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.
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Part 1 (Up to 8 Days)
STARTED
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20
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6
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6
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6
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6
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6
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6
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6
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0
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6
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Part 1 (Up to 8 Days)
COMPLETED
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20
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6
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6
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6
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6
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6
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6
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6
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0
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Part 1 (Up to 8 Days)
NOT COMPLETED
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0
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Part 2 (Up to 22 Days)
STARTED
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6
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6
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Part 2 (Up to 22 Days)
COMPLETED
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0
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4
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6
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5
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Part 2 (Up to 22 Days)
NOT COMPLETED
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0
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0
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0
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2
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6
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0
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1
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0
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0
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0
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Part 3 (Up to 36 Days)
STARTED
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0
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0
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0
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0
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0
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0
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Part 3 (Up to 36 Days)
COMPLETED
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0
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0
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Part 3 (Up to 36 Days)
NOT COMPLETED
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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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
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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1
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0
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0
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0
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0
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0
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Part 2 (Up to 22 Days)
Physician Decision
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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2
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5
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0
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1
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0
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0
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0
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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=99 Participants
|
28.0 Years
STANDARD_DEVIATION 16.49 • n=107 Participants
|
25.8 Years
STANDARD_DEVIATION 3.54 • n=206 Participants
|
26.3 Years
STANDARD_DEVIATION 4.46 • n=7 Participants
|
26.0 Years
STANDARD_DEVIATION 4.69 • n=31 Participants
|
26.7 Years
STANDARD_DEVIATION 5.65 • n=30 Participants
|
24.3 Years
STANDARD_DEVIATION 2.94 • n=3 Participants
|
28.0 Years
STANDARD_DEVIATION 7.04 • n=6 Participants
|
31.5 Years
STANDARD_DEVIATION 4.55 • n=114 Participants
|
—
|
26.3 Years
STANDARD_DEVIATION 4.76 • n=19 Participants
|
24.7 Years
STANDARD_DEVIATION 3.88 • n=4 Participants
|
35.3 Years
STANDARD_DEVIATION 12.75 • n=7 Participants
|
26.5 Years
STANDARD_DEVIATION 2.59 • n=7 Participants
|
31.2 Years
STANDARD_DEVIATION 11.51 • n=3 Participants
|
25.8 Years
STANDARD_DEVIATION 4.17 • n=4 Participants
|
—
|
—
|
—
|
27.1 Years
STANDARD_DEVIATION 7.18 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=114 Participants
|
—
|
0 Participants
n=19 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=4 Participants
|
—
|
—
|
—
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=31 Participants
|
6 Participants
n=30 Participants
|
6 Participants
n=3 Participants
|
6 Participants
n=6 Participants
|
6 Participants
n=114 Participants
|
—
|
6 Participants
n=19 Participants
|
6 Participants
n=4 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=3 Participants
|
6 Participants
n=4 Participants
|
—
|
—
|
—
|
104 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
3 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
2 Participants
n=6 Participants
|
2 Participants
n=114 Participants
|
—
|
2 Participants
n=19 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=3 Participants
|
1 Participants
n=4 Participants
|
—
|
—
|
—
|
12 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=114 Participants
|
—
|
0 Participants
n=19 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=4 Participants
|
—
|
—
|
—
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
15 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=31 Participants
|
5 Participants
n=30 Participants
|
5 Participants
n=3 Participants
|
4 Participants
n=6 Participants
|
4 Participants
n=114 Participants
|
—
|
3 Participants
n=19 Participants
|
4 Participants
n=4 Participants
|
6 Participants
n=7 Participants
|
6 Participants
n=7 Participants
|
5 Participants
n=3 Participants
|
4 Participants
n=4 Participants
|
—
|
—
|
—
|
79 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Brazilian
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
1 Participants
n=3 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=114 Participants
|
—
|
0 Participants
n=19 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=4 Participants
|
—
|
—
|
—
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Chinese/Australian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=114 Participants
|
—
|
0 Participants
n=19 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=4 Participants
|
—
|
—
|
—
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Egyptian/New Zealand
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=114 Participants
|
—
|
0 Participants
n=19 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=4 Participants
|
—
|
—
|
—
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Half White Half Italian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=114 Participants
|
—
|
0 Participants
n=19 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=4 Participants
|
—
|
—
|
—
