Trial Outcomes & Findings for Phase I Study of GSK2982772 in Japanese Healthy Male Participants (NCT NCT03590613)
NCT ID: NCT03590613
Last Updated: 2023-10-04
Results Overview
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. Safety population comprised of all participants who have received at least one dose of study treatment. This population was used for the safety analyses.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
13 participants
Primary outcome timeframe
From the day of first dose to 39 days
Results posted on
2023-10-04
Participant Flow
This was a 4-way crossover, single-center, randomized, double-blind, dose-ascending, placebo (PBO)-controlled study to evaluate the safety, tolerability, and pharmacokinetics of oral TID doses (thrice a day) of GSK2982772 in healthy male Japanese participants
A total of 13 healthy male Japanese participants were enrolled in the study to receive GSK2982772 and PBO from a single center in Japan
Participant milestones
| Measure |
Treatment Sequence A: PBO TID /60mg TID /120mg TID /240mg TID
Participants in this arm received PBO TID in treatment period (TP) 1, GSK2982772 60 milligram (mg) TID in TP2, GSK2982772 120 mg TID in TP3 and GSK2982772 240 mg TID in TP4. GSK2982772 and placebo was administered at 0 hour (starting dose), 7 hours (second dose) and 14 hours (third dose) on Day 1 in each TP. Participants had fasted overnight for 8 hours before first dose. Each TP was followed by a washout period of at least 7 days, for each participant.
|
Treatment Sequence B: 60mg TID /PBO TID /120mg TID /240mg TID
Participants in this arm received GSK2982772 60 mg TID in TP1, PBO TID in TP2, GSK2982772 120mg TID in TP3 and GSK2982772 240 mg TID in TP4. GSK2982772 and placebo was administered at 0 hour (starting dose), 7 hours (second dose) and 14 hours (third dose) on Day 1 in each TP. Participants had fasted overnight for 8 hours before first dose. Each TP was followed by a washout period of at least 7 days, for each participant.
|
Treatment Sequence C: 60mg TID/ 120mg TID/ PBO TID/ 240mg TID
Participants in this arm received GSK2982772 60 mg TID in TP1, GSK2982772 120mg TID in TP2, PBO TID in TP3 and GSK2982772 240 mg TID in TP4. GSK2982772 and placebo was administered at 0 hour (starting dose), 7 hours (second dose) and 14 hours (third dose) on Day 1 in each TP. Participants had fasted overnight for 8 hours before first dose. Each TP was followed by a washout period of at least 7 days, for each participant.
|
Treatment Sequence D: 60mg TID /120mg TID /240mg TID /PBO TID
Participants in this arm received GSK2982772 60 mg TID in TP1, GSK2982772 120mg TID in TP2, GSK2982772 240 mg TID in TP3 and PBO TID in TP4. GSK2982772 and placebo was administered at 0 hour (starting dose), 7 hours (second dose) and 14 hours (third dose) on Day 1 in each TP. Participants had fasted overnight for 8 hours before first dose. Each TP was followed by a washout period of at least 7 days, for each participant.
