Trial Outcomes & Findings for Safety, Tolerability and Preliminary Pharmacokinetics (PK) and Pharmacodynamics (PD) of Single and Repeat Oral Doses of GSK3008356 in Healthy and Obese Subjects (NCT NCT02742766)

NCT ID: NCT02742766

Last Updated: 2019-07-24

Results Overview

A complete physical examination included assessment of the cardiovascular, respiratory, gastrointestinal, dermatologic and neurological systems, height, and weight. Height was measured and recorded only at screening. A brief physical examination included assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Weight was recorded with the brief physical exam, but was not part of the brief physical exam. Number of participants with abnormal findings in physical examinations in Part 1 are presented.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 104 participants
• Primary outcome timeframe: Up to Day 8
• Results posted on: 2019-07-24

Participant Flow

A total of 104 participants (80 in Part 1 and 24 in Part 2) were randomized to receive either study medication or placebo. This study was conducted at a single center in Australia from 14-March-2016 to 16-June-2017.

This study was planned to be conducted in 3 parts: Part 1 (single-day dosing) and Part 2 (repeat dose) dose-rising study in healthy participants and Part 3 (repeat dose) in obese participants. Part 3 was not conducted since a tolerable dose with sufficient pharmacodynamic effects was not identified in Part 2 due to gastrointestinal issues.

Participant milestones

Measure	Part 1- Placebo Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 milligrams \[mg\]) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 hour \[h\] and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered once every hour \[q1h\] for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 2-Placebo Eligible participants received GSK3008356 matching placebo tablets via oral route (repeat doses) for a period of 14 days. Day 1 and Day 14 dosing occurred while receiving a standard 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 2-Cohort B1: GSK3008356 10 mg BID (0 h, 16 h) Eligible participants received GSK3008356 tablets twice-daily (BID) via oral route (total daily dose of 20 mg such that a 10 mg dose was administered at 0 h and 16 h) for a period of 14 days. Day 1 and Day 14 dosing occurred while receiving a standard 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 2-Cohort B2: GSK3008356 1 mg BID (0 h, 16 h) Eligible participants received GSK3008356 tablets BID via oral route (total daily dose of 2 mg such that a 1 mg dose was administered at 0 h and 16 h) for a period of 14 days. Day 1 and Day 14 dosing occurred while receiving a standard 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 2-Cohort B3: GSK3008356 3 mg BID (0 h, 16 h) Eligible participants received GSK3008356 tablets BID via oral route (total daily dose of 6 mg such that a 3 mg dose was administered at 0 h and 16 h) for a period of 14 days. Day 1 and Day 14 dosing occurred while receiving a standard 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 3: Obese Participants Cohort 1 Participants in this arm were planned to receive 28 daily doses so as to evaluate 1 dose strength of GSK3008356 (or matching placebo) administered as morning doses. Part 3 was not conducted since a tolerable dose with sufficient pharmacodynamic effects was not identified in Part 2 due to gastrointestinal issues.	Part 3: Obese Participants Cohort 2 Participants in this arm were planned to receive 28 daily doses so as to evaluate 1 dose strength of GSK3008356 (or matching placebo) administered as evening doses. Part 3 was not conducted since a tolerable dose with sufficient pharmacodynamic effects was not identified in Part 2 due to gastrointestinal issues.	Part 3: Obese Participants Cohort 3 Participants in this arm were planned to receive 28 daily doses so as to evaluate 1 dose strength of GSK3008356 (or matching placebo) administered as evening doses. Part 3 was not conducted since a tolerable dose with sufficient pharmacodynamic effects was not identified in Part 2 due to gastrointestinal issues.
Part 1 (Up to 8 Days) STARTED	20	6	6	6	6	6	6	6	6	0	6	6	0	0	0	0	0	0	0
Part 1 (Up to 8 Days) COMPLETED	20	6	6	6	6	6	6	6	6	0	6	6	0	0	0	0	0	0	0
Part 1 (Up to 8 Days) NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Part 2 (Up to 22 Days) STARTED	0	0	0	0	0	0	0	0	0	0	0	0	6	6	6	6	0	0	0
Part 2 (Up to 22 Days) COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	4	0	6	5	0	0	0
Part 2 (Up to 22 Days) NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	2	6	0	1	0	0	0
Part 3 (Up to 36 Days) STARTED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Part 3 (Up to 36 Days) COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Part 3 (Up to 36 Days) NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Reasons for withdrawal

Measure	Part 1- Placebo Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 milligrams \[mg\]) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 hour \[h\] and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered once every hour \[q1h\] for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 2-Placebo Eligible participants received GSK3008356 matching placebo tablets via oral route (repeat doses) for a period of 14 days. Day 1 and Day 14 dosing occurred while receiving a standard 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 2-Cohort B1: GSK3008356 10 mg BID (0 h, 16 h) Eligible participants received GSK3008356 tablets twice-daily (BID) via oral route (total daily dose of 20 mg such that a 10 mg dose was administered at 0 h and 16 h) for a period of 14 days. Day 1 and Day 14 dosing occurred while receiving a standard 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 2-Cohort B2: GSK3008356 1 mg BID (0 h, 16 h) Eligible participants received GSK3008356 tablets BID via oral route (total daily dose of 2 mg such that a 1 mg dose was administered at 0 h and 16 h) for a period of 14 days. Day 1 and Day 14 dosing occurred while receiving a standard 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 2-Cohort B3: GSK3008356 3 mg BID (0 h, 16 h) Eligible participants received GSK3008356 tablets BID via oral route (total daily dose of 6 mg such that a 3 mg dose was administered at 0 h and 16 h) for a period of 14 days. Day 1 and Day 14 dosing occurred while receiving a standard 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 3: Obese Participants Cohort 1 Participants in this arm were planned to receive 28 daily doses so as to evaluate 1 dose strength of GSK3008356 (or matching placebo) administered as morning doses. Part 3 was not conducted since a tolerable dose with sufficient pharmacodynamic effects was not identified in Part 2 due to gastrointestinal issues.	Part 3: Obese Participants Cohort 2 Participants in this arm were planned to receive 28 daily doses so as to evaluate 1 dose strength of GSK3008356 (or matching placebo) administered as evening doses. Part 3 was not conducted since a tolerable dose with sufficient pharmacodynamic effects was not identified in Part 2 due to gastrointestinal issues.	Part 3: Obese Participants Cohort 3 Participants in this arm were planned to receive 28 daily doses so as to evaluate 1 dose strength of GSK3008356 (or matching placebo) administered as evening doses. Part 3 was not conducted since a tolerable dose with sufficient pharmacodynamic effects was not identified in Part 2 due to gastrointestinal issues.
Part 2 (Up to 22 Days) Withdrawal by Subject	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Part 2 (Up to 22 Days) Physician Decision	0	0	0	0	0	0	0	0	0	0	0	0	2	5	0	1	0	0	0

Baseline Characteristics

Safety, Tolerability and Preliminary Pharmacokinetics (PK) and Pharmacodynamics (PD) of Single and Repeat Oral Doses of GSK3008356 in Healthy and Obese Subjects