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Indian
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=114 Participants
|
—
|
0 Participants
n=19 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=4 Participants
|
—
|
—
|
—
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Latin
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=114 Participants
|
—
|
1 Participants
n=19 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=4 Participants
|
—
|
—
|
—
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Moroccan
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
1 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=114 Participants
|
—
|
0 Participants
n=19 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=4 Participants
|
—
|
—
|
—
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Spanish/Jamaican/English/Irish
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=114 Participants
|
—
|
0 Participants
n=19 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=4 Participants
|
—
|
—
|
—
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Middle Eastern
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=114 Participants
|
—
|
0 Participants
n=19 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=3 Participants
|
0 Participants
n=4 Participants
|
—
|
—
|
—
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
South American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=114 Participants
|
—
|
0 Participants
n=19 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=3 Participants
|
1 Participants
n=4 Participants
|
—
|
—
|
—
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to Day 8Population: 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 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 2-Placebo
n=20 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 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
|
0 Participants
|
1 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to Day 8Population: 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 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 2-Placebo
n=20 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 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 4Population: 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 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 2-Placebo
n=20 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 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
|
3 Participants
|
2 Participants
|
4 Participants
|
3 Participants
|
3 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
3 Participants
|
—
|
1 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1Population: 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 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 2-Placebo
n=20 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 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
|
1 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 8Population: 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 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 2-Placebo
n=20 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 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
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
0 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: Up to Day 8Population: 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 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 2-Placebo
n=20 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 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
|
1 Participants
|
1 Participants
|
5 Participants
|
2 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 22Population: 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 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 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 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
|
3 Participants
|
4 Participants
|
2 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to Day 22Population: 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 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 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 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
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to Day 17Population: 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 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 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 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
|
0 Participants
|
2 Participants
|
1 Participants
|
1 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 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 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 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 22Population: 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 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 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 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
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to Day 22Population: 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 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 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 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
|
6 Participants
|
5 Participants
|
3 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 36Population: 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 36Population: 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 31Population: 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 36Population: 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 36Population: 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-dosePopulation: 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 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 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 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 t)
|
834.100 Hours*nanograms/milliliters
Geometric Coefficient of Variation 27.52
|
1951.059 Hours*nanograms/milliliters
Geometric Coefficient of Variation 14.25
|
184.934 Hours*nanograms/milliliters
Geometric Coefficient of Variation 21.32
|
307.945 Hours*nanograms/milliliters
Geometric Coefficient of Variation 17.76
|
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 inf)
|
840.806 Hours*nanograms/milliliters
Geometric Coefficient of Variation 27.54
|
1960.374 Hours*nanograms/milliliters
Geometric Coefficient of Variation 14.44
|
190.004 Hours*nanograms/milliliters
Geometric Coefficient of Variation 20.74
|
313.349 Hours*nanograms/milliliters
Geometric Coefficient of Variation 18.23
|
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 24)
|
840.740 Hours*nanograms/milliliters
Geometric Coefficient of Variation 27.54
|
1957.413 Hours*nanograms/milliliters
Geometric Coefficient of Variation 14.11
|
190.025 Hours*nanograms/milliliters
Geometric Coefficient of Variation 20.74
|
313.369 Hours*nanograms/milliliters
Geometric Coefficient of Variation 18.23
|
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-dosePopulation: PK Parameter Population.
Blood samples for PK analysis of GSK3008356 were collected at the indicated time points.
Outcome measures
| Measure |
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 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 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
|
458.496 Nanograms per milliliters
Geometric Coefficient of Variation 33.10
|
890.913 Nanograms per milliliters
Geometric Coefficient of Variation 15.87
|
92.417 Nanograms per milliliters
Geometric Coefficient of Variation 45.40
|
190.655 Nanograms per milliliters
Geometric Coefficient of Variation 22.40
|
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-dosePopulation: PK Parameter Population.
Blood samples for PK analysis of GSK3008356 were collected at the indicated time points.