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|---|---|---|---|---|
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Period 1, 4 Days
STARTED
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3
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3
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3
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3
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Period 1, 4 Days
COMPLETED
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3
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3
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3
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3
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Period 1, 4 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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Period 1, Wash-out, at Least 3 Days
STARTED
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3
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3
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3
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3
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Period 1, Wash-out, at Least 3 Days
COMPLETED
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3
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3
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3
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3
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Period 1, Wash-out, at Least 3 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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Period 2, 4 Days
STARTED
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3
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3
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3
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4
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Period 2, 4 Days
COMPLETED
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3
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3
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3
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3
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Period 2, 4 Days
NOT COMPLETED
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0
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0
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0
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1
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Period 2, Wash-out, at Least 3 Days
STARTED
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3
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3
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3
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3
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Period 2, Wash-out, at Least 3 Days
COMPLETED
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3
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3
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3
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3
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Period 2, Wash-out, at Least 3 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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Period 3, 4 Days
STARTED
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3
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3
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3
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3
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Period 3, 4 Days
COMPLETED
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3
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3
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3
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3
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Period 3, 4 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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Period 3,Wash-out, at Least 3 Days
STARTED
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3
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3
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3
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3
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Period 3,Wash-out, at Least 3 Days
COMPLETED
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3
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3
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3
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3
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Period 3,Wash-out, at Least 3 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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Period 4, 4 Days
STARTED
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3
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3
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3
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3
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Period 4, 4 Days
COMPLETED
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3
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3
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3
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3
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Period 4, 4 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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Reasons for withdrawal
| Measure |
Treatment Sequence A: PBO TID /60mg TID /120mg TID /240mg TID
Participants in this arm received PBO TID in treatment period (TP) 1, GSK2982772 60 milligram (mg) TID in TP2, GSK2982772 120 mg TID in TP3 and GSK2982772 240 mg TID in TP4. GSK2982772 and placebo was administered at 0 hour (starting dose), 7 hours (second dose) and 14 hours (third dose) on Day 1 in each TP. Participants had fasted overnight for 8 hours before first dose. Each TP was followed by a washout period of at least 7 days, for each participant.
|
Treatment Sequence B: 60mg TID /PBO TID /120mg TID /240mg TID
Participants in this arm received GSK2982772 60 mg TID in TP1, PBO TID in TP2, GSK2982772 120mg TID in TP3 and GSK2982772 240 mg TID in TP4. GSK2982772 and placebo was administered at 0 hour (starting dose), 7 hours (second dose) and 14 hours (third dose) on Day 1 in each TP. Participants had fasted overnight for 8 hours before first dose. Each TP was followed by a washout period of at least 7 days, for each participant.
|
Treatment Sequence C: 60mg TID/ 120mg TID/ PBO TID/ 240mg TID
Participants in this arm received GSK2982772 60 mg TID in TP1, GSK2982772 120mg TID in TP2, PBO TID in TP3 and GSK2982772 240 mg TID in TP4. GSK2982772 and placebo was administered at 0 hour (starting dose), 7 hours (second dose) and 14 hours (third dose) on Day 1 in each TP. Participants had fasted overnight for 8 hours before first dose. Each TP was followed by a washout period of at least 7 days, for each participant.
|
Treatment Sequence D: 60mg TID /120mg TID /240mg TID /PBO TID
Participants in this arm received GSK2982772 60 mg TID in TP1, GSK2982772 120mg TID in TP2, GSK2982772 240 mg TID in TP3 and PBO TID in TP4. GSK2982772 and placebo was administered at 0 hour (starting dose), 7 hours (second dose) and 14 hours (third dose) on Day 1 in each TP. Participants had fasted overnight for 8 hours before first dose. Each TP was followed by a washout period of at least 7 days, for each participant.
|
|---|---|---|---|---|
|
Period 2, 4 Days
Physician Decision
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Phase I Study of GSK2982772 in Japanese Healthy Male Participants
Baseline characteristics by cohort
| Measure |
All Study Participants
n=13 Participants
All study participants received GSK2982772 and PBO in four treatment sequences (A,B,C \&D) at 0 hour (starting dose), 7 hours (second dose) and 14 hours (third dose) on Day 1 in each TP.
|
|---|---|
|
Age, Continuous
|
26.2 Years
STANDARD_DEVIATION 7.34 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian-Japanese/East Asian/South East AsianHeritage
|
13 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From the day of first dose to 39 daysPopulation: Safety Population.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, associated with liver injury and impaired liver function or any other situations as per medical or scientific judgement. Safety population comprised of all participants who have received at least one dose of study treatment. This population was used for the safety analyses.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any AE
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Reporting Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any SAE
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 72 hours at each treatment periodPopulation: Safety Population.