Baseline characteristics by cohort

Measure	Part 1- Placebo n=20 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg BID (0 h, 4 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg BID (0 h, 16 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 2-Placebo n=6 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (repeat doses) for a period of 14 days. Day 1 and Day 14 dosing occurred while receiving a standard 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 2-Cohort B1: GSK3008356 10 mg BID (0 h, 16 h) n=6 Participants Eligible participants received GSK3008356 tablets BID via oral route (total daily dose of 20 mg such that a 10 mg dose was administered at 0 h and 16 h) for a period of 14 days. Day 1 and Day 14 dosing occurred while receiving a standard 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 2-Cohort B2: GSK3008356 1 mg BID (0 h, 16 h) n=6 Participants Eligible participants received GSK3008356 tablets BID via oral route (total daily dose of 2 mg such that a 1 mg dose was administered at 0 h and 16 h) for a period of 14 days. Day 1 and Day 14 dosing occurred while receiving a standard 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 2-Cohort B3: GSK3008356 3 mg BID (0 h, 16 h) n=6 Participants Eligible participants received GSK3008356 tablets BID via oral route (total daily dose of 6 mg such that a 3 mg dose was administered at 0 h and 16 h) for a period of 14 days. Day 1 and Day 14 dosing occurred while receiving a standard 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 3: Obese Participants Cohort 1 Participants in this arm were planned to receive 28 daily doses so as to evaluate 1 dose strength of GSK3008356 (or matching placebo) administered as morning doses. Part 3 was not conducted since a tolerable dose with sufficient pharmacodynamic effects was not identified in Part 2 due to gastrointestinal issues.	Part 3: Obese Participants Cohort 2 Participants in this arm were planned to receive 28 daily doses so as to evaluate 1 dose strength of GSK3008356 (or matching placebo) administered as evening doses. Part 3 was not conducted since a tolerable dose with sufficient pharmacodynamic effects was not identified in Part 2 due to gastrointestinal issues.	Part 3: Obese Participants Cohort 3 Participants in this arm were planned to receive 28 daily doses so as to evaluate 1 dose strength of GSK3008356 (or matching placebo) administered as evening doses. Part 3 was not conducted since a tolerable dose with sufficient pharmacodynamic effects was not identified in Part 2 due to gastrointestinal issues.	Total n=104 Participants Total of all reporting groups
Age, Continuous	24.8 Years STANDARD_DEVIATION 5.07 • n=93 Participants	28.0 Years STANDARD_DEVIATION 16.49 • n=4 Participants	25.8 Years STANDARD_DEVIATION 3.54 • n=27 Participants	26.3 Years STANDARD_DEVIATION 4.46 • n=483 Participants	26.0 Years STANDARD_DEVIATION 4.69 • n=36 Participants	26.7 Years STANDARD_DEVIATION 5.65 • n=10 Participants	24.3 Years STANDARD_DEVIATION 2.94 • n=115 Participants	28.0 Years STANDARD_DEVIATION 7.04 • n=40 Participants	31.5 Years STANDARD_DEVIATION 4.55 • n=8 Participants	—	26.3 Years STANDARD_DEVIATION 4.76 • n=95 Participants	24.7 Years STANDARD_DEVIATION 3.88 • n=129 Participants	35.3 Years STANDARD_DEVIATION 12.75 • n=36 Participants	26.5 Years STANDARD_DEVIATION 2.59 • n=36 Participants	31.2 Years STANDARD_DEVIATION 11.51 • n=24 Participants	25.8 Years STANDARD_DEVIATION 4.17 • n=135 Participants	—	—	—	27.1 Years STANDARD_DEVIATION 7.18 • n=7 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	—	0 Participants n=95 Participants	0 Participants n=129 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	0 Participants n=135 Participants	—	—	—	0 Participants n=7 Participants
Sex: Female, Male Male	20 Participants n=93 Participants	6 Participants n=4 Participants	6 Participants n=27 Participants	6 Participants n=483 Participants	6 Participants n=36 Participants	6 Participants n=10 Participants	6 Participants n=115 Participants	6 Participants n=40 Participants	6 Participants n=8 Participants	—	6 Participants n=95 Participants	6 Participants n=129 Participants	6 Participants n=36 Participants	6 Participants n=36 Participants	6 Participants n=24 Participants	6 Participants n=135 Participants	—	—	—	104 Participants n=7 Participants
Race/Ethnicity, Customized Asian	3 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	2 Participants n=40 Participants	2 Participants n=8 Participants	—	2 Participants n=95 Participants	1 Participants n=129 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	1 Participants n=135 Participants	—	—	—	12 Participants n=7 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	—	0 Participants n=95 Participants	0 Participants n=129 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	0 Participants n=135 Participants	—	—	—	1 Participants n=7 Participants
Race/Ethnicity, Customized White	15 Participants n=93 Participants	4 Participants n=4 Participants	4 Participants n=27 Participants	5 Participants n=483 Participants	5 Participants n=36 Participants	5 Participants n=10 Participants	5 Participants n=115 Participants	4 Participants n=40 Participants	4 Participants n=8 Participants	—	3 Participants n=95 Participants	4 Participants n=129 Participants	6 Participants n=36 Participants	6 Participants n=36 Participants	5 Participants n=24 Participants	4 Participants n=135 Participants	—	—	—	79 Participants n=7 Participants
Race/Ethnicity, Customized Brazilian	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	—	0 Participants n=95 Participants	0 Participants n=129 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	0 Participants n=135 Participants	—	—	—	2 Participants n=7 Participants
Race/Ethnicity, Customized Chinese/Australian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	—	0 Participants n=95 Participants	0 Participants n=129 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	0 Participants n=135 Participants	—	—	—	1 Participants n=7 Participants
Race/Ethnicity, Customized Egyptian/New Zealand	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	—	0 Participants n=95 Participants	0 Participants n=129 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	0 Participants n=135 Participants	—	—	—	1 Participants n=7 Participants
Race/Ethnicity, Customized Half White Half Italian	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	—	0 Participants n=95 Participants	0 Participants n=129 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	0 Participants n=135 Participants	—	—	—	1 Participants n=7 Participants
Race/Ethnicity, Customized Indian	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	—	0 Participants n=95 Participants	0 Participants n=129 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	0 Participants n=135 Participants	—	—	—	1 Participants n=7 Participants
Race/Ethnicity, Customized Latin	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	—	1 Participants n=95 Participants	1 Participants n=129 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	0 Participants n=135 Participants	—	—	—	2 Participants n=7 Participants
Race/Ethnicity, Customized Moroccan	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	1 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	—	0 Participants n=95 Participants	0 Participants n=129 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	0 Participants n=135 Participants	—	—	—	1 Participants n=7 Participants
Race/Ethnicity, Customized Spanish/Jamaican/English/Irish	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	—	0 Participants n=95 Participants	0 Participants n=129 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	0 Participants n=135 Participants	—	—	—	1 Participants n=7 Participants
Race/Ethnicity, Customized Middle Eastern	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	—	0 Participants n=95 Participants	0 Participants n=129 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	1 Participants n=24 Participants	0 Participants n=135 Participants	—	—	—	1 Participants n=7 Participants
Race/Ethnicity, Customized South American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=40 Participants	0 Participants n=8 Participants	—	0 Participants n=95 Participants	0 Participants n=129 Participants	0 Participants n=36 Participants	0 Participants n=36 Participants	0 Participants n=24 Participants	1 Participants n=135 Participants	—	—	—	1 Participants n=7 Participants

PRIMARY outcome

Timeframe: Up to Day 8

Population: Safety Population comprised of all participants who received at least one dose of study medication.

A complete physical examination included assessment of the cardiovascular, respiratory, gastrointestinal, dermatologic and neurological systems, height, and weight. Height was measured and recorded only at screening. A brief physical examination included assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Weight was recorded with the brief physical exam, but was not part of the brief physical exam. Number of participants with abnormal findings in physical examinations in Part 1 are presented.

Outcome measures

Measure	Part 1- Placebo n=20 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 1: Number of Participants With Abnormal Findings in Physical Examinations	2 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	—	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Day 8

Population: Safety Population.

Vital signs included systolic and diastolic blood pressure and pulse rate and were measured with the participant in semi-supine position after 5 minutes rest. Temperature was also measured as a vital sign but did not require positioning or rest prior to measuring.

Outcome measures

Measure	Part 1- Placebo n=20 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 1: Number of Participants With Vital Signs of Potential Clinical Concern	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to Day 4

Population: Safety Population.

Single 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals, and QT interval corrected by Fridericia's formula (QTcF). Number of participants with 12-lead ECG values of potential clinical concern in Part 1 are presented.

Outcome measures

Measure	Part 1- Placebo n=20 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 1: Number of Participants With 12-lead Electrocardiogram (ECG) Values of Potential Clinical Concern	4 Participants	3 Participants	3 Participants	2 Participants	3 Participants	0 Participants	2 Participants	0 Participants	3 Participants	—	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Day 1

Population: Safety Population.

Continuous lead II cardiac telemetry or cardiac monitoring was performed on Day 1. Number of participants with clinically significant findings during cardiac monitoring in Part 1 are presented.

Outcome measures

Measure	Part 1- Placebo n=20 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 1: Number of Participants With Clinically Significant Findings During Cardiac Monitoring	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Day 8

Population: Safety Population.

Hematology parameters included hematocrit, hemoglobin, platelets, white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red blood cells (RBC) and reticulocytes. Clinical chemistry parameters included blood urea nitrogen, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase, uric acid, total protein, total and direct bilirubin, albumin, calcium, bile acids, chloride, creatinine, glucose (fasting/non-fasting), potassium, sodium and total carbon dioxide/bicarbonate. Urinalysis included specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick and microscopic examination of urine (WBC, RBC and casts) within 120 minutes of collection.

Outcome measures

Measure	Part 1- Placebo n=20 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 1: Number of Participants With Laboratory Values of Potential Clinical Concern	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	—	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to Day 8

Population: Safety Population.

AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant or is associated with liver injury and impaired liver function.

Outcome measures

Measure	Part 1- Placebo n=20 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) AE	5 Participants	2 Participants	1 Participants	1 Participants	3 Participants	4 Participants	4 Participants	3 Participants	3 Participants	—	0 Participants	4 Participants
Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) SAE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Day 22

Population: Safety Population.