Outcome measures
| Measure |
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 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 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
|
0.750 Hours
Standard Deviation 0.2739
|
0.756 Hours
Standard Deviation 0.2681
|
0.833 Hours
Standard Deviation 0.4082
|
0.542 Hours
Standard Deviation 0.2458
|
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
|
1.623 Hours
Standard Deviation 0.1928
|
2.113 Hours
Standard Deviation 1.2949
|
1.501 Hours
Standard Deviation 0.2048
|
1.425 Hours
Standard Deviation 0.1885
|
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 hoursPopulation: PK Parameter Population.
Urine samples for PK analysis of GSK3008356 were collected at the indicated time points.
Outcome measures
| Measure |
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 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 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
|
22.738 Nanograms*10^5
Standard Deviation 8.3640
|
62.332 Nanograms*10^5
Standard Deviation 4.6540
|
7.958 Nanograms*10^5
Standard Deviation 2.2225
|
8.699 Nanograms*10^5
Standard Deviation 2.3300
|
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 hoursPopulation: 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 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 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 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
|
2659.878 Milliliters per hour
Standard Deviation 645.2413
|
3214.711 Milliliters per hour
Standard Deviation 539.4800
|
4115.667 Milliliters per hour
Standard Deviation 855.3612
|
2752.580 Milliliters per hour
Standard Deviation 595.2028
|
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-dosePopulation: 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 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 2-Placebo
n=12 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)
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 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 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 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 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-dosePopulation: 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 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 2-Placebo
n=12 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)
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 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-dosePopulation: 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 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 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 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
|
0.800 Millimoles/Liters
Standard Deviation 0.2168
|
0.767 Millimoles/Liters
Standard Deviation 0.3817
|
0.925 Millimoles/Liters
Standard Deviation 0.2505
|
0.900 Millimoles/Liters
Standard Deviation 0.3178
|
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
|
0.700 Millimoles/Liters
Standard Deviation 0.2168
|
0.650 Millimoles/Liters
Standard Deviation 0.3317
|
0.825 Millimoles/Liters
Standard Deviation 0.2505
|
0.783 Millimoles/Liters
Standard Deviation 0.2733
|
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
|
0.717 Millimoles/Liters
Standard Deviation 0.2503
|
0.667 Millimoles/Liters
Standard Deviation 0.2893
|
0.825 Millimoles/Liters
Standard Deviation 0.2545
|
0.817 Millimoles/Liters
Standard Deviation 0.2338
|
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
|
0.783 Millimoles/Liters
Standard Deviation 0.2805
|
0.617 Millimoles/Liters
Standard Deviation 0.2696
|
1.058 Millimoles/Liters
Standard Deviation 0.3056
|
0.733 Millimoles/Liters
Standard Deviation 0.2273
|
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
|
0.950 Millimoles/Liters
Standard Deviation 0.2864
|
0.767 Millimoles/Liters
Standard Deviation 0.3281
|
1.308 Millimoles/Liters
Standard Deviation 0.4092
|
0.867 Millimoles/Liters
Standard Deviation 0.2714
|
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
|
1.017 Millimoles/Liters
Standard Deviation 0.3502
|
0.817 Millimoles/Liters
Standard Deviation 0.2582
|
1.425 Millimoles/Liters
Standard Deviation 0.4612
|
0.983 Millimoles/Liters
Standard Deviation 0.3531
|
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
|
0.950 Millimoles/Liters
Standard Deviation 0.3493
|
0.850 Millimoles/Liters
Standard Deviation 0.2608
|
1.275 Millimoles/Liters
Standard Deviation 0.4783
|
0.967 Millimoles/Liters
Standard Deviation 0.3601
|
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
|
0.850 Millimoles/Liters
Standard Deviation 0.3464
|
0.850 Millimoles/Liters
Standard Deviation 0.2000
|
1.158 Millimoles/Liters
Standard Deviation 0.4018
|
0.833 Millimoles/Liters
Standard Deviation 0.3093
|
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
|
0.733 Millimoles/Liters
Standard Deviation 0.3573
|
0.767 Millimoles/Liters
Standard Deviation 0.1722
|
1.008 Millimoles/Liters
Standard Deviation 0.4042
|
0.750 Millimoles/Liters
Standard Deviation 0.2683
|
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