Blood samples were collected for the analysis of clinical chemistry parameters including: glucose, calcium, cholesterol, chloride, high density lipoprotein (HDL) cholesterol, potassium, low density lipoprotein (LDL) cholesterol, phosphate, sodium, triglycerides and urea. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Clinical Chemistry Parameters
Glucose
|
-0.240543 Millimoles per liter
Standard Deviation 0.1426732
|
-0.282176 Millimoles per liter
Standard Deviation 0.2348638
|
-0.240543 Millimoles per liter
Standard Deviation 0.2902134
|
-0.226666 Millimoles per liter
Standard Deviation 0.2554319
|
|
Change From Baseline in Clinical Chemistry Parameters
Calcium
|
0.016633 Millimoles per liter
Standard Deviation 0.0683974
|
0.058217 Millimoles per liter
Standard Deviation 0.0341987
|
-0.022871 Millimoles per liter
Standard Deviation 0.0732901
|
-0.004158 Millimoles per liter
Standard Deviation 0.1036024
|
|
Change From Baseline in Clinical Chemistry Parameters
Cholesterol
|
0.000000 Millimoles per liter
Standard Deviation 0.2092177
|
0.073270 Millimoles per liter
Standard Deviation 0.2657498
|
0.015085 Millimoles per liter
Standard Deviation 0.3458001
|
-0.049565 Millimoles per liter
Standard Deviation 0.3560217
|
|
Change From Baseline in Clinical Chemistry Parameters
Chloride
|
1.1 Millimoles per liter
Standard Deviation 1.38
|
0.2 Millimoles per liter
Standard Deviation 2.25
|
1.2 Millimoles per liter
Standard Deviation 1.59
|
0.6 Millimoles per liter
Standard Deviation 1.68
|
|
Change From Baseline in Clinical Chemistry Parameters
HDL Cholesterol
|
-0.071115 Millimoles per liter
Standard Deviation 0.1097839
|
-0.034480 Millimoles per liter
Standard Deviation 0.1070976
|
-0.084045 Millimoles per liter
Standard Deviation 0.1046815
|
-0.116370 Millimoles per liter
Standard Deviation 0.0578247
|
|
Change From Baseline in Clinical Chemistry Parameters
Potassium
|
-0.06 Millimoles per liter
Standard Deviation 0.156
|
0.01 Millimoles per liter
Standard Deviation 0.329
|
0.03 Millimoles per liter
Standard Deviation 0.501
|
-0.07 Millimoles per liter
Standard Deviation 0.419
|
|
Change From Baseline in Clinical Chemistry Parameters
LDL Cholesterol
|
0.036635 Millimoles per liter
Standard Deviation 0.1670318
|
0.101285 Millimoles per liter
Standard Deviation 0.1673953
|
0.017240 Millimoles per liter
Standard Deviation 0.2663211
|
-0.043100 Millimoles per liter
Standard Deviation 0.1926790
|
|
Change From Baseline in Clinical Chemistry Parameters
Phosphate
|
0.064580 Millimoles per liter
Standard Deviation 0.0963795
|
0.053817 Millimoles per liter
Standard Deviation 0.1210793
|
0.002691 Millimoles per liter
Standard Deviation 0.1155721
|
0.018836 Millimoles per liter
Standard Deviation 0.1366196
|
|
Change From Baseline in Clinical Chemistry Parameters
Sodium
|
1.5 Millimoles per liter
Standard Deviation 1.78
|
1.3 Millimoles per liter
Standard Deviation 1.72
|
0.9 Millimoles per liter
Standard Deviation 1.93
|
1.4 Millimoles per liter
Standard Deviation 1.83
|
|
Change From Baseline in Clinical Chemistry Parameters
Triglycerides
|
0.19398 Millimoles per liter
Standard Deviation 0.117614
|
0.12618 Millimoles per liter
Standard Deviation 0.153495
|
0.13372 Millimoles per liter
Standard Deviation 0.286674
|
0.13466 Millimoles per liter
Standard Deviation 0.368074
|
|
Change From Baseline in Clinical Chemistry Parameters
Urea
|
-0.09223 Millimoles per liter
Standard Deviation 0.656241
|
-0.21123 Millimoles per liter
Standard Deviation 0.796454
|
-0.03273 Millimoles per liter
Standard Deviation 0.309530
|
-0.31238 Millimoles per liter
Standard Deviation 0.705860
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 72 hours at each Treatment PeriodPopulation: Safety Population.