A complete physical examination included assessment of the cardiovascular, respiratory, gastrointestinal, dermatologic and neurological systems, height, and weight. Height was measured and recorded only at screening. A brief physical examination included assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Weight was recorded with the brief physical exam, but was not part of the brief physical exam. Number of participants with abnormal findings in physical examinations in Part 2 are presented.

Outcome measures

Measure	Part 1- Placebo n=6 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 2: Number of Participants With Abnormal Findings in Physical Examination	2 Participants	2 Participants	3 Participants	4 Participants	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Up to Day 22

Population: Safety Population.

Vital signs included systolic and diastolic blood pressure and pulse and was measured with the participant in semi-supine position after 5 minutes rest. Temperature was also measured as a vital sign but did not require positioning or rest prior to measuring.

Outcome measures

Measure	Part 1- Placebo n=6 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 2: Number of Participants With Vital Signs of Potential Clinical Concern	1 Participants	0 Participants	0 Participants	1 Participants	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Up to Day 17

Population: Safety Population.

Single 12-lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, and QT intervals, and QTcF. Number of participants with 12-lead ECG values of potential clinical concern in Part 2 are presented.

Outcome measures

Measure	Part 1- Placebo n=6 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 2: Number of Participants With 12-lead ECG Values of Potential Clinical Concern	1 Participants	1 Participants	0 Participants	2 Participants	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Day 1 (Pre-dose to 4 hours post dose)

Population: Safety Population.

Continuous lead II cardiac telemetry or cardiac monitoring was performed on Day 1. Number of participants with clinically significant findings during cardiac monitoring in Part 2 are presented.

Outcome measures

Measure	Part 1- Placebo n=6 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 2: Number of Participants With Clinically Significant Findings During Cardiac Monitoring	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Up to Day 22

Population: Safety Population.

Hematology parameters included hematocrit, hemoglobin, platelets, white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, basophils, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, red blood cells and reticulocytes. Clinical chemistry parameters included blood urea nitrogen, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase, uric acid, total protein, total and direct bilirubin, albumin, calcium, bile acids, chloride, creatinine, glucose (fasting/non-fasting), potassium, sodium and total carbon dioxide/bicarbonate. Urinalysis included specific gravity, potential of hydrogen (pH), glucose, protein, blood and ketones by dipstick and microscopic examination (within 120 minutes of collection).

Outcome measures

Measure	Part 1- Placebo n=6 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 2: Number of Participants With Laboratory Values of Potential Clinical Concern	0 Participants	1 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Up to Day 22

Population: Safety Population.

AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant or is associated with liver injury and impaired liver function.

Outcome measures

Measure	Part 1- Placebo n=6 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 2: Number of Participants With AE and SAE AE	3 Participants	5 Participants	6 Participants	5 Participants	—	—	—	—	—	—	—	—
Part 2: Number of Participants With AE and SAE SAE	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Up to Day 36

Population: Safety Population.

Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to Day 36

Population: Safety Population.

Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to Day 31

Population: Safety Population.

Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Day 1 (Pre-dose to 4 hours post-dose)

Population: Safety Population.

Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to Day 36

Population: Safety Population.

Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: Up to Day 36

Population: Safety Population.

Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18, 24 hours post-dose on Day 1 and 36, 48, and 72 hours post-dose

Population: PK Parameter Population comprised of all participants in the PK Concentration Population (participants for whom a PK sample was obtained and analyzed) who received at least one active dose of GSK3008356 and provided PK parameters. Only those participants available at the specified time points were analyzed.

Blood samples for pharmacokinetic (PK) analysis of GSK3008356 were collected at the indicated time points.

Outcome measures

Measure	Part 1- Placebo n=6 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose n=6 Participants Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 1: Area Under the Concentration-time Curve (AUC) Extrapolated to Infinity (AUC[0 to Inf]), AUC From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0 to t]) and AUC From Time Zero to 24 Hour (AUC[0 to 24]) AUC (0 to inf)	190.004 Hours*nanograms/milliliters Geometric Coefficient of Variation 20.74	313.349 Hours*nanograms/milliliters Geometric Coefficient of Variation 18.23	840.806 Hours*nanograms/milliliters Geometric Coefficient of Variation 27.54	1960.374 Hours*nanograms/milliliters Geometric Coefficient of Variation 14.44	5493.574 Hours*nanograms/milliliters Geometric Coefficient of Variation 17.68	4042.579 Hours*nanograms/milliliters Geometric Coefficient of Variation 40.15	3364.475 Hours*nanograms/milliliters Geometric Coefficient of Variation 271.56	6018.925 Hours*nanograms/milliliters Geometric Coefficient of Variation 44.40	—	3125.413 Hours*nanograms/milliliters Geometric Coefficient of Variation 14.39	1181.752 Hours*nanograms/milliliters Geometric Coefficient of Variation 62.07	—
Part 1: Area Under the Concentration-time Curve (AUC) Extrapolated to Infinity (AUC[0 to Inf]), AUC From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0 to t]) and AUC From Time Zero to 24 Hour (AUC[0 to 24]) AUC (0 to t)	184.934 Hours*nanograms/milliliters Geometric Coefficient of Variation 21.32	307.945 Hours*nanograms/milliliters Geometric Coefficient of Variation 17.76	834.100 Hours*nanograms/milliliters Geometric Coefficient of Variation 27.52	1951.059 Hours*nanograms/milliliters Geometric Coefficient of Variation 14.25	5481.127 Hours*nanograms/milliliters Geometric Coefficient of Variation 17.64	4035.511 Hours*nanograms/milliliters Geometric Coefficient of Variation 40.12	3336.805 Hours*nanograms/milliliters Geometric Coefficient of Variation 277.78	5979.430 Hours*nanograms/milliliters Geometric Coefficient of Variation 44.05	—	3121.146 Hours*nanograms/milliliters Geometric Coefficient of Variation 14.38	1246.797 Hours*nanograms/milliliters Geometric Coefficient of Variation 40.38	—
Part 1: Area Under the Concentration-time Curve (AUC) Extrapolated to Infinity (AUC[0 to Inf]), AUC From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0 to t]) and AUC From Time Zero to 24 Hour (AUC[0 to 24]) AUC (0 to 24)	190.025 Hours*nanograms/milliliters Geometric Coefficient of Variation 20.74	313.369 Hours*nanograms/milliliters Geometric Coefficient of Variation 18.23	840.740 Hours*nanograms/milliliters Geometric Coefficient of Variation 27.54	1957.413 Hours*nanograms/milliliters Geometric Coefficient of Variation 14.11	5454.538 Hours*nanograms/milliliters Geometric Coefficient of Variation 17.24	4036.904 Hours*nanograms/milliliters Geometric Coefficient of Variation 40.09	3352.125 Hours*nanograms/milliliters Geometric Coefficient of Variation 270.66	5552.349 Hours*nanograms/milliliters Geometric Coefficient of Variation 49.03	—	3121.146 Hours*nanograms/milliliters Geometric Coefficient of Variation 14.38	1179.327 Hours*nanograms/milliliters Geometric Coefficient of Variation 61.84	—

SECONDARY outcome

Timeframe: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18, 24 hours post dose on Day 1 and 36, 48, and 72 hours post-dose

Population: PK Parameter Population.

Blood samples for PK analysis of GSK3008356 were collected at the indicated time points.

Outcome measures

Measure	Part 1- Placebo n=6 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose n=6 Participants Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK3008356	92.417 Nanograms per milliliters Geometric Coefficient of Variation 45.40	190.655 Nanograms per milliliters Geometric Coefficient of Variation 22.40	458.496 Nanograms per milliliters Geometric Coefficient of Variation 33.10	890.913 Nanograms per milliliters Geometric Coefficient of Variation 15.87	1865.337 Nanograms per milliliters Geometric Coefficient of Variation 44.38	1568.035 Nanograms per milliliters Geometric Coefficient of Variation 27.58	793.544 Nanograms per milliliters Geometric Coefficient of Variation 260.32	946.060 Nanograms per milliliters Geometric Coefficient of Variation 84.09	—	444.545 Nanograms per milliliters Geometric Coefficient of Variation 19.61	202.817 Nanograms per milliliters Geometric Coefficient of Variation 9.81	—

SECONDARY outcome

Timeframe: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18, 24 hours post dose on Day 1 and 36, 48, and 72 hours post-dose

Population: PK Parameter Population.

Blood samples for PK analysis of GSK3008356 were collected at the indicated time points.

Outcome measures

Measure	Part 1- Placebo n=6 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose n=6 Participants Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 1: Time to Maximum Observed Plasma Concentration (Tmax) of GSK3008356 and Apparent Terminal Half-life (t1/2) of GSK3008356 Tmax	0.833 Hours Standard Deviation 0.4082	0.542 Hours Standard Deviation 0.2458	0.750 Hours Standard Deviation 0.2739	0.756 Hours Standard Deviation 0.2681	0.917 Hours Standard Deviation 0.5845	0.917 Hours Standard Deviation 0.5845	1.667 Hours Standard Deviation 2.1370	3.922 Hours Standard Deviation 6.9303	—	6.225 Hours Standard Deviation 3.0329	6.169 Hours Standard Deviation 2.3376	—
Part 1: Time to Maximum Observed Plasma Concentration (Tmax) of GSK3008356 and Apparent Terminal Half-life (t1/2) of GSK3008356 t1/2	1.501 Hours Standard Deviation 0.2048	1.425 Hours Standard Deviation 0.1885	1.623 Hours Standard Deviation 0.1928	2.113 Hours Standard Deviation 1.2949	4.545 Hours Standard Deviation 3.2092	2.779 Hours Standard Deviation 0.7223	2.540 Hours Standard Deviation 0.6481	1.752 Hours Standard Deviation 0.2470	—	1.992 Hours Standard Deviation 0.2050	1.941 Hours Standard Deviation 0.4058	—

SECONDARY outcome

Timeframe: Pre-dose and over the post-dose intervals 0 to 12 hours and 12 to 24 hours

Population: PK Parameter Population.

Urine samples for PK analysis of GSK3008356 were collected at the indicated time points.

Outcome measures

Measure	Part 1- Placebo n=6 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose n=6 Participants Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 1: Cumulative Amount of Unchanged Drug Excreted Into the Urine (Ae) of GSK3008356	7.958 Nanograms*10^5 Standard Deviation 2.2225	8.699 Nanograms*10^5 Standard Deviation 2.3300	22.738 Nanograms*10^5 Standard Deviation 8.3640	62.332 Nanograms*10^5 Standard Deviation 4.6540	169.051 Nanograms*10^5 Standard Deviation 20.0721	106.273 Nanograms*10^5 Standard Deviation 50.7830	170.777 Nanograms*10^5 Standard Deviation 83.6483	143.269 Nanograms*10^5 Standard Deviation 58.7520	—	91.275 Nanograms*10^5 Standard Deviation 17.8857	28.818 Nanograms*10^5 Standard Deviation 11.7506	—

SECONDARY outcome

Timeframe: Pre-dose and over the post-dose intervals 0 to 12 hours and 12 to 24 hours

Population: PK Parameter Population. Only those participants available at the specified time points were analyzed.

Urine samples for PK analysis of GSK3008356 were collected at the indicated time points.

Outcome measures

Measure	Part 1- Placebo n=6 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose n=6 Participants Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses n=3 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 1: Renal Clearance of Drug From Plasma (CLr) of GSK3008356	4115.667 Milliliters per hour Standard Deviation 855.3612	2752.580 Milliliters per hour Standard Deviation 595.2028	2659.878 Milliliters per hour Standard Deviation 645.2413	3214.711 Milliliters per hour Standard Deviation 539.4800	3091.822 Milliliters per hour Standard Deviation 494.6096	2751.679 Milliliters per hour Standard Deviation 1582.5976	3343.542 Milliliters per hour Standard Deviation 765.2069	2638.871 Milliliters per hour Standard Deviation 2108.5407	—	2935.504 Milliliters per hour Standard Deviation 632.6009	1697.050 Milliliters per hour Standard Deviation 800.8092	—

SECONDARY outcome

Timeframe: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18, 24 hours post-dose on Day 1 and 36, 48, and 72 hours post-dose

Population: PK Parameter Population.

Dose proportionality was assessed from the AUC (0 to t) and AUC (0 to inf) obtained from multiple cohorts in Part 1. The dose proportionality was assessed using a power model on logarithmic transformation of AUC with the logarithmic transformation of dose as the single covariate in the linear regression. Point estimates and 90% confidence interval are presented.

Outcome measures

Measure	Part 1- Placebo n=12 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 1: Dose Proportionality of GSK3008356 for Dose 5 mg Versus (vs.) 200 mg After Single Dose Administration and Multiple Dose Administration (100 mg t0, t4 and 100 mg t0, t16) Based on AUC AUC (0 to t): Cohort A5 vs. Cohort A1	0.92 Slope of log dose Interval 0.86 to 0.97	—	—	—	—	—	—	—	—	—	—	—
Part 1: Dose Proportionality of GSK3008356 for Dose 5 mg Versus (vs.) 200 mg After Single Dose Administration and Multiple Dose Administration (100 mg t0, t4 and 100 mg t0, t16) Based on AUC AUC (0 to t): Cohort A7 vs. Cohort A1	0.78 Slope of log dose Interval 0.49 to 1.08	—	—	—	—	—	—	—	—	—	—	—
Part 1: Dose Proportionality of GSK3008356 for Dose 5 mg Versus (vs.) 200 mg After Single Dose Administration and Multiple Dose Administration (100 mg t0, t4 and 100 mg t0, t16) Based on AUC AUC (0 to t): Cohort A8 vs. Cohort A1	0.94 Slope of log dose Interval 0.85 to 1.04	—	—	—	—	—	—	—	—	—	—	—
Part 1: Dose Proportionality of GSK3008356 for Dose 5 mg Versus (vs.) 200 mg After Single Dose Administration and Multiple Dose Administration (100 mg t0, t4 and 100 mg t0, t16) Based on AUC AUC (0 to inf): Cohort A5 vs. Cohort A1	0.91 Slope of log dose Interval 0.86 to 0.97	—	—	—	—	—	—	—	—	—	—	—
Part 1: Dose Proportionality of GSK3008356 for Dose 5 mg Versus (vs.) 200 mg After Single Dose Administration and Multiple Dose Administration (100 mg t0, t4 and 100 mg t0, t16) Based on AUC AUC (0 to inf): Cohort A7 vs. Cohort A1	0.78 Slope of log dose Interval 0.48 to 1.07	—	—	—	—	—	—	—	—	—	—	—
Part 1: Dose Proportionality of GSK3008356 for Dose 5 mg Versus (vs.) 200 mg After Single Dose Administration and Multiple Dose Administration (100 mg t0, t4 and 100 mg t0, t16) Based on AUC AUC (0 to inf): Cohort A8 vs. Cohort A1	0.94 Slope of log dose Interval 0.84 to 1.03	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18, 24 hours post-dose on Day 1 and 36, 48, and 72 hours post-dose

Population: PK Parameter Population. Only those participants available at the specified time points were analyzed.

Dose proportionality was assessed from the Cmax obtained from multiple cohorts in Part 1. The dose proportionality was assessed using a power model on logarithmic transformation of Cmax, with the logarithmic transformation of dose as the single covariate in the linear regression. For Cmax, only a single dose group from Cohort 1 to Cohort 6 was considered since other cohorts are multiple dosing where Cmax is so different from that of single dose group. Data for Cohort A5 vs. Cohort A1 is presented, Point estimates and 90% confidence interval are presented.

Outcome measures

Measure	Part 1- Placebo n=12 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 1: Dose Proportionality of GSK3008356 for Dose 5 mg vs. 200 mg After Single Dose Administration Based on Cmax	0.81 Slope of log dose Interval 0.69 to 0.94	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 at 1,2,3,4,5,6,7,8,9,12 hours post-dose

Population: Pharmacodynamic (PD) Population comprised of participants in the Safety population for whom at least one postprandial triglyceride sample was obtained and analyzed at Baseline and post Baseline. Only those participants available at the specified time points were analyzed.

Preliminary pharmacodynamics of GSK3008356 was evaluated by assessing the postprandial triglyceride levels at the indicated time points. Corrected triglyceride value (Day 1) at each nominal sampling time point was defined as the corresponding post dose value by adding the following value: Part 1 Day 1 Correction: (Day -1 (1 hour + 2 hour)/2) - (Day 1 (1 hour + 2 hour)/2). Mean triglyceride levels are presented.

Outcome measures

Measure	Part 1- Placebo n=6 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose n=6 Participants Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses n=6 Participants Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 1: Postprandial Triglyceride Levels Following a Single Dose and Multiple Doses of GSK3008356 Day 1, 1 hour post-dose	0.925 Millimoles/Liters Standard Deviation 0.2505	0.900 Millimoles/Liters Standard Deviation 0.3178	0.800 Millimoles/Liters Standard Deviation 0.2168	0.767 Millimoles/Liters Standard Deviation 0.3817	0.742 Millimoles/Liters Standard Deviation 0.4176	1.008 Millimoles/Liters Standard Deviation 0.3470	0.717 Millimoles/Liters Standard Deviation 0.2160	1.242 Millimoles/Liters Standard Deviation 0.4375	—	0.750 Millimoles/Liters Standard Deviation 0.2588	0.775 Millimoles/Liters Standard Deviation 0.2842	—
Part 1: Postprandial Triglyceride Levels Following a Single Dose and Multiple Doses of GSK3008356 Day 1, 2 hour post-dose	0.825 Millimoles/Liters Standard Deviation 0.2505	0.783 Millimoles/Liters Standard Deviation 0.2733	0.700 Millimoles/Liters Standard Deviation 0.2168	0.650 Millimoles/Liters Standard Deviation 0.3317	0.675 Millimoles/Liters Standard Deviation 0.3283	0.875 Millimoles/Liters Standard Deviation 0.3029	0.633 Millimoles/Liters Standard Deviation 0.1992	1.008 Millimoles/Liters Standard Deviation 0.4913	—	0.667 Millimoles/Liters Standard Deviation 0.1966	0.692 Millimoles/Liters Standard Deviation 0.1985	—
Part 1: Postprandial Triglyceride Levels Following a Single Dose and Multiple Doses of GSK3008356 Day 1, 3 hour post-dose	0.825 Millimoles/Liters Standard Deviation 0.2545	0.817 Millimoles/Liters Standard Deviation 0.2338	0.717 Millimoles/Liters Standard Deviation 0.2503	0.667 Millimoles/Liters Standard Deviation 0.2893	0.592 Millimoles/Liters Standard Deviation 0.2691	0.842 Millimoles/Liters Standard Deviation 0.3200	0.750 Millimoles/Liters Standard Deviation 0.2145	1.042 Millimoles/Liters Standard Deviation 0.4954	—	0.667 Millimoles/Liters Standard Deviation 0.2066	0.675 Millimoles/Liters Standard Deviation 0.2162	—
Part 1: Postprandial Triglyceride Levels Following a Single Dose and Multiple Doses of GSK3008356 Day 1, 4 hour post-dose	1.058 Millimoles/Liters Standard Deviation 0.3056	0.733 Millimoles/Liters Standard Deviation 0.2273	0.783 Millimoles/Liters Standard Deviation 0.2805	0.617 Millimoles/Liters Standard Deviation 0.2696	0.508 Millimoles/Liters Standard Deviation 0.2538	0.792 Millimoles/Liters Standard Deviation 0.2333	0.783 Millimoles/Liters Standard Deviation 0.2910	0.875 Millimoles/Liters Standard Deviation 0.4084	—	0.600 Millimoles/Liters Standard Deviation 0.2000	0.592 Millimoles/Liters Standard Deviation 0.2635	—
Part 1: Postprandial Triglyceride Levels Following a Single Dose and Multiple Doses of GSK3008356 Day 1, 5 hour post-dose	1.308 Millimoles/Liters Standard Deviation 0.4092	0.867 Millimoles/Liters Standard Deviation 0.2714	0.950 Millimoles/Liters Standard Deviation 0.2864	0.767 Millimoles/Liters Standard Deviation 0.3281	0.558 Millimoles/Liters Standard Deviation 0.3007	0.825 Millimoles/Liters Standard Deviation 0.1994	1.000 Millimoles/Liters Standard Deviation 0.5320	0.958 Millimoles/Liters Standard Deviation 0.4188	—	0.617 Millimoles/Liters Standard Deviation 0.1780	0.608 Millimoles/Liters Standard Deviation 0.3024	—
Part 1: Postprandial Triglyceride Levels Following a Single Dose and Multiple Doses of GSK3008356 Day 1, 6 hour post-dose	1.425 Millimoles/Liters Standard Deviation 0.4612	0.983 Millimoles/Liters Standard Deviation 0.3531	1.017 Millimoles/Liters Standard Deviation 0.3502	0.817 Millimoles/Liters Standard Deviation 0.2582	0.625 Millimoles/Liters Standard Deviation 0.3126	0.842 Millimoles/Liters Standard Deviation 0.2836	1.017 Millimoles/Liters Standard Deviation 0.5663	1.075 Millimoles/Liters Standard Deviation 0.5223	—	0.700 Millimoles/Liters Standard Deviation 0.1949	0.642 Millimoles/Liters Standard Deviation 0.3427	—
Part 1: Postprandial Triglyceride Levels Following a Single Dose and Multiple Doses of GSK3008356 Day 1, 7 hour post-dose	1.275 Millimoles/Liters Standard Deviation 0.4783	0.967 Millimoles/Liters Standard Deviation 0.3601	0.950 Millimoles/Liters Standard Deviation 0.3493	0.850 Millimoles/Liters Standard Deviation 0.2608	0.658 Millimoles/Liters Standard Deviation 0.3639	0.842 Millimoles/Liters Standard Deviation 0.2289	0.917 Millimoles/Liters Standard Deviation 0.5663	1.175 Millimoles/Liters Standard Deviation 0.5681	—	0.700 Millimoles/Liters Standard Deviation 0.2098	0.608 Millimoles/Liters Standard Deviation 0.2923	—
Part 1: Postprandial Triglyceride Levels Following a Single Dose and Multiple Doses of GSK3008356 Day 1, 8 hour post-dose	1.158 Millimoles/Liters Standard Deviation 0.4018	0.833 Millimoles/Liters Standard Deviation 0.3093	0.850 Millimoles/Liters Standard Deviation 0.3464	0.850 Millimoles/Liters Standard Deviation 0.2000	0.692 Millimoles/Liters Standard Deviation 0.4104	0.925 Millimoles/Liters Standard Deviation 0.2444	0.883 Millimoles/Liters Standard Deviation 0.4782	1.258 Millimoles/Liters Standard Deviation 0.6078	—	0.670 Millimoles/Liters Standard Deviation 0.2197	0.592 Millimoles/Liters Standard Deviation 0.3541	—
Part 1: Postprandial Triglyceride Levels Following a Single Dose and Multiple Doses of GSK3008356 Day 1, 9 hour post-dose	1.008 Millimoles/Liters Standard Deviation 0.4042	0.750 Millimoles/Liters Standard Deviation 0.2683	0.733 Millimoles/Liters Standard Deviation 0.3573	0.767 Millimoles/Liters Standard Deviation 0.1722	0.675 Millimoles/Liters Standard Deviation 0.3947	0.858 Millimoles/Liters Standard Deviation 0.2905	0.850 Millimoles/Liters Standard Deviation 0.4450	1.292 Millimoles/Liters Standard Deviation 0.4893	—	0.617 Millimoles/Liters Standard Deviation 0.2714	0.658 Millimoles/Liters Standard Deviation 0.3484	—
Part 1: Postprandial Triglyceride Levels Following a Single Dose and Multiple Doses of GSK3008356 Day 1, 12 hour post-dose	0.725 Millimoles/Liters Standard Deviation 0.2697	0.583 Millimoles/Liters Standard Deviation 0.1693	0.700 Millimoles/Liters Standard Deviation 0.3178	0.667 Millimoles/Liters Standard Deviation 0.2090	0.775 Millimoles/Liters Standard Deviation 0.4263	0.925 Millimoles/Liters Standard Deviation 0.2525	0.883 Millimoles/Liters Standard Deviation 0.3173	1.025 Millimoles/Liters Standard Deviation 0.3984	—	0.700 Millimoles/Liters Standard Deviation 0.2236	0.792 Millimoles/Liters Standard Deviation 0.3247	—

SECONDARY outcome

Timeframe: Day 1 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24 hours post-dose, pre-dose Day 4, 5, 6, 12 and 13 and Day 14 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24, 36, 48 and 72 hours post dose

Population: PK Parameter Population. Only those participants available at the specified time points were analyzed.

Blood samples for PK analysis of GSK3008356 were collected at the indicated time points. Due to the cancellation of Part 2, Cohort B1, there are no PK parameters available on Day 14 for that dose.

Outcome measures

Measure	Part 1- Placebo n=6 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 2: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the End of Dosing Interval (AUC[0 to Tau]) of GSK3008356 on Day 1 and Day 14 AUC (0 to tau) on Day 1	279.222 Hours*nanograms/milliliters Geometric Coefficient of Variation 26.39	31.959 Hours*nanograms/milliliters Geometric Coefficient of Variation 25.16	107.191 Hours*nanograms/milliliters Geometric Coefficient of Variation 32.12	—	—	—	—	—	—	—	—	—
Part 2: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the End of Dosing Interval (AUC[0 to Tau]) of GSK3008356 on Day 1 and Day 14 AUC (0 to tau) on Day 14	—	37.429 Hours*nanograms/milliliters Geometric Coefficient of Variation 21.97	101.151 Hours*nanograms/milliliters Geometric Coefficient of Variation 20.20	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24 hours post-dose, pre-dose Day 4, 5, 6, 12 and 13 and Day 14 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24, 36, 48 and 72 hours post dose

Population: PK Parameter Population. Only those participants available at the specified time points were analyzed.

Blood samples for PK analysis of GSK3008356 were collected at the indicated time points. Due to the cancellation of Part 2, Cohort B1, there are no PK parameters available on Day 14 for that dose.

Outcome measures

Measure	Part 1- Placebo n=6 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 2: Cmax of GSK3008356 on Day 1 and Day 14 Day 1	187.032 Nanograms/milliliters Geometric Coefficient of Variation 28.69	17.638 Nanograms/milliliters Geometric Coefficient of Variation 40.02	77.326 Nanograms/milliliters Geometric Coefficient of Variation 31.73	—	—	—	—	—	—	—	—	—
Part 2: Cmax of GSK3008356 on Day 1 and Day 14 Day 14	—	16.424 Nanograms/milliliters Geometric Coefficient of Variation 33.86	46.736 Nanograms/milliliters Geometric Coefficient of Variation 17.52	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24 hours post-dose, pre-dose Day 4, 5, 6, 12 and 13 and Day 14 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24, 36, 48 and 72 hours post dose

Population: PK Parameter Population. Only those participants available at the specified time points were analyzed.

Blood samples for PK analysis of GSK3008356 were collected at the indicated time points. Due to the cancellation of Part 2, Cohort B1, there are no PK parameters available on Day 14 for that dose.

Outcome measures

Measure	Part 1- Placebo n=6 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 2: t1/2 and Tmax of GSK3008356 on Day 1 and Day 14 Tmax on Day 14	—	0.875 Hours Standard Deviation 0.6275	0.550 Hours Standard Deviation 0.2739	—	—	—	—	—	—	—	—	—
Part 2: t1/2 and Tmax of GSK3008356 on Day 1 and Day 14 t1/2 on Day 1	1.319 Hours Standard Deviation 0.1512	1.312 Hours Standard Deviation 0.1369	1.443 Hours Standard Deviation 0.1624	—	—	—	—	—	—	—	—	—
Part 2: t1/2 and Tmax of GSK3008356 on Day 1 and Day 14 t1/2 on Day 14	—	1.406 Hours Standard Deviation 0.2138	2.115 Hours Standard Deviation 1.3252	—	—	—	—	—	—	—	—	—
Part 2: t1/2 and Tmax of GSK3008356 on Day 1 and Day 14 Tmax on Day 1	0.517 Hours Standard Deviation 0.0279	0.583 Hours Standard Deviation 0.2041	0.436 Hours Standard Deviation 0.1511	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Pre-dose and 24 hours post-dose on Day 14

Population: PK Parameter Population.

Urine samples (urine concentrations or volumes) were not collected for the Part 2 of the study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose and 24 hours post-dose on Day 14

Population: PK Parameter Population.

Urine samples (urine concentrations or volumes) were not collected for the Part 2 of the study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24 hours post-dose, pre-dose Day 4, 5, 6, 12 and 13 and Day 14 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24, 36, 48 and 72 hours post dose

Population: PK Parameter Population. Only those parameters available at the specified time points were analyzed.

Dose proportionality was assessed from Day 1 and Day 14 AUC (0 to tau) obtained from multiple cohorts in Part 2. The dose proportionality was assessed using a power model on logarithmic transformation of AUC, with the logarithmic transformation of dose as the single covariate in the linear regression. Due to the cancellation of Part 2, Cohort B1, there are no PK parameters available on Day 14 for that dose. Point estimates and 90% confidence interval are presented.

Outcome measures

Measure	Part 1- Placebo n=12 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 2: Dose Proportionality of GSK3008356 for Dose 1 mg BID vs 10 mg BID and 3 mg BID After Repeat Dose Administration Based on AUC AUC (0 to tau); Cohort B1 vs. Cohort B2 on Day 1	0.94 Slope of log dose Interval 0.83 to 1.06	—	—	—	—	—	—	—	—	—	—	—
Part 2: Dose Proportionality of GSK3008356 for Dose 1 mg BID vs 10 mg BID and 3 mg BID After Repeat Dose Administration Based on AUC AUC (0 to tau); Cohort B3 vs. Cohort B2 on Day 1	1.10 Slope of log dose Interval 0.83 to 1.37	—	—	—	—	—	—	—	—	—	—	—
Part 2: Dose Proportionality of GSK3008356 for Dose 1 mg BID vs 10 mg BID and 3 mg BID After Repeat Dose Administration Based on AUC AUC (0 to tau); Cohort B3 vs. Cohort B2 on Day 14	0.90 Slope of log dose Interval 0.69 to 1.12	—	—	—	—	—	—	—	—	—	—	—
Part 2: Dose Proportionality of GSK3008356 for Dose 1 mg BID vs 10 mg BID and 3 mg BID After Repeat Dose Administration Based on AUC AUC (0 to inf); Cohort B1 vs. Cohort B2 on Day 1	0.94 Slope of log dose Interval 0.83 to 1.06	—	—	—	—	—	—	—	—	—	—	—
Part 2: Dose Proportionality of GSK3008356 for Dose 1 mg BID vs 10 mg BID and 3 mg BID After Repeat Dose Administration Based on AUC AUC (0 to inf); Cohort B3 vs. Cohort B2 on Day 1	1.10 Slope of log dose Interval 0.83 to 1.37	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24 hours post-dose, pre-dose Day 4, 5, 6, 12 and 13 and Day 14 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24, 36, 48 and 72 hours post-dose

Population: PK Parameter Population.

The dose proportionality was assessed using a power model on logarithmic transformation of Cmax, with the logarithmic transformation of dose as the single covariate in the linear regression. Due to the cancellation of Part 2, Cohort B1, there are no PK parameters available on Day 14 for that dose. Point estimates and 90% confidence interval are presented for Day 1 and Day 14 of Part 2.

Outcome measures

Measure	Part 1- Placebo n=12 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 2: Dose Proportionality of GSK3008356 for Dose 1 mg BID vs 10 mg BID and 3 mg BID After Repeat Dose Administration Based on Cmax Cmax; Cohort B1 vs. Cohort B2 on Day 1	1.03 Slope of log dose Interval 0.87 to 1.18	—	—	—	—	—	—	—	—	—	—	—
Part 2: Dose Proportionality of GSK3008356 for Dose 1 mg BID vs 10 mg BID and 3 mg BID After Repeat Dose Administration Based on Cmax Cmax; Cohort B3 vs. Cohort B2 on Day 1	1.35 Slope of log dose Interval 1.01 to 1.68	—	—	—	—	—	—	—	—	—	—	—
Part 2: Dose Proportionality of GSK3008356 for Dose 1 mg BID vs 10 mg BID and 3 mg BID After Repeat Dose Administration Based on Cmax Cmax; Cohort B3 vs. Cohort B2 on Day 14	0.95 Slope of log dose Interval 0.68 to 1.23	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24 hours post-dose, pre-dose Day 4, 5, 6, 12 and 13 and Day 14 pre-dose, and 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 18 and 24, 36, 48 and 72 hours post dose

Population: PK Parameter Population. Only those participants available at the specified time points were analyzed.

Observed accumulation ratio based on AUC(0- tau) is (Ro), and based on Cmax is (RCmax). Ro was calculated as the ratio [AUC0-tau on the final day (Day 14)]/[ AUC0-tau on Day 1] and Rcmax was calculated as the ratio [Cmax on the final day (Day 14)]/[Cmax on Day 1]. Blood samples for PK analysis of GSK3008356 were collected at the indicated time points.

Outcome measures

Measure	Part 1- Placebo Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=5 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 2: Observed Accumulation Ratio of GSK3008356 Ro	—	1.171 Ratio Geometric Coefficient of Variation 13.52	1.010 Ratio Geometric Coefficient of Variation 19.76	—	—	—	—	—	—	—	—	—
Part 2: Observed Accumulation Ratio of GSK3008356 Rcmax	—	0.931 Ratio Geometric Coefficient of Variation 22.64	0.606 Ratio Geometric Coefficient of Variation 38.82	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Pre-dose on Days 2, 4, 5, 6, 12, 13, 14 and the 24 hours post-dose on Day 14

Population: PK Parameter Population. Only those participants available at the specified time points were analyzed.

Ctrough is the observed concentration at the end of a dosing interval, immediately before next administration. Due to the cancellation of Part 2, Cohort B1, there are no PK parameters available on Day 14 for that dose.

Outcome measures

Measure	Part 1- Placebo n=6 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 2: Trough Plasma Concentrations (Ctrough) to Assess Steady State of GSK3008356 Following 14-day Repeat Dosing Day 1, 24 Hour	11.953 Nanograms/Milliliters Standard Deviation 7.8239	2.595 Nanograms/Milliliters Standard Deviation 2.0718	4.025 Nanograms/Milliliters Standard Deviation 1.7353	—	—	—	—	—	—	—	—	—
Part 2: Trough Plasma Concentrations (Ctrough) to Assess Steady State of GSK3008356 Following 14-day Repeat Dosing Day 4, Pre-Dose	11.528 Nanograms/Milliliters Standard Deviation 7.2515	1.362 Nanograms/Milliliters Standard Deviation 0.7706	1.940 Nanograms/Milliliters Standard Deviation 2.2364	—	—	—	—	—	—	—	—	—
Part 2: Trough Plasma Concentrations (Ctrough) to Assess Steady State of GSK3008356 Following 14-day Repeat Dosing Day 5, Pre-Dose	4.790 Nanograms/Milliliters Standard Deviation 2.2425	1.392 Nanograms/Milliliters Standard Deviation 1.6697	6.595 Nanograms/Milliliters Standard Deviation 4.8009	—	—	—	—	—	—	—	—	—
Part 2: Trough Plasma Concentrations (Ctrough) to Assess Steady State of GSK3008356 Following 14-day Repeat Dosing Day 6, Pre-Dose	2.880 Nanograms/Milliliters Standard Deviation 2.6985	0.475 Nanograms/Milliliters Standard Deviation 0.7364	3.206 Nanograms/Milliliters Standard Deviation 1.9157	—	—	—	—	—	—	—	—	—
Part 2: Trough Plasma Concentrations (Ctrough) to Assess Steady State of GSK3008356 Following 14-day Repeat Dosing Day 12, Pre-Dose	—	0.205 Nanograms/Milliliters Standard Deviation 0.5021	1.934 Nanograms/Milliliters Standard Deviation 1.0154	—	—	—	—	—	—	—	—	—
Part 2: Trough Plasma Concentrations (Ctrough) to Assess Steady State of GSK3008356 Following 14-day Repeat Dosing Day 13, Pre-Dose	—	0.325 Nanograms/Milliliters Standard Deviation 0.7961	3.756 Nanograms/Milliliters Standard Deviation 2.1434	—	—	—	—	—	—	—	—	—
Part 2: Trough Plasma Concentrations (Ctrough) to Assess Steady State of GSK3008356 Following 14-day Repeat Dosing Day 14, Pre-Dose	—	1.587 Nanograms/Milliliters Standard Deviation 1.3835	4.368 Nanograms/Milliliters Standard Deviation 3.3806	—	—	—	—	—	—	—	—	—
Part 2: Trough Plasma Concentrations (Ctrough) to Assess Steady State of GSK3008356 Following 14-day Repeat Dosing Day 14, 24 Hour	—	1.420 Nanograms/Milliliters Standard Deviation 0.6255	1.866 Nanograms/Milliliters Standard Deviation 0.4191	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 (1, 2, 3, 4, 5, 6, 7, 8, 9 and 12 hours post-dose) and Day 14 (1, 2, 3, 4, 5, 6, 7, 8, 9 and 12 hours post-dose)

Population: PD Population. Only those participants available at the specified time points were analyzed.

Preliminary pharmacodynamics of GSK3008356 was evaluated by assessing the postprandial triglyceride levels at the indicated time points. Corrected TG value (Day 1 and Day 14) at each nominal sampling time point defined as the corresponding post dose value by adding the following value: Part 2 Day 1 Correction: (Day -1 (1 hour + 2 hour)/2) - (Day 1 (1 hour + 2 hour)/2); Part 2 Day 14 Correction: (Day -1 (1 hour + 2 hour)/2) - (Day 14 (1 hour + 2 hour)/2). Mean triglyceride levels are presented.

Outcome measures

Measure	Part 1- Placebo n=6 Participants Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 Participants Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg (0 h, 4 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A8: GSK3008356 100 mg (0 h, 16 h) Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 14, 8 hour post-dose	—	1.367 Millimoles/Liter Standard Deviation 0.4834	1.380 Millimoles/Liter Standard Deviation 0.4764	—	—	—	—	—	—	—	—	—
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 1, 1 hour post-dose	0.867 Millimoles/Liter Standard Deviation 0.4987	0.950 Millimoles/Liter Standard Deviation 0.3017	1.217 Millimoles/Liter Standard Deviation 0.3697	—	—	—	—	—	—	—	—	—
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 1, 2 hour post-dose	0.800 Millimoles/Liter Standard Deviation 0.4219	0.783 Millimoles/Liter Standard Deviation 0.2317	0.950 Millimoles/Liter Standard Deviation 0.2236	—	—	—	—	—	—	—	—	—
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 1, 5 hour post-dose	1.033 Millimoles/Liter Standard Deviation 0.4633	1.017 Millimoles/Liter Standard Deviation 0.4309	1.317 Millimoles/Liter Standard Deviation 0.4655	—	—	—	—	—	—	—	—	—
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 1, 6 hour post-dose	1.150 Millimoles/Liter Standard Deviation 0.4990	1.050 Millimoles/Liter Standard Deviation 0.6189	1.500 Millimoles/Liter Standard Deviation 0.5523	—	—	—	—	—	—	—	—	—
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 1, 3 hour post-dose	0.767 Millimoles/Liter Standard Deviation 0.4987	0.883 Millimoles/Liter Standard Deviation 0.3189	0.983 Millimoles/Liter Standard Deviation 0.2503	—	—	—	—	—	—	—	—	—
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 1, 4 hour post-dose	0.883 Millimoles/Liter Standard Deviation 0.4956	0.833 Millimoles/Liter Standard Deviation 0.3235	1.067 Millimoles/Liter Standard Deviation 0.3220	—	—	—	—	—	—	—	—	—
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 1, 7 hour post-dose	1.300 Millimoles/Liter Standard Deviation 0.5933	1.233 Millimoles/Liter Standard Deviation 0.7005	1.700 Millimoles/Liter Standard Deviation 0.3987	—	—	—	—	—	—	—	—	—
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 1, 8 hour post-dose	1.283 Millimoles/Liter Standard Deviation 0.7561	1.167 Millimoles/Liter Standard Deviation 0.6578	1.717 Millimoles/Liter Standard Deviation 0.4676	—	—	—	—	—	—	—	—	—
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 1, 9 hour post-dose	1.050 Millimoles/Liter Standard Deviation 0.6442	1.000 Millimoles/Liter Standard Deviation 0.6293	1.467 Millimoles/Liter Standard Deviation 0.5037	—	—	—	—	—	—	—	—	—
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 1, 12 hour post-dose	0.800 Millimoles/Liter Standard Deviation 0.4359	0.717 Millimoles/Liter Standard Deviation 0.3996	1.033 Millimoles/Liter Standard Deviation 0.2041	—	—	—	—	—	—	—	—	—
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 14, 1 hour post-dose	—	0.917 Millimoles/Liter Standard Deviation 0.3077	1.020 Millimoles/Liter Standard Deviation 0.2490	—	—	—	—	—	—	—	—	—
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 14, 2 hour post-dose	—	0.817 Millimoles/Liter Standard Deviation 0.2582	0.960 Millimoles/Liter Standard Deviation 0.1597	—	—	—	—	—	—	—	—	—
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 14, 3 hour post-dose	—	0.950 Millimoles/Liter Standard Deviation 0.2757	1.080 Millimoles/Liter Standard Deviation 0.1924	—	—	—	—	—	—	—	—	—
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 14, 4 hour post-dose	—	1.017 Millimoles/Liter Standard Deviation 0.2840	1.020 Millimoles/Liter Standard Deviation 0.2907	—	—	—	—	—	—	—	—	—
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 14, 5 hour post-dose	—	1.100 Millimoles/Liter Standard Deviation 0.3860	1.060 Millimoles/Liter Standard Deviation 0.2748	—	—	—	—	—	—	—	—	—
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 14, 6 hour post-dose	—	1.217 Millimoles/Liter Standard Deviation 0.5066	1.260 Millimoles/Liter Standard Deviation 0.3943	—	—	—	—	—	—	—	—	—
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 14, 7 hour post-dose	—	1.367 Millimoles/Liter Standard Deviation 0.5345	1.460 Millimoles/Liter Standard Deviation 0.2608	—	—	—	—	—	—	—	—	—
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 14, 9 hour post-dose	—	0.817 Millimoles/Liter Standard Deviation 0.4844	1.220 Millimoles/Liter Standard Deviation 0.5239	—	—	—	—	—	—	—	—	—
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356 Day 14, 12 hour post-dose	—	0.800 Millimoles/Liter Standard Deviation 0.4889	0.720 Millimoles/Liter Standard Deviation 0.6079	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8 (only in cohort 1), 12, 14 (only in cohorts 2 and 3), 18, and 24 hours post-dose on Day 1 and Day 28 and additionally 36, 48, and 72 hours post-dose on Day 28

Population: PK Parameter Population.

Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8 (only in cohort 1), 12, 14 (only in cohorts 2 and 3), 18, and 24 hours post-dose on Day 1 and Day 28 and additionally 36, 48, and 72 hours post-dose on Day 28

Population: PK Parameter Population.

Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8 (only in cohort 1), 12, 14 (only in cohorts 2 and 3), 18, and 24 hours post-dose on Day 1 and Day 28 and additionally 36, 48, and 72 hours post-dose on Day 28

Population: PK Parameter Population.

Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8 (only in cohort 1), 12, 14 (only in cohorts 2 and 3), 18, 24, 36, 48, and 72 hours post-dose on Day 28

Population: PK Parameter Population.

Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 28 in each cohort

Population: PK Parameter Population.

Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 28 in each cohort

Population: PK Parameter Population.

Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8 (only in cohort 1), 12, 14 (only in cohorts 2 and 3), 18, and 24 hours post-dose on Days 1 and 28 and additionally 36, 48, and 72 hours post-dose on Day 28

Population: PK Parameter Population.

Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8 (only in cohort 1), 12, 14 (only in cohorts 2 and 3), 18, and 24 hours post-dose on Days 1 and 28 and additionally 36, 48, and 72 hours post-dose on Day 28

Population: PK Parameter Population.

Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8 (only in cohort 1), 12, 14 (only in cohorts 2 and 3), 18, and 24 hours post-dose on Days 1 and 28 and additionally 36, 48, and 72 hours post-dose on Day 28

Population: PK Parameter Population.

Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day -1, Day 1, and Day 28 in cohort 1, and Day 1, Day 2, and Day 28 in cohorts 2 and 3

Population: PD Population.

Part 3 was planned as a 28-day, repeat dose study in obese participants; however, since a tolerable dose with sufficient pharmacodynamic effects was not identified, this portion of the study was not conducted.

Outcome measures

Outcome data not reported

Adverse Events

Part 1-Cohort A8: GSK3008356 100 mg BID (0 h, 16 h)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part 1-Cohort A9: GSK3008356 200 mg Evening Dose

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Part 1- Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Part 1-Cohort A1: GSK3008356 5 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part 1-Cohort A2: GSK3008356 10 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Part 1-Cohort A3: GSK3008356 30 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part 1-Cohort A4: GSK3008356 75 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part 1-Cohort A5: GSK3008356 200 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part 1-Cohort A6: GSK3008356 125 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part 1-Cohort A7: GSK3008356 100 mg BID (0 h, 4 h)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part 2-Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part 2-Cohort B1: GSK3008356 10 mg BID (0 h, 16 h)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Part 2-Cohort B2: GSK3008356 1 mg BID (0 h, 16 h)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part 2-Cohort B3: GSK3008356 3 mg BID (0 h, 16 h)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part 3: Obese Participants Cohort 1

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Part 3: Obese Participants Cohort 2

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Part 3: Obese Participants Cohort 3

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Part 1-Cohort A8: GSK3008356 100 mg BID (0 h, 16 h) n=6 participants at risk Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 16 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A9: GSK3008356 200 mg Evening Dose Participants in this arm were planned to receive a single evening dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the evening dose; but this arm was cancelled.	Part 1- Placebo n=20 participants at risk Eligible participants received GSK3008356 matching placebo tablets via oral route (as either single or multiple doses) along with a 30% fat by calorie meal approximately 2 hours after the morning dose for a single day.	Part 1-Cohort A1: GSK3008356 5 mg n=6 participants at risk Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 5 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A2: GSK3008356 10 mg n=6 participants at risk Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 10 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A3: GSK3008356 30 mg n=6 participants at risk Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 30 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A4: GSK3008356 75 mg n=6 participants at risk Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 75 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A5: GSK3008356 200 mg n=6 participants at risk Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 200 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A6: GSK3008356 125 mg n=6 participants at risk Eligible participants received a single morning dose of GSK3008356 tablets via oral route (total dose of 125 mg) along with a 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 1-Cohort A7: GSK3008356 100 mg BID (0 h, 4 h) n=6 participants at risk Eligible participants received GSK3008356 tablets via oral route (total dose of 200 mg such that one 100 mg dose was administered at 0 h and 4 h) along with a 30% fat by calorie meal approximately 2 hours after the morning dose in a single day.	Part 1-Cohort A10: GSK3008356 10 mg q1h x 9 Doses n=6 participants at risk Eligible participants received GSK3008356 tablets via oral route (total dose of 90 mg such that a 10 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 1-Cohort A11: GSK3008356 5 mg q1h x 9 Doses n=6 participants at risk Eligible participants received GSK3008356 tablets via oral route (total dose of 45 mg such that a 5 mg dose was administered q1h for a total of 9 doses) along with a 30% fat by calorie meal approximately 2 hours after the first morning dose in a single day.	Part 2-Placebo n=6 participants at risk Eligible participants received GSK3008356 matching placebo tablets via oral route (repeat doses) for a period of 14 days. Day 1 and Day 14 dosing occurred while receiving a standard 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 2-Cohort B1: GSK3008356 10 mg BID (0 h, 16 h) n=6 participants at risk Eligible participants received GSK3008356 tablets BID via oral route (total daily dose of 20 mg such that a 10 mg dose was administered at 0 h and 16 h) for a period of 14 days. Day 1 and Day 14 dosing occurred while receiving a standard 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 2-Cohort B2: GSK3008356 1 mg BID (0 h, 16 h) n=6 participants at risk Eligible participants received GSK3008356 tablets BID via oral route (total daily dose of 2 mg such that a 1 mg dose was administered at 0 h and 16 h) for a period of 14 days. Day 1 and Day 14 dosing occurred while receiving a standard 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 2-Cohort B3: GSK3008356 3 mg BID (0 h, 16 h) n=6 participants at risk Eligible participants received GSK3008356 tablets BID via oral route (total daily dose of 6 mg such that a 3 mg dose was administered at 0 h and 16 h) for a period of 14 days. Day 1 and Day 14 dosing occurred while receiving a standard 30% fat by calorie meal approximately 2 hours after the morning dose.	Part 3: Obese Participants Cohort 1 Participants in this arm were planned to receive 28 daily doses so as to evaluate 1 dose strength of GSK3008356 (or matching placebo) administered as morning doses. Part 3 was not conducted since a tolerable dose with sufficient pharmacodynamic effects was not identified in Part 2 due to gastrointestinal issues.	Part 3: Obese Participants Cohort 2 Participants in this arm were planned to receive 28 daily doses so as to evaluate 1 dose strength of GSK3008356 (or matching placebo) administered as evening doses. Part 3 was not conducted since a tolerable dose with sufficient pharmacodynamic effects was not identified in Part 2 due to gastrointestinal issues.	Part 3: Obese Participants Cohort 3 Participants in this arm were planned to receive 28 daily doses so as to evaluate 1 dose strength of GSK3008356 (or matching placebo) administered as evening doses. Part 3 was not conducted since a tolerable dose with sufficient pharmacodynamic effects was not identified in Part 2 due to gastrointestinal issues.
Gastrointestinal disorders Nausea	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/20 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	50.0% 3/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	83.3% 5/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	50.0% 3/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.
Gastrointestinal disorders Vomiting	33.3% 2/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/20 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	33.3% 2/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.
Gastrointestinal disorders Diarrhoea	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/20 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	33.3% 2/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	33.3% 2/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	33.3% 2/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	66.7% 4/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	50.0% 3/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/20 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	50.0% 3/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.
Nervous system disorders Headache	33.3% 2/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/20 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	33.3% 2/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	50.0% 3/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.
Nervous system disorders Dizziness	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/20 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	33.3% 2/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	16.7% 1/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	0.00% 0/6 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.	— 0/0 • Serious adverse events and non-serious adverse events were collected from the start of study treatment until the follow-up contact (Up to 8 days for Part 1 and up to 22 days for Part 2) Serious adverse events and non-serious adverse events were collected for the Safety Population which comprised of all participants who received at least one dose of study medication. Non-serious adverse events and serious adverse events were not collected in Part 3 as no participants were enrolled. All non-serious adverse events with a frequency threshold of more than 3 occurrences in any part is presented.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: GSKClinicalSupportHD@gsk.com

Results disclosure agreements

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

Restriction type: OTHER