|
0.700 Millimoles/Liters
Standard Deviation 0.3178
|
0.667 Millimoles/Liters
Standard Deviation 0.2090
|
0.725 Millimoles/Liters
Standard Deviation 0.2697
|
0.583 Millimoles/Liters
Standard Deviation 0.1693
|
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 dosePopulation: 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 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)
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 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 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
|
107.191 Hours*nanograms/milliliters
Geometric Coefficient of Variation 32.12
|
—
|
279.222 Hours*nanograms/milliliters
Geometric Coefficient of Variation 26.39
|
31.959 Hours*nanograms/milliliters
Geometric Coefficient of Variation 25.16
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
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
|
101.151 Hours*nanograms/milliliters
Geometric Coefficient of Variation 20.20
|
—
|
—
|
37.429 Hours*nanograms/milliliters
Geometric Coefficient of Variation 21.97
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
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 dosePopulation: 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 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)
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 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 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 14
|
46.736 Nanograms/milliliters
Geometric Coefficient of Variation 17.52
|
—
|
—
|
16.424 Nanograms/milliliters
Geometric Coefficient of Variation 33.86
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Cmax of GSK3008356 on Day 1 and Day 14
Day 1
|
77.326 Nanograms/milliliters
Geometric Coefficient of Variation 31.73
|
—
|
187.032 Nanograms/milliliters
Geometric Coefficient of Variation 28.69
|
17.638 Nanograms/milliliters
Geometric Coefficient of Variation 40.02
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
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 dosePopulation: 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 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)
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 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 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
t1/2 on Day 1
|
1.443 Hours
Standard Deviation 0.1624
|
—
|
1.319 Hours
Standard Deviation 0.1512
|
1.312 Hours
Standard Deviation 0.1369
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: t1/2 and Tmax of GSK3008356 on Day 1 and Day 14
t1/2 on Day 14
|
2.115 Hours
Standard Deviation 1.3252
|
—
|
—
|
1.406 Hours
Standard Deviation 0.2138
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: t1/2 and Tmax of GSK3008356 on Day 1 and Day 14
Tmax on Day 1
|
0.436 Hours
Standard Deviation 0.1511
|
—
|
0.517 Hours
Standard Deviation 0.0279
|
0.583 Hours
Standard Deviation 0.2041
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: t1/2 and Tmax of GSK3008356 on Day 1 and Day 14
Tmax on Day 14
|
0.550 Hours
Standard Deviation 0.2739
|
—
|
—
|
0.875 Hours
Standard Deviation 0.6275
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 24 hours post-dose on Day 14Population: 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 14Population: 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 dosePopulation: 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 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 2-Placebo
n=12 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)
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 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
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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|
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
|
—
|
—
|
—
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—
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—
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—
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—
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—
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—
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|
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
|
—
|
—
|
—
|
—
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—
|
—
|
—
|
—
|
—
|
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-dosePopulation: 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 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 2-Placebo
n=12 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)
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 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 dosePopulation: 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 2-Cohort B2: GSK3008356 1 mg BID (0 h, 16 h)
n=5 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)
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 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)
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 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
|
1.010 Ratio
Geometric Coefficient of Variation 19.76
|
—
|
—
|
1.171 Ratio
Geometric Coefficient of Variation 13.52
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Observed Accumulation Ratio of GSK3008356
Rcmax
|
0.606 Ratio
Geometric Coefficient of Variation 38.82
|
—
|
—
|
0.931 Ratio
Geometric Coefficient of Variation 22.64
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose on Days 2, 4, 5, 6, 12, 13, 14 and the 24 hours post-dose on Day 14Population: 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 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)
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 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 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
|
4.025 Nanograms/Milliliters
Standard Deviation 1.7353
|
—
|
11.953 Nanograms/Milliliters
Standard Deviation 7.8239
|
2.595 Nanograms/Milliliters
Standard Deviation 2.0718
|
—
|
—
|
—
|
—
|
—
|
—
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—
|
—
|
|
Part 2: Trough Plasma Concentrations (Ctrough) to Assess Steady State of GSK3008356 Following 14-day Repeat Dosing
Day 4, Pre-Dose
|
1.940 Nanograms/Milliliters
Standard Deviation 2.2364
|
—
|
11.528 Nanograms/Milliliters
Standard Deviation 7.2515
|
1.362 Nanograms/Milliliters
Standard Deviation 0.7706
|
—
|
—
|
—
|
—
|
—
|
—
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—
|
—
|
|
Part 2: Trough Plasma Concentrations (Ctrough) to Assess Steady State of GSK3008356 Following 14-day Repeat Dosing
Day 5, Pre-Dose
|
6.595 Nanograms/Milliliters
Standard Deviation 4.8009
|
—
|
4.790 Nanograms/Milliliters
Standard Deviation 2.2425
|
1.392 Nanograms/Milliliters
Standard Deviation 1.6697
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Trough Plasma Concentrations (Ctrough) to Assess Steady State of GSK3008356 Following 14-day Repeat Dosing
Day 6, Pre-Dose
|
3.206 Nanograms/Milliliters
Standard Deviation 1.9157
|
—
|
2.880 Nanograms/Milliliters
Standard Deviation 2.6985
|
0.475 Nanograms/Milliliters
Standard Deviation 0.7364
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Trough Plasma Concentrations (Ctrough) to Assess Steady State of GSK3008356 Following 14-day Repeat Dosing
Day 12, Pre-Dose
|
1.934 Nanograms/Milliliters
Standard Deviation 1.0154
|
—
|
—
|
0.205 Nanograms/Milliliters
Standard Deviation 0.5021
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Trough Plasma Concentrations (Ctrough) to Assess Steady State of GSK3008356 Following 14-day Repeat Dosing
Day 13, Pre-Dose
|
3.756 Nanograms/Milliliters
Standard Deviation 2.1434
|
—
|
—
|
0.325 Nanograms/Milliliters
Standard Deviation 0.7961
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Trough Plasma Concentrations (Ctrough) to Assess Steady State of GSK3008356 Following 14-day Repeat Dosing
Day 14, Pre-Dose
|
4.368 Nanograms/Milliliters
Standard Deviation 3.3806
|
—
|
—
|
1.587 Nanograms/Milliliters
Standard Deviation 1.3835
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Trough Plasma Concentrations (Ctrough) to Assess Steady State of GSK3008356 Following 14-day Repeat Dosing
Day 14, 24 Hour
|
1.866 Nanograms/Milliliters
Standard Deviation 0.4191
|
—
|
—
|
1.420 Nanograms/Milliliters
Standard Deviation 0.6255
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
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 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)
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 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 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 1, 1 hour post-dose
|
1.217 Millimoles/Liter
Standard Deviation 0.3697
|
—
|
0.867 Millimoles/Liter
Standard Deviation 0.4987
|
0.950 Millimoles/Liter
Standard Deviation 0.3017
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356
Day 1, 2 hour post-dose
|
0.950 Millimoles/Liter
Standard Deviation 0.2236
|
—
|
0.800 Millimoles/Liter
Standard Deviation 0.4219
|
0.783 Millimoles/Liter
Standard Deviation 0.2317
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356
Day 1, 3 hour post-dose
|
0.983 Millimoles/Liter
Standard Deviation 0.2503
|
—
|
0.767 Millimoles/Liter
Standard Deviation 0.4987
|
0.883 Millimoles/Liter
Standard Deviation 0.3189
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356
Day 1, 4 hour post-dose
|
1.067 Millimoles/Liter
Standard Deviation 0.3220
|
—
|
0.883 Millimoles/Liter
Standard Deviation 0.4956
|
0.833 Millimoles/Liter
Standard Deviation 0.3235
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356
Day 1, 5 hour post-dose
|
1.317 Millimoles/Liter
Standard Deviation 0.4655
|
—
|
1.033 Millimoles/Liter
Standard Deviation 0.4633
|
1.017 Millimoles/Liter
Standard Deviation 0.4309
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356
Day 1, 6 hour post-dose
|
1.500 Millimoles/Liter
Standard Deviation 0.5523
|
—
|
1.150 Millimoles/Liter
Standard Deviation 0.4990
|
1.050 Millimoles/Liter
Standard Deviation 0.6189
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356
Day 1, 7 hour post-dose
|
1.700 Millimoles/Liter
Standard Deviation 0.3987
|
—
|
1.300 Millimoles/Liter
Standard Deviation 0.5933
|
1.233 Millimoles/Liter
Standard Deviation 0.7005
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356
Day 1, 8 hour post-dose
|
1.717 Millimoles/Liter
Standard Deviation 0.4676
|
—
|
1.283 Millimoles/Liter
Standard Deviation 0.7561
|
1.167 Millimoles/Liter
Standard Deviation 0.6578
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356
Day 1, 9 hour post-dose
|
1.467 Millimoles/Liter
Standard Deviation 0.5037
|
—
|
1.050 Millimoles/Liter
Standard Deviation 0.6442
|
1.000 Millimoles/Liter
Standard Deviation 0.6293
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356
Day 1, 12 hour post-dose
|
1.033 Millimoles/Liter
Standard Deviation 0.2041
|
—
|
0.800 Millimoles/Liter
Standard Deviation 0.4359
|
0.717 Millimoles/Liter
Standard Deviation 0.3996
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356
Day 14, 1 hour post-dose
|
1.020 Millimoles/Liter
Standard Deviation 0.2490
|
—
|
—
|
0.917 Millimoles/Liter
Standard Deviation 0.3077
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356
Day 14, 2 hour post-dose
|
0.960 Millimoles/Liter
Standard Deviation 0.1597
|
—
|
—
|
0.817 Millimoles/Liter
Standard Deviation 0.2582
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356
Day 14, 3 hour post-dose
|
1.080 Millimoles/Liter
Standard Deviation 0.1924
|
—
|
—
|
0.950 Millimoles/Liter
Standard Deviation 0.2757
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356
Day 14, 4 hour post-dose
|
1.020 Millimoles/Liter
Standard Deviation 0.2907
|
—
|
—
|
1.017 Millimoles/Liter
Standard Deviation 0.2840
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356
Day 14, 5 hour post-dose
|
1.060 Millimoles/Liter
Standard Deviation 0.2748
|
—
|
—
|
1.100 Millimoles/Liter
Standard Deviation 0.3860
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356
Day 14, 6 hour post-dose
|
1.260 Millimoles/Liter
Standard Deviation 0.3943
|
—
|
—
|
1.217 Millimoles/Liter
Standard Deviation 0.5066
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356
Day 14, 7 hour post-dose
|
1.460 Millimoles/Liter
Standard Deviation 0.2608
|
—
|
—
|
1.367 Millimoles/Liter
Standard Deviation 0.5345
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356
Day 14, 8 hour post-dose
|
1.380 Millimoles/Liter
Standard Deviation 0.4764
|
—
|
—
|
1.367 Millimoles/Liter
Standard Deviation 0.4834
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356
Day 14, 9 hour post-dose
|
1.220 Millimoles/Liter
Standard Deviation 0.5239
|
—
|
—
|
0.817 Millimoles/Liter
Standard Deviation 0.4844
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Part 2: Postprandial Triglyceride Levels Following 14-day Repeat Dosing of GSK3008356
Day 14, 12 hour post-dose
|
0.720 Millimoles/Liter
Standard Deviation 0.6079
|
—
|
—
|
0.800 Millimoles/Liter
Standard Deviation 0.4889
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
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 28Population: 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 28Population: 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 28Population: 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 28Population: 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 cohortPopulation: 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 cohortPopulation: 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 28Population: 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 28Population: 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 28Population: 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 3Population: 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- 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 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-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- 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 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-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
|
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.
|
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%
0/6 • 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
|
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.
|
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%
0/6 • 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
|
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.
|
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%
0/6 • 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%
0/20 • 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.
|
—
0/0 • 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%
0/6 • 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
|
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.
|
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%
0/6 • 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
|
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.
|
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%
0/6 • 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
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