Blood samples were collected for the analysis of clinical chemistry parameters including: albumin and protein. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein
Albumin
|
-1.4 Grams per liter
Standard Deviation 2.64
|
-0.4 Grams per liter
Standard Deviation 1.62
|
-1.6 Grams per liter
Standard Deviation 2.47
|
-2.5 Grams per liter
Standard Deviation 3.23
|
|
Change From Baseline in Clinical Chemistry Parameters: Albumin and Protein
Protein
|
-1.3 Grams per liter
Standard Deviation 3.96
|
0.8 Grams per liter
Standard Deviation 2.12
|
-2.1 Grams per liter
Standard Deviation 3.70
|
-2.3 Grams per liter
Standard Deviation 4.27
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 72 hours at each Treatment PeriodPopulation: Safety Population.
Blood samples were collected for the analysis of clinical chemistry parameters including: ALP, ALT, AST, CK, GGT and LDH. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH)
ALP
|
-9.1 International units per liter
Standard Deviation 17.32
|
-6.8 International units per liter
Standard Deviation 12.63
|
-10.6 International units per liter
Standard Deviation 14.41
|
-9.0 International units per liter
Standard Deviation 14.65
|
|
Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH)
ALT
|
-0.5 International units per liter
Standard Deviation 3.66
|
0.5 International units per liter
Standard Deviation 2.47
|
-2.2 International units per liter
Standard Deviation 3.33
|
-1.3 International units per liter
Standard Deviation 4.59
|
|
Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH)
AST
|
-0.6 International units per liter
Standard Deviation 2.68
|
0.3 International units per liter
Standard Deviation 1.76
|
-1.8 International units per liter
Standard Deviation 3.28
|
-2.5 International units per liter
Standard Deviation 6.64
|
|
Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH)
CK
|
-19.1 International units per liter
Standard Deviation 14.95
|
-34.2 International units per liter
Standard Deviation 21.70
|
-51.7 International units per liter
Standard Deviation 48.61
|
-39.6 International units per liter
Standard Deviation 32.91
|
|
Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH)
GGT
|
-0.5 International units per liter
Standard Deviation 0.67
|
-0.5 International units per liter
Standard Deviation 1.62
|
-1.8 International units per liter
Standard Deviation 2.93
|
-1.5 International units per liter
Standard Deviation 2.32
|
|
Change From Baseline in Clinical Chemistry Parameters: Alkaline Phosphate (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatinine Kinase (CK), Gamma Glutamyl Transferase (GGT) and Lactate Dehydrognase (LDH)
LDH
|
-17.7 International units per liter
Standard Deviation 9.76
|
-11.3 International units per liter
Standard Deviation 8.01
|
-21.6 International units per liter
Standard Deviation 14.92
|
-21.3 International units per liter
Standard Deviation 10.34
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 72 hours at each Treatment PeriodPopulation: Safety Population
Blood samples were collected for the analysis of clinical chemistry parameter: amylase. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Clinical Chemistry Parameter: Amylase
|
4.2 Units per liter
Standard Deviation 10.56
|
9.1 Units per liter
Standard Deviation 6.26
|
4.4 Units per liter
Standard Deviation 9.34
|
1.1 Units per liter
Standard Deviation 8.40
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 72 hours at each Treatment PeriodPopulation: Safety Population.
