ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03305419
Recruitment Status : Suspended (Dosing was suspended in Study 205184 to allow time to evaluate cases of asymptomatic arrhythmia adverse events, detected during planned telemetry monitoring.)
First Posted : October 10, 2017
Last Update Posted : March 23, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

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 and 4) - 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 and in sequential groups for 14 days in Part B. Approximately 48 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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 66 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.
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 : October 11, 2017
Estimated Primary Completion Date : October 22, 2018
Estimated Study Completion Date : October 22, 2018

Resource links provided by the National Library of Medicine


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 240 mg TID in cohort 3 : 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 4: 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.




Primary Outcome Measures :
  1. Number of subjects with adverse events (AEs), serious AEs (SAEs): Part A [ Time Frame: Up to Week 9 ]
    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.

  2. Number of subjects with AEs, SAEs: Part B [ Time Frame: Up to Week 4 ]
    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.

  3. Number of subjects having abnormal clinical chemistry laboratory parameters as a measure of safety: Part A [ Time Frame: Up to Week 9 ]
    Laboratory assessment for clinical chemistry parameters will include blood urea nitrogen (BUN), potassium, calcium, sodium, creatinine, fasting glucose, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline phosphatase, total protein, albumin, total and direct bilirubin and C-reactive protein (CRP).

  4. Number of subjects having abnormal clinical chemistry laboratory parameters as a measure of safety: Part B [ Time Frame: Up to Week 4 ]
    Laboratory assessment for clinical chemistry parameters will include BUN, potassium, calcium, sodium, creatinine, fasting glucose, AST, ALT, Alkaline phosphatase, Anti-nuclear antibody (ANA), total protein, albumin, total and direct bilirubin and CRP.

  5. Number of subjects having abnormal hematology laboratory parameters as a measure of safety: Part A [ Time Frame: Up to Week 9 ]
    Laboratory assessment for hematology parameters will include Platelet count, hemoglobin, Red blood cell (RBC) count, hematocrit, mean corpuscular volume (MCV), percentage reticulocytes, Mean corpuscular hemoglobin (MCH), white blood cell (WBC) count, neutrophils, lymphocytes, monocytes, eosinophils and basophils.

  6. Number of subjects having abnormal hematology laboratory parameters as a measure of safety: Part B [ Time Frame: Up to Week 4 ]
    Laboratory assessment for hematology parameters will include Platelet count, hemoglobin, RBC count, hematocrit, MCV, percentage reticulocytes, MCH, . WBC count, neutrophils, lymphocytes, monocytes, eosinophils and basophils.

  7. Number of subjects having abnormal values for urinalysis as a measure of safety: Part A [ Time Frame: Up to Week 9 ]
    Laboratory assessment for urinalysis will include specific gravity, potential of hydrogen (pH), glucose, protein, blood, ketones by dipstick, microscopic examination if blood or protein is abnormal.

  8. Number of subjects having abnormal values for urinalysis as a measure of safety: Part A [ Time Frame: Up to Week 4 ]
    Laboratory assessment for urinalysis will include specific gravity, pH, glucose, protein, blood, ketones by dipstick, microscopic examination if blood or protein is abnormal.

  9. Number of subjects with abnormal values for blood pressure: Part A [ Time Frame: Up to Week 9 ]
    Systolic and diastolic blood pressure will be measured in a supine position after 5 minutes of rest.

  10. Number of subjects with abnormal values for blood pressure: Part B [ Time Frame: Up to Week 4 ]
    Systolic and diastolic blood pressure will be measured in a supine position after 5 minutes of rest.

  11. Number of subjects with abnormal values for heart rate: Part A [ Time Frame: Up to Week 9 ]
    Heart rate will be measured in a supine position after 5 minutes rest.

  12. Number of subjects with abnormal values for heart rate: Part B [ Time Frame: Up to Week 4 ]
    Heart rate will be measured in a supine position after 5 minutes rest.

  13. Number of subjects with abnormal respiratory rate: Part A [ Time Frame: Up to Week 9 ]
    Respiratory rate will be measured in a supine after at least a 5-min rest.

  14. Number of subjects with abnormal respiratory rate: Part B [ Time Frame: Up to Week 4 ]
    Respiratory rate will be measured in a supine position after at least a 5-min rest.

  15. Number of subjects with abnormal values for body temperature: Part A [ Time Frame: Up to Week 9 ]
    Body temperature will be measured in a supine position after at least a 5-min rest.

  16. Number of subjects with abnormal values for body temperature: Part B [ Time Frame: Up to Week 4 ]
    Body temperature will be measured in a supine position after at least a 5-min rest.

  17. Summary of physical examinations after repeat dose administration of GSK2982772: Part A [ Time Frame: Up to Day 4 in each period ]
    A complete physical examination will include assessment of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Height and weight will also be measured and recorded. A brief physical examination will include assessments of the skin, lungs, cardiovascular system and abdomen (liver and spleen).

  18. Summary of physical examinations after repeat dose administration of GSK2982772: Part B [ Time Frame: Up to Week 4 ]
    A complete physical examination will include assessment of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Height and weight will also be measured and recorded. A brief physical examination will include assessments of the skin, lungs, cardiovascular system and abdomen (liver and spleen).

  19. Number of subjects with abnormal electrocardiogram (ECG) findings: Part A [ Time Frame: Up to Day 4 in each period ]
    A 12-lead ECGs will be obtained using ECG machine.

  20. Number of subjects with abnormal ECG findings: Part B [ Time Frame: Up to Week 4 ]
    A 12-lead ECGs will be obtained using ECG machine.


Secondary Outcome Measures :
  1. 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 [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  2. AUC(0-24) following TID dosing of GSK2982772 240 mg in cohort 1: Part A [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  3. AUC(0-24) following twice a day (BID) dosing of GSK2982772 360 mg in cohort 1: Part A [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  4. AUC(0-24) following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B [ Time Frame: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  5. AUC(0-24) following TID dosing of GSK2982772 120 mg on Day 9 in cohort 2: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  6. AUC(0-24) following TID dosing of GSK2982772 120 mg on Day 11 in cohort 2: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  7. AUC(0-24) following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  8. AUC(0-24) following TID dosing of GSK2982772 240 mg on Day 1 in cohort 3: Part B [ Time Frame: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  9. AUC(0-24) following TID dosing of GSK2982772 240 mg on Day 9 in cohort 3: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  10. AUC(0-24) following TID dosing of GSK2982772 240 mg on Day 11 in cohort 3: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  11. AUC(0-24) following TID dosing of GSK2982772 240 mg on Day 14 in cohort 3: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  12. AUC(0-24) following BID dosing of GSK2982772 360 mg on Day 1 in cohort 4: Part B [ Time Frame: Pre-dose and 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 1 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  13. AUC(0-24) following BID dosing of GSK2982772 360 mg on Day 14 in cohort 4: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  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 [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  15. AUC(0-7) following TID dosing of GSK2982772 240 mg in cohort 1: Part A [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  16. AUC(0-7) following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B [ Time Frame: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  17. AUC(0-7) following TID dosing of GSK2982772 120 mg on Day 9 in cohort 2: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  18. AUC(0-7) following TID dosing of GSK2982772 120 mg on Day 11 in cohort 2: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  19. AUC(0-7) following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  20. AUC(0-7) following TID dosing of GSK2982772 240 mg on Day 1 in cohort 3: Part B [ Time Frame: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  21. AUC(0-7) following TID dosing of GSK2982772 240 mg on Day 9 in cohort 3: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  22. AUC(0-7) following TID dosing of GSK2982772 240 mg on Day 11 in cohort 3: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  23. AUC(0-7) following TID dosing of GSK2982772 240 mg on Day 14 in cohort 3: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  24. AUC from 7 to 14 hours post first dose (AUC[7-14]) following TID dosing of GSK2982772 120 mg in cohort 1: Part A [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  25. AUC(7-14) following TID dosing of GSK2982772 240 mg in cohort 1: Part A [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  26. AUC(7-14) following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B [ Time Frame: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  27. AUC(7-14) following TID dosing of GSK2982772 120 mg on Day 9 in cohort 2: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  28. AUC(7-14) following TID dosing of GSK2982772 120 mg on Day 11 in cohort 2: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  29. AUC(7-14) following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  30. AUC(7-14) following TID dosing of GSK2982772 240 mg on Day 1 in cohort 3: Part B [ Time Frame: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  31. AUC(7-14) following TID dosing of GSK2982772 240 mg on Day 9 in cohort 3: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  32. AUC(7-14) following TID dosing of GSK2982772 240 mg on Day 11 in cohort 3: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  33. AUC(7-14) following TID dosing of GSK2982772 240 mg on Day 14 in cohort 3: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  34. AUC from 14 to 24 hours post first dose (AUC[14-24]) following TID dosing of GSK2982772 120 mg in cohort 1: Part A [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  35. AUC(14-24) following TID dosing of GSK2982772 240 mg in cohort 1: Part A [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  36. AUC(14-24) following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B [ Time Frame: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  37. AUC(14-24) following TID dosing of GSK2982772 120 mg on Day 9 in cohort 2: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  38. AUC(14-24) following TID dosing of GSK2982772 120 mg on Day 11 in cohort 2: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  39. AUC(14-24) following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  40. AUC(14-24) following TID dosing of GSK2982772 240 mg on Day 1 in cohort 3: Part B [ Time Frame: Pre-dose, 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  41. AUC(14-24) following TID dosing of GSK2982772 240 mg on Day 9 in cohort 3: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  42. AUC(14-24) following TID dosing of GSK2982772 240 mg on Day 11 in cohort 3: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  43. AUC(14-24) following TID dosing of GSK2982772 240 mg on Day 14 in cohort 3: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  44. AUC from 0 to 12 hours post first dose (AUC[0-12] following BID dosing of GSK2982772 360 mg in cohort 1: Part A [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  45. AUC(0-12) following BID dosing of GSK2982772 360 mg on Day 1 in cohort 4: Part B [ Time Frame: Pre-dose and 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 1 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  46. AUC(0-12) following BID dosing of GSK2982772 360 mg on Day 14 in cohort 4: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  47. AUC from 12 to 24 hours post first dose (AUC[12-24]) for BID dosing of GSK2982772 360 mg in cohort 1: Part A [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  48. AUC(12-24) following BID dosing of GSK2982772 360 mg on Day 1 in cohort 4: Part B [ Time Frame: Pre-dose and 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 1 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  49. AUC(12-24) following BID dosing of GSK2982772 360 mg on Day 14 in cohort 4: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  50. Maximum observed plasma drug concentration (Cmax) following TID dosing of GSK2982772 120 mg in cohort 1: Part A [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  51. Cmax following TID dosing of GSK2982772 240 mg in cohort 1: Part A [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  52. Cmax following BID dosing of GSK2982772 360 mg in cohort 1: Part A [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  53. Cmax following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B [ Time Frame: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  54. Cmax following TID dosing of GSK2982772 120 mg on Day 9 in cohort 2: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  55. Cmax following TID dosing of GSK2982772 120 mg on Day 11 in cohort 2: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  56. Cmax following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  57. Cmax following TID dosing of GSK2982772 240 mg on Day 1 in cohort 3: Part B [ Time Frame: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  58. Cmax following TID dosing of GSK2982772 240 mg on Day 9 in cohort 3: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  59. Cmax following TID dosing of GSK2982772 240 mg on Day 11 in cohort 3: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  60. Cmax following TID dosing of GSK2982772 240 mg on Day 14 in cohort 3: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  61. Cmax following BID dosing of GSK2982772 360 mg on Day 1 in cohort 4: Part B [ Time Frame: Pre-dose and 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 1 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  62. Cmax following BID dosing of GSK2982772 360 mg on Day 14 in cohort 4: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  63. Time to Cmax (Tmax) following TID dosing of GSK2982772 120 mg in cohort 1: Part A [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  64. Tmax following TID dosing of GSK2982772 240 mg in cohort 1: Part A [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  65. Tmax following BID dosing of GSK2982772 360 mg in cohort 1: Part A [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  66. Tmax following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B [ Time Frame: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  67. Tmax following TID dosing of GSK2982772 120 mg on Day 9 in cohort 2: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  68. Tmax following TID dosing of GSK2982772 120 mg on Day 11 in cohort 2: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  69. Tmax following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  70. Tmax following TID dosing of GSK2982772 240 mg on Day 1 in cohort 3: Part B [ Time Frame: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  71. Tmax following TID dosing of GSK2982772 240 mg on Day 9 in cohort 3: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  72. Tmax following TID dosing of GSK2982772 240 mg on Day 11 in cohort 3: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  73. Tmax following TID dosing of GSK2982772 240 mg on Day 14 in cohort 3: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  74. Tmax following BID dosing of GSK2982772 360 mg on Day 1 in cohort 4: Part B [ Time Frame: Pre-dose and 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 1 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  75. Tmax following BID dosing of GSK2982772 360 mg on Day 14 in cohort 4: Part B [ Time Frame: 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 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  76. Observed trough plasma drug concentration at 0 hour (C0) following TID dosing of GSK2982772 120 mg in cohort 1 : Part A [ Time Frame: Pre first-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  77. C0 following TID dosing of GSK2982772 240 mg in cohort 1: Part A [ Time Frame: Pre first-dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  78. C0 following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B [ Time Frame: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  79. C0 following TID dosing of GSK2982772 120 mg on Day 9 in cohort 2: Part B [ Time Frame: Pre first-dose -Day9 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  80. C0 following TID dosing of GSK2982772 120 mg on Day 11 in cohort 2: Part B [ Time Frame: Pre first-dose -Day11 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  81. C0 following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B [ Time Frame: Pre first dose -Day14 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  82. C0 following TID dosing of GSK2982772 240 mg on Day 1 in cohort 3: Part B [ Time Frame: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  83. C0 following TID dosing of GSK2982772 240 mg on Day 9 in cohort 3: Part B [ Time Frame: Pre first dose -Day9 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  84. C0 following TID dosing of GSK2982772 240 mg on Day 11 in cohort 3: Part B [ Time Frame: Pre first dose -Day11 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  85. C0 following TID dosing of GSK2982772 240 mg on Day 14 in cohort 3: Part B [ Time Frame: Pre first dose -Day14 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  86. Observed trough plasma drug concentration at 7 hours (C7) following TID dosing of GSK2982772 120 mg in cohort 1 : Part A [ Time Frame: Pre-dose, 7 hours post first dose (prior to second dose) ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  87. C7 following TID dosing of GSK2982772 240 mg in cohort 1: Part A [ Time Frame: Pre-dose, 7 hours post first dose (prior to second dose) ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  88. C7 following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B [ Time Frame: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  89. C7 following TID dosing of GSK2982772 120 mg on Day 9 in cohort 2: Part B [ Time Frame: Pre-dose, 7 hours post first dose (prior to second dose) -Day9 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  90. C7 following TID dosing of GSK2982772 120 mg on Day 11 in cohort 2: Part B [ Time Frame: Pre-dose, 7 hours post first dose (prior to second dose)-Day11 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  91. C7 following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B [ Time Frame: 7 hours post first dose (prior to second dose) -Day14 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  92. C7 following TID dosing of GSK2982772 240 mg on Day 1 in cohort 3: Part B [ Time Frame: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  93. C7 following TID dosing of GSK2982772 240 mg on Day 9 in cohort 3: Part B [ Time Frame: Pre-dose, 7 hours post first dose (prior to second dose) -Day9 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  94. C7 following TID dosing of GSK2982772 240 mg on Day 11 in cohort 3: Part B [ Time Frame: Pre-dose, 7 hours post first dose (prior to second dose) -Day11 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  95. C7 following TID dosing of GSK2982772 240 mg on Day 14 in cohort 3: Part B [ Time Frame: 7 hours post first dose (prior to second dose) -Day14 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  96. Observed trough plasma drug concentration at 14 hours (C14) following TID dosing of GSK2982772 120 mg in cohort 1 : Part A [ Time Frame: 14 hours post first dose (prior to third dose) ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  97. C14 following TID dosing of GSK2982772 240 mg in cohort 1: Part A [ Time Frame: 14 hours post first dose (prior to third dose) ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  98. C14 following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B [ Time Frame: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  99. C14 following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B [ Time Frame: 14 hours post first dose (prior to third dose) -Day14 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  100. C14 following TID dosing of GSK2982772 240 mg on Day 1 in cohort 3: Part B [ Time Frame: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  101. C14 following TID dosing of GSK2982772 240 mg on Day 14 in cohort 3: Part B [ Time Frame: 14 hours post first dose (prior to third dose) -Day14 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  102. Observed trough plasma drug concentration at 24 hours (C24) following TID dosing of GSK2982772 120 mg in cohort 1 : Part A [ Time Frame: 24 hours post first dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  103. C24 following TID dosing of GSK2982772 240 mg in cohort 1: Part A [ Time Frame: 24 hours post first dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  104. C24 following TID dosing of GSK2982772 120 mg on Day 1 in cohort 2: Part B [ Time Frame: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  105. C24 following TID dosing of GSK2982772 120 mg on Day 14 in cohort 2: Part B [ Time Frame: 24 hours post first dose -Day14 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  106. C24 following TID dosing of GSK2982772 240 mg on Day 1 in cohort 3: Part B [ Time Frame: Pre-dose: 20, 40minutes, 1hour, 1hour 30minutes, 2, 3, 5 and 7hours ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  107. C24 following TID dosing of GSK2982772 240 mg on Day 14 in cohort 3: Part B [ Time Frame: 24 hours post first dose -Day14 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  108. C0 following BID dosing of GSK2982772 360 mg in cohort 1 : Part A [ Time Frame: Pre first dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  109. C0 following BID dosing of GSK2982772 360 mg on Day 1 in cohort 4: Part B [ Time Frame: Pre first dose -Day1 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  110. C0 following BID dosing of GSK2982772 360 mg on Day 14 in cohort 4: Part B [ Time Frame: Pre first dose -Day14 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  111. C12 following BID dosing of GSK2982772 360 mg in cohort 1 : Part A [ Time Frame: 12 hours post first dose (prior to second dose) ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  112. C12 following BID dosing of GSK2982772 360 mg on Day 1 in cohort 4: Part B [ Time Frame: 12 hours post first dose (prior to second dose) -Day1 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  113. C12 following BID dosing of GSK2982772 360 mg on Day 14 in cohort 4: Part B [ Time Frame: 12 hours post first dose (prior to second dose) -Day14 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  114. C24 following BID dosing of GSK2982772 360 mg in cohort 1 : Part A [ Time Frame: 24 hours post first dose ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  115. C24 following BID dosing of GSK2982772 360 mg on Day 1 in cohort 4: Part B [ Time Frame: 24 hours post first dose -Day1 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  116. C24 following BID dosing of GSK2982772 360 mg on Day 14 in cohort 4: Part B [ Time Frame: 24 hours post first dose -Day14 ]
    Blood samples will be collected for pharmacokinetic analysis of GSK2982772.

  117. Ratio of plasma 4beta-hydroxycholesterol to cholesterol during pre-treatment and following repeat dosing of GSK2982772: Part B [ Time Frame: Pre-dose on Day 1 and, 24 hours Post first -dose-Day 14 ]
    A comparison will be made between the ratio of 4beta-hydroxycholesterol: cholesterol during pre-treatment and on Day 14 to assess potential changes in cytochrome P450 3A4(CYP3A4) enzyme activity following GSK2982772 treatment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03305419


Locations
United Kingdom
GSK Investigational Site
Cambridge, United Kingdom, CB2 2GG
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03305419     History of Changes
Other Study ID Numbers: 205184
First Posted: October 10, 2017    Key Record Dates
Last Update Posted: March 23, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:
Crossover
Sequential
GSK2982772
Safety
Pharmacokinetics
Healthy subjects

Additional relevant MeSH terms:
Autoimmune Diseases
Immune System Diseases