters as a measure of safety: Part A

Timeframe: Up to Week 9

Number of subjects having abnormal clinical chemistry laboratory parameters as a measure of safety: Part B

Timeframe: Up to Week 4

Number of subjects having abnormal hematology laboratory parameters as a measure of safety: Part A

Timeframe: Up to Week 9

Number of subjects having abnormal hematology laboratory parameters as a measure of safety: Part B

Timeframe: Up to Week 4

Number of subjects having abnormal values for urinalysis as a measure of safety: Part A

Timeframe: Up to Week 9

Number of subjects having abnormal values for urinalysis as a measure of safety: Part A

Timeframe: Up to Week 4

Number of subjects with abnormal values for blood pressure: Part A

Timeframe: Up to Week 9

Number of subjects with abnormal values for blood pressure: Part B

Timeframe: Up to Week 4

Number of subjects with abnormal values for heart rate: Part A

Timeframe: Up to Week 9

Number of subjects with abnormal values for heart rate: Part B

Timeframe: Up to Week 4

Number of subjects with abnormal respiratory rate: Part A

Timeframe: Up to Week 9

Number of subjects with abnormal respiratory rate: Part B

Timeframe: Up to Week 4

Number of subjects with abnormal values for body temperature: Part A

Timeframe: Up to Week 9

Number of subjects with abnormal values for body temperature: Part B

Timeframe: Up to Week 4

Summary of physical examinations after repeat dose administration of GSK2982772: Part A

Timeframe: Up to Day 4 in each period

Summary of physical examinations after repeat dose administration of GSK2982772: Part B

Timeframe: Up to Week 4

Number of subjects with abnormal electrocardiogram (ECG) findings: Part A

Timeframe: Up to Day 4 in each period

Number of subjects with abnormal ECG findings: Part B

Timeframe: Up to Week 4

Secondary outcomes:

Area under the concentration-time curve (AUC) from time zero to 24 hours post first dose (AUC[0-24]) following three times a day (TID) dosing of GSK2982772 120 milligrams (mg) in cohort 1: Part A

Timeframe: Pre-dose, 20,40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16, 17, 19, 22, 24hours Post-first dose

AUC(0-24) following TID dosing of GSK2982772 240 mg in cohort 1: Part A

Timeframe: Pre-dose, 20,40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16, 17, 19, 22, 24hours Post-first dose

AUC(0-24) following twice a day (BID) dosing of GSK2982772 360 mg in cohort 1: Part A

Timeframe: Pre-dose, 20,40minutes, 1hour, 1hour 30minutes, 2 , 3, 4, 6, 8, 10, 12hours, 12 hour 20minutes, 12hour 40minutes, 13hours, 13hours 30minutes, 14, 15, 16, 19, 22, 24hours Post first- dose

AUC(0-24) following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B

Timeframe: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 7,9 and 11 hours

AUC(0-24) following TID dosing of GSK2982772 120 mg on Day 9 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 9

AUC(0-24) following TID dosing of GSK2982772 120 mg on Day 11 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 11

AUC(0-24) following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B

Timeframe: Pre-dose,20,40minutes, 1hour,1hour 30minutes, 2, 3, 5, 7hours,7hours 20minutes, 7hours 40 minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16,17, 19, 22,24hours Post first-dose-Day14

AUC(0-24) following TID dosing of GSK2982772 120 mg on Day 1 in cohort 3: Part B

Timeframe: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 7,9 and 11 hours

AUC(0-24) following TID dosing of GSK2982772 120 mg on Day 9 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 9

AUC(0-24) following TID dosing of GSK2982772 120 mg on Day 11 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 11

AUC(0-24) following TID dosing of GSK2982772 120 mg on Day 14 in cohort 3: Part B

Timeframe: Pre-dose,20, 40minutes, 1hour,1hour 30minutes, 2, 3, 5, 7hours,7hours 20minutes, 7hours 40 minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16,17,19, 22,24hours Post first-dose-Day14

AUC(0-24) following BID dosing of GSK2982772 360 mg on Day 1 in cohort 5: Part B

Timeframe: Pre-dose and 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7, 9, 11 hours Post first-dose - Day 1

AUC(0-24) following BID dosing of GSK2982772 360 mg on Day 14 in cohort 5: Part B

Timeframe: Pre-dose on Day 1, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 4, 6, 8, 10, 12 hours, 12hours 20minutes, 12hours 40minutes, 13hours, 13hours 30minutes, 14, 15, 16, 19, 22, 24 hours Post first-dose -Day 14

AUC from time zero to 7 hours post first dose (AUC[0-7]) following TID dosing of GSK2982772 120 mg in cohort 1: Part A

Timeframe: Pre-dose, 20,40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16, 17, 19, 22, 24hours Post-first dose

AUC(0-7) following TID dosing of GSK2982772 240 mg in cohort 1: Part A

Timeframe: Pre-dose, 20,40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16, 17, 19, 22, 24hours Post-first dose

AUC(0-7) following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7, 9 and 11hours

AUC(0-7) following TID dosing of GSK2982772 120 mg on Day 9 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 9

AUC(0-7) following TID dosing of GSK2982772 120 mg on Day 11 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 11

AUC(0-7) following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B

Timeframe: Pre-dose,20,40minutes, 1hour,1hour 30minutes, 2, 3, 5, 7hours,7hours 20minutes, 7hours 40 minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16,17,19, 22, 24hours Post first-dose-Day14

AUC(0-7) following TID dosing of GSK2982772 120 mg on Day 1 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7, 9 and 11hours

AUC(0-7) following TID dosing of GSK2982772 120 mg on Day 9 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 9

AUC(0-7) following TID dosing of GSK2982772 120 mg on Day 11 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 11

AUC(0-7) following TID dosing of GSK2982772 120 mg on Day 14 in cohort 3: Part B

Timeframe: Pre-dose,20, 0minutes, 1hour,1hour 30minutes, 2, 3, 5, 7hours,7hours 20minutes, 7hours 40 minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16,17, 19, 22,24hours Post first-dose-Day14

AUC from 7 to 14 hours post first dose (AUC[7-14]) following TID dosing of GSK2982772 120 mg in cohort 1: Part A

Timeframe: Pre-dose,20,40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16, 17, 19, 22, 24hours Post-first dose

AUC(7-14) following TID dosing of GSK2982772 240 mg in cohort 1: Part A

Timeframe: Pre-dose, 20,40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16, 17, 19, 22, 24hours Post-first dose

AUC(7-14) following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7, 9 and 11hours

AUC(7-14) following TID dosing of GSK2982772 120 mg on Day 9 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 9

AUC(7-14) following TID dosing of GSK2982772 120 mg on Day 11 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 11

AUC(7-14) following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B

Timeframe: Pre-dose,20,40minutes, 1hour,1hour 30minutes, 2, 3, 5, 7hours,7hours 20minutes, 7hours 40 minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16,17, 19, 22,24hours Post first-dose-Day14

AUC(7-14) following TID dosing of GSK2982772 120 mg on Day 1 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7, 9 and 11hours

AUC(7-14) following TID dosing of GSK2982772 120 mg on Day 9 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 9

AUC(7-14) following TID dosing of GSK2982772 120 mg on Day 11 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 11

AUC(7-14) following TID dosing of GSK2982772 120 mg on Day 14 in cohort 3: Part B

Timeframe: Pre-dose,20,40minutes, 1hour,1hour 30minutes, 2, 3, 5, 7hours,7hours 20minutes, 7hours 40 minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16,17, 19, 22,24hours Post first-dose-Day14

AUC from 14 to 24 hours post first dose (AUC[14-24]) following TID dosing of GSK2982772 120 mg in cohort 1: Part A

Timeframe: Pre-dose, 20,40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16, 17, 19, 22, 24hours Post-first dose

AUC(14-24) following TID dosing of GSK2982772 240 mg in cohort 1: Part A

Timeframe: Pre-dose, 20,40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16, 17, 19, 22, 24hours Post-first dose

AUC(14-24) following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7,9 and 11 hours

AUC(14-24) following TID dosing of GSK2982772 120 mg on Day 9 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 9

AUC(14-24) following TID dosing of GSK2982772 120 mg on Day 11 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 11

AUC(14-24) following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B

Timeframe: Pre-dose,20,40minutes, 1hour,1hour 30minutes, 2, 3, 5, 7hours,7hours 20minutes, 7hours 40 minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16,17, 19, 22,24hours Post first-dose-Day14

AUC(14-24) following TID dosing of GSK2982772 120 mg on Day 1 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7,9 and 11 hours

AUC(14-24) following TID dosing of GSK2982772 120 mg on Day 9 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 9

AUC(14-24) following TID dosing of GSK2982772 120 mg on Day 11 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 11

AUC(14-24) following TID dosing of GSK2982772 120 mg on Day 14 in cohort 3: Part B

Timeframe: Pre-dose,20,40minutes, 1hour,1hour 30minutes, 2, 3, 5, 7hours,7hours 20minutes, 7hours 40 minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16,17, 19, 22,24hours Post first-dose-Day14

AUC from 0 to 12 hours post first dose (AUC[0-12] following BID dosing of GSK2982772 360 mg in cohort 1: Part A

Timeframe: Pre-dose, 20,40minutes, 1hour, 1hour 30minutes, 2 , 3, 4, 6, 8, 10, 12hours, 12 hour 20minutes, 12hour 40minutes, 13hours, 13hours 30minutes, 14, 15, 16, 19, 22, 24hours Post first- dose

AUC(0-12) following BID dosing of GSK2982772 360 mg on Day 1 in cohort 5: Part B

Timeframe: Pre-dose and 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7, 9, 11 hours Post first-dose - Day 1

AUC(0-12) following BID dosing of GSK2982772 360 mg on Day 14 in cohort 5: Part B

Timeframe: Pre-dose on Day 1, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 4, 6, 8, 10, 12 hours, 12hours 20minutes, 12hours 40minutes, 13hours, 13hours 30minutes, 14, 15, 16, 19, 22, 24 hours Post first-dose -Day 14

AUC from 12 to 24 hours post first dose (AUC[12-24]) for BID dosing of GSK2982772 360 mg in cohort 1: Part A

Timeframe: Pre-dose, 20,40minutes, 1hour, 1hour 30minutes, 2 , 3, 4, 6, 8, 10, 12hours, 12 hour 20minutes, 12hour 40minutes, 13hours, 13hours 30minutes, 14, 15, 16, 19, 22, 24hours Post first- dose

AUC(12-24) following BID dosing of GSK2982772 360 mg on Day 1 in cohort 5: Part B

Timeframe: Pre-dose and 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7, 9, 11 hours Post first-dose - Day 1

AUC(12-24) following BID dosing of GSK2982772 360 mg on Day 14 in cohort 5: Part B

Timeframe: Pre-dose on Day 1, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 4, 6, 8, 10, 12 hours, 12hours 20minutes, 12hours 40minutes, 13hours, 13hours 30minutes, 14, 15, 16, 19, 22, 24 hours Post first-dose -Day 14

Maximum observed plasma drug concentration (Cmax) following TID dosing of GSK2982772 120 mg in cohort 1: Part A

Timeframe: Pre-dose, 20,40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16, 17, 19, 22, 24hours Post-first dose

Cmax following TID dosing of GSK2982772 240 mg in cohort 1: Part A

Timeframe: Pre-dose, 20,40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16, 19, 22, 24hours Post-first dose

Cmax following BID dosing of GSK2982772 360 mg in cohort 1: Part A

Timeframe: Pre-dose, 20,40minutes, 1hour, 1hour 30minutes, 2 , 3, 4, 6, 8, 10, 12hours, 12 hour 20minutes, 12hour 40minutes, 13hours, 13hours 30minutes, 14, 15, 16, 17, 19, 22, 24hours Post first- dose

Cmax following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7,9 and 11 hours

Cmax following TID dosing of GSK2982772 120 mg on Day 9 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 9

Cmax following TID dosing of GSK2982772 120 mg on Day 11 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 11

Cmax following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B

Timeframe: Pre-dose,20,40minutes, 1hour,1hour 30minutes, 2, 3, 5, 7hours,7hours 20minutes, 7hours 40 minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16,17, 19, 22,24hours Post first-dose-Day14

Cmax following TID dosing of GSK2982772 120 mg on Day 1 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7,9 and 11 hours

Cmax following TID dosing of GSK2982772 120 mg on Day 9 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 9

Cmax following TID dosing of GSK2982772 120 mg on Day 11 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 11

Cmax following TID dosing of GSK2982772 120 mg on Day 14 in cohort 3: Part B

Timeframe: Pre-dose, 20,40minutes, 1hour,1hour 30minutes, 2, 3, 5, 7hours,7hours 20minutes, 7hours 40 minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16,17,19,22, 24hours Post first-dose-Day14

Cmax following BID dosing of GSK2982772 360 mg on Day 1 in cohort 5: Part B

Timeframe: Pre-dose and 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7, 9, 11 hours Post first-dose - Day 1

Cmax following BID dosing of GSK2982772 360 mg on Day 14 in cohort 5: Part B

Timeframe: Pre-dose on Day 1, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 4, 6, 8, 10, 12 hours, 12hours 20minutes, 12hours 40minutes, 13hours, 13hours 30minutes, 14, 15, 16, 19, 22, 24 hours Post first-dose -Day 14

Time to Cmax (Tmax) following TID dosing of GSK2982772 120 mg in cohort 1: Part A

Timeframe: Pre-dose, 20,40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16, 17. 19, 22, 24hours Post-first dose

Tmax following TID dosing of GSK2982772 240 mg in cohort 1: Part A

Timeframe: Pre-dose, 20,40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16, 17, 19, 22, 24hours Post-first dose

Tmax following BID dosing of GSK2982772 360 mg in cohort 1: Part A

Timeframe: Pre-dose, 20,40minutes, 1hour, 1hour 30minutes, 2 , 3, 4, 6, 8, 10, 12hours, 12 hour 20minutes, 12hour 40minutes, 13hours, 13hours 30minutes, 14, 15, 16, 19, 22, 24hours Post first- dose

Tmax following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7,9 and 11 hours

Tmax following TID dosing of GSK2982772 120 mg on Day 9 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 9

Tmax following TID dosing of GSK2982772 120 mg on Day 11 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 11

Tmax following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B

Timeframe: Pre-dose,20,40minutes, 1hour,1hour 30minutes, 2, 3, 5, 7hours,7hours 20minutes, 7hours 40 minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16,17, 19, 22,24hours Post first-dose-Day14

Tmax following TID dosing of GSK2982772 120 mg on Day 1 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7,9 and 11 hours

Tmax following TID dosing of GSK2982772 120 mg on Day 9 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 9

Tmax following TID dosing of GSK2982772 120 mg on Day 11 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 11

Tmax following TID dosing of GSK2982772 120 mg on Day 14 in cohort 3: Part B

Timeframe: Pre-dose,20,40minutes, 1hour,1hour 30minutes, 2, 3, 5, 7hours,7hours 20minutes, 7hours 40 minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16,17, 19, 22,24hours Post first-dose-Day14

Tmax following BID dosing of GSK2982772 360 mg on Day 1 in cohort 5: Part B

Timeframe: Pre-dose and 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7, 9, 11 hours Post first-dose - Day 1

Tmax following BID dosing of GSK2982772 360 mg on Day 14 in cohort 5: Part B

Timeframe: Pre-dose on Day 1, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 4, 6, 8, 10, 12 hours, 12hours 20minutes, 12hours 40minutes, 13hours, 13hours 30minutes, 14, 15, 16, 19, 22, 24 hours Post first-dose -Day 14

Observed trough plasma drug concentration at 0 hour (C0) following TID dosing of GSK2982772 120 mg in cohort 1 : Part A

Timeframe: Pre first-dose

C0 following TID dosing of GSK2982772 240 mg in cohort 1: Part A

Timeframe: Pre first-dose

C0 following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7,9 and 11 hours

C0 following TID dosing of GSK2982772 120 mg on Day 9 in cohort 2: Part B

Timeframe: Pre first-dose -Day9

C0 following TID dosing of GSK2982772 120 mg on Day 11 in cohort 2: Part B

Timeframe: Pre first-dose -Day11

C0 following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B

Timeframe: Pre first dose -Day14

C0 following TID dosing of GSK2982772 120 mg on Day 1 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7,9 and 11 hours

C0 following TID dosing of GSK2982772 120 mg on Day 9 in cohort 3: Part B

Timeframe: Pre first dose -Day9

C0 following TID dosing of GSK2982772 120 mg on Day 11 in cohort 3: Part B

Timeframe: Pre first dose -Day11

C0 following TID dosing of GSK2982772 120 mg on Day 14 in cohort 3: Part B

Timeframe: Pre first dose -Day14

Observed trough plasma drug concentration at 7 hours (C7) following TID dosing of GSK2982772 120 mg in cohort 1 : Part A

Timeframe: Pre-dose, 7 hours post first dose (prior to second dose)

C7 following TID dosing of GSK2982772 240 mg in cohort 1: Part A

Timeframe: Pre-dose, 7 hours post first dose (prior to second dose)

C7 following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7,9 and 11 hours

C7 following TID dosing of GSK2982772 120 mg on Day 9 in cohort 2: Part B

Timeframe: Pre-dose, 7 hours post first dose (prior to second dose) -Day9

C7 following TID dosing of GSK2982772 120 mg on Day 11 in cohort 2: Part B

Timeframe: Pre-dose, 7 hours post first dose (prior to second dose)-Day11

C7 following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B

Timeframe: 7 hours post first dose (prior to second dose) -Day14

C7 following TID dosing of GSK2982772 120 mg on Day 1 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7,9 and 11 hours

C7 following TID dosing of GSK2982772 120 mg on Day 9 in cohort 3: Part B

Timeframe: Pre-dose, 7 hours post first dose (prior to second dose) -Day9

C7 following TID dosing of GSK2982772 120 mg on Day 11 in cohort 3: Part B

Timeframe: Pre-dose, 7 hours post first dose (prior to second dose) -Day11

C7 following TID dosing of GSK2982772 120 mg on Day 14 in cohort 3: Part B

Timeframe: 7 hours post first dose (prior to second dose) -Day14

Observed trough plasma drug concentration at 14 hours (C14) following TID dosing of GSK2982772 120 mg in cohort 1 : Part A

Timeframe: 14 hours post first dose (prior to third dose)

C14 following TID dosing of GSK2982772 240 mg in cohort 1: Part A

Timeframe: 14 hours post first dose (prior to third dose)

C14 following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7,9 and 11 hours

C14 following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B

Timeframe: 14 hours post first dose (prior to third dose) -Day14

C14 following TID dosing of GSK2982772 120 mg on Day 1 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7,9 and 11 hours

C14 following TID dosing of GSK2982772 120 mg on Day 14 in cohort 3: Part B

Timeframe: 14 hours post first dose (prior to third dose) -Day14

Observed trough plasma drug concentration at 24 hours (C24) following TID dosing of GSK2982772 120 mg in cohort 1 : Part A

Timeframe: 24 hours post first dose

C24 following TID dosing of GSK2982772 240 mg in cohort 1: Part A

Timeframe: 24 hours post first dose

C24 following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7,9 and 11 hours

C24 following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B

Timeframe: 24 hours post first dose -Day14

C24 following TID dosing of GSK2982772 120 mg on Day 1 in cohort 3: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7,9 and 11 hours

C24 following TID dosing of GSK2982772 120 mg on Day 14 in cohort 3: Part B

Timeframe: 24 hours post first dose -Day14

C0 following BID dosing of GSK2982772 360 mg in cohort 1 : Part A

Timeframe: Pre first dose

C0 following BID dosing of GSK2982772 360 mg on Day 1 in cohort 5: Part B

Timeframe: Pre first dose -Day1

C0 following BID dosing of GSK2982772 360 mg on Day 14 in cohort 5: Part B

Timeframe: Pre first dose -Day14

C12 following BID dosing of GSK2982772 360 mg in cohort 1 : Part A

Timeframe: 12 hours post first dose (prior to second dose)

C12 following BID dosing of GSK2982772 360 mg on Day 1 in cohort 5: Part B

Timeframe: 12 hours post first dose (prior to second dose) -Day1

C12 following BID dosing of GSK2982772 360 mg on Day 14 in cohort 5: Part B

Timeframe: 12 hours post first dose (prior to second dose) -Day14

C24 following BID dosing of GSK2982772 360 mg in cohort 1 : Part A

Timeframe: 24 hours post first dose

C24 following BID dosing of GSK2982772 360 mg on Day 1 in cohort 5: Part B

Timeframe: 24 hours post first dose -Day1

C24 following BID dosing of GSK2982772 360 mg on Day 14 in cohort 5: Part B

Timeframe: 24 hours post first dose -Day14

Ratio of plasma 4beta-hydroxycholesterol to cholesterol during pre-treatment and following repeat dosing of GSK2982772: Part B

Timeframe: Pre-dose on Day 1 and, 24 hours Post first -dose-Day 14

AUC(0-24) following TID dosing of GSK2982772 240 mg on Day 1 in Cohort 4: Part B

Timeframe: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7,9 and 11hours

AUC(0-24) following TID dosing of GSK2982772 240 mg on Day 9 in Cohort 4: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 9

AUC(0-24) following TID dosing of GSK2982772 240 mg on Day 11 in Cohort 4: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 11

AUC(0-24) following TID dosing of GSK2982772 240 mg on Day 14 in Cohort 4: Part B

Timeframe: Pre-dose,20, 40minutes, 1hour,1hour 30minutes, 2, 3, 5, 7hours,7hours 20minutes, 7hours 40 minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16,17,19, 22,24hours Post first-dose-Day14

AUC(0-7) following TID dosing of GSK2982772 240 mg on Day 1 in Cohort 4: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7,9 and 11 hours

AUC(0-7) following TID dosing of GSK2982772 240 mg on Day 9 in Cohort 4: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 9

AUC(0-7) following TID dosing of GSK2982772 240 mg on Day 11 in Cohort 4: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 11

AUC(0-7) following TID dosing of GSK2982772 240 mg on Day 14 in Cohort 4: Part B

Timeframe: Pre-dose,20, 0minutes, 1hour,1hour 30minutes, 2, 3, 5, 7hours,7hours 20minutes, 7hours 40 minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16,17, 19, 22,24hours Post first-dose-Day14

AUC(7-14) following TID dosing of GSK2982772 240 mg on Day 1 in Cohort 4: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7,9 and 11 hours

AUC(7-14) following TID dosing of GSK2982772 240 mg on Day 9 in Cohort 4: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 9

AUC(7-14) following TID dosing of GSK2982772 240 mg on Day 11 in Cohort 4: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 11

AUC(7-14) following TID dosing of GSK2982772 240 mg on Day 14 in Cohort 4: Part B

Timeframe: Pre-dose,20,40minutes, 1hour,1hour 30minutes, 2, 3, 5, 7hours,7hours 20minutes, 7hours 40 minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16,17, 19, 22,24hours Post first-dose-Day14

AUC(14-24) following TID dosing of GSK2982772 240 mg on Day 1 in Cohort 4: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7, 9 and 11 hours

AUC(14-24) following TID dosing of GSK2982772 240 mg on Day 9 in Cohort 4: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 9

AUC(14-24) following TID dosing of GSK2982772 240 mg on Day 11 in Cohort 4: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 11

AUC(14-24) following TID dosing of GSK2982772 240 mg on Day 14 in Cohort 4: Part B

Timeframe: Pre-dose,20,40minutes, 1hour,1hour 30minutes, 2, 3, 5, 7hours,7hours 20minutes, 7hours 40 minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16,17, 19, 22,24hours Post first-dose-Day14

Cmax following TID dosing of GSK2982772 240 mg on Day 1 in Cohort 4: Part B

Timeframe: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7, 9 and 11 hours

Cmax following TID dosing of GSK2982772 240 mg on Day 9 in Cohort 4: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 9

Cmax following TID dosing of GSK2982772 240 mg on Day 11 in Cohort 4: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 11

Cmax following TID dosing of GSK2982772 240 mg on Day 14 in Cohort 4: Part B

Timeframe: Pre-dose, 20,40minutes, 1hour,1hour 30minutes, 2, 3, 5, 7hours,7hours 20minutes, 7hours 40 minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16,17,19,22, 24hours Post first-dose-Day14

Tmax following TID dosing of GSK2982772 240 mg on Day 1 in Cohort 4: Part B

Timeframe: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7, 9 and 11 hours

Tmax following TID dosing of GSK2982772 240 mg on Day 9 in Cohort 4: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 9

Tmax following TID dosing of GSK2982772 240 mg on Day 11 in Cohort 4: Part B

Timeframe: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5, 7 hours, 7hours 20minutes, 7hours 40minutes, 8hours, 8hours 30minutes, 9, 10, 12 hours Post first-dose - Day 11

Tmax following TID dosing of GSK2982772 240 mg on Day 14 in Cohort 4: Part B

Timeframe: Pre-dose,20,40minutes, 1hour,1hour 30minutes, 2, 3, 5, 7hours,7hours 20minutes, 7hours 40 minutes, 8hours, 8hours 30minutes, 9, 10, 12, 14hours, 14hours 20minutes, 14hours 40minutes, 15hours, 15hours 30minutes, 16,17, 19, 22,24hours Post first-dose-Day14

C0 following TID dosing of GSK2982772 240 mg on Day 1 in Cohort 4: Part B

Timeframe: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7, 9 and 11 hours

C0 following TID dosing of GSK2982772 240 mg on Day 9 in Cohort 4: Part B

Timeframe: Pre first dose -Day9

C0 following TID dosing of GSK2982772 240 mg on Day 11 in Cohort 4: Part B

Timeframe: Pre first dose -Day11

C0 following TID dosing of GSK2982772 240 mg on Day 14 in Cohort 4: Part B

Timeframe: Pre first dose -Day14

C7 following TID dosing of GSK2982772 240 mg on Day 1 in Cohort 4: Part B

Timeframe: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7, 9 and 11 hours

C7 following TID dosing of GSK2982772 240 mg on Day 9 in Cohort 4: Part B

Timeframe: Pre-dose, 7 hours post first dose (prior to second dose) -Day9

C7 following TID dosing of GSK2982772 240 mg on Day 11 in Cohort 4: Part B

Timeframe: Pre-dose, 7 hours post first dose (prior to second dose) -Day11

C7 following TID dosing of GSK2982772 240 mg on Day 14 in Cohort 4: Part B

Timeframe: 7 hours post first dose (prior to second dose) -Day14

C14 following TID dosing of GSK2982772 240 mg on Day 1 in Cohort 4: Part B

Timeframe: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7, 9 and 11 hours

C14 following TID dosing of GSK2982772 240 mg on Day 14 in Cohort 4: Part B

Timeframe: 14 hours post first dose (prior to third dose) -Day14

C24 following TID dosing of GSK2982772 240 mg on Day 1 in Cohort 4: Part B

Timeframe: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5,7, 9 and 11 hours

C24 following TID dosing of GSK2982772 240 mg on Day 14 in Cohort 4: Part B

Timeframe: 24 hours post first dose -Day14

Interventions:
Drug: GSK2982772 capsule
Drug: Placebo capsule
Enrollment:
62
Observational study model:
Not applicable
Primary completion date:
2018-15-10
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Autoimmune Diseases
Product
GSK2982772
Collaborators
Not applicable
Study date(s)
October 2017 to October 2018
Type
Interventional
Phase
1

Participation criteria

Sex
Female & Male
Age
18 - 65 years
Accepts healthy volunteers
Yes
  • 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.
  • 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.
Inclusion and exclusion criteria
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.

Trial location(s)

Location
Status
Contact us
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Location
GSK Investigational Site
Cambridge, United Kingdom, CB2 2GG
Status
Study Complete
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Study documents

Study report synopsis
Available language(s): English
Download document(s)
Protocol
Available language(s): English
Download document(s)
Statistical analysis plan
Available language(s): English
Download document(s)

If you wish to request for full study report, please contact - [email protected]

Results overview

Results posted on ClinicalTrials.gov

Recruitment status
Completed
Actual primary completion date
2018-15-10
Actual study completion date
2018-15-10

Plain language summaries

Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

Additional information about the trial

Additional information
Not applicable
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