Blood samples were collected for the analysis of clinical chemistry parameters:direct bilirubin, bilirubin, creatinine and urate. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid)
Direct bilirubin
|
0.428 Micromoles per liter
Standard Deviation 1.0629
|
0.285 Micromoles per liter
Standard Deviation 0.9873
|
0.143 Micromoles per liter
Standard Deviation 1.1432
|
-0.285 Micromoles per liter
Standard Deviation 0.9873
|
|
Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid)
Bilirubin
|
2.850 Micromoles per liter
Standard Deviation 4.7998
|
2.850 Micromoles per liter
Standard Deviation 4.7998
|
1.568 Micromoles per liter
Standard Deviation 5.9441
|
-0.428 Micromoles per liter
Standard Deviation 4.0679
|
|
Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid)
Creatinine
|
0.8840 Micromoles per liter
Standard Deviation 7.47252
|
0.5157 Micromoles per liter
Standard Deviation 4.46730
|
0.6630 Micromoles per liter
Standard Deviation 5.25184
|
1.6943 Micromoles per liter
Standard Deviation 3.97949
|
|
Change From Baseline in Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine and Urate (Uric Acid)
Urate
|
21.8093 Micromoles per liter
Standard Deviation 29.82999
|
9.4177 Micromoles per liter
Standard Deviation 23.16992
|
17.8440 Micromoles per liter
Standard Deviation 17.93389
|
8.4263 Micromoles per liter
Standard Deviation 27.95138
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 72 hours at each Treatment PeriodPopulation: Safety Population.
Blood samples were collected for the analysis of clinical chemistry parameter: CRP. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Clinical Chemistry Parameter: C-reactive Protein (CRP) of TID Doses for One Day of GSK2982772
|
-0.078 Milligrams per liter
Standard Deviation 0.2290
|
-0.016 Milligrams per liter
Standard Deviation 0.0268
|
-0.050 Milligrams per liter
Standard Deviation 0.1028
|
0.126 Milligrams per liter
Standard Deviation 0.5390
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 72 hours at each Treatment PeriodPopulation: Safety Population.
Blood samples were collected for the analysis of hematology parameter: hematocrit. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Hematology Parameter: Hematocrit
|
0.0039 Percentage of red blood cells in blood
Standard Deviation 0.01946
|
0.0075 Percentage of red blood cells in blood
Standard Deviation 0.01332
|
-0.0048 Percentage of red blood cells in blood
Standard Deviation 0.01434
|
-0.0043 Percentage of red blood cells in blood
Standard Deviation 0.02172
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 72 hours at each Treatment PeriodPopulation: Safety Population.
Blood samples were collected for the analysis of hematology parameter: hemoglobin. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Hematology Parameter: Hemoglobin
|
2.4 Grams per liter
Standard Deviation 6.01
|
4.6 Grams per liter
Standard Deviation 5.74
|
-1.4 Grams per liter
Standard Deviation 5.57
|
-0.4 Grams per liter
Standard Deviation 8.65
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 72 hours at each Treatment PeriodPopulation: Safety Population.
Blood samples were collected for the analysis of hematology parameter: erythrocyte MCH. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Hemoglobin (MCH)
|
0.12 Picograms
Standard Deviation 0.269
|
0.17 Picograms
Standard Deviation 0.299
|
0.10 Picograms
Standard Deviation 0.234
|
0.15 Picograms
Standard Deviation 0.261
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 72 hours at each Treatment PeriodPopulation: Safety Population.
Blood samples were collected for the analysis of hematology parameter: erythrocyte MCV. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Hematology Parameter: Erythrocyte Mean Corpuscular Volume (MCV)
|
-0.4 Femtoliters
Standard Deviation 0.90
|
-0.7 Femtoliters
Standard Deviation 0.89
|
-0.2 Femtoliters
Standard Deviation 0.39
|
-0.4 Femtoliters
Standard Deviation 0.90
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 72 hours at each Treatment PeriodPopulation: Safety Population.
Blood samples were collected for the analysis of hematology parameter: erythrocytes. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Hematology Parameter: Erythrocytes
|
0.058 10^12 cells per liter
Standard Deviation 0.2387
|
0.126 10^12 cells per liter
Standard Deviation 0.1583
|
-0.059 10^12 cells per liter
Standard Deviation 0.1624
|
-0.035 10^12 cells per liter
Standard Deviation 0.2731
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 72 hours at each Treatment PeriodPopulation: Safety Population.
Blood samples were collected for the analysis of hematology parameter: percentage reticulocytes. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Hematology Parameter: Reticulocytes/Erythrocytes
|
0.0002 Ratio of Reticulocytes to Erythrocytes
Standard Deviation 0.00221
|
0.0001 Ratio of Reticulocytes to Erythrocytes
Standard Deviation 0.00188
|
-0.0008 Ratio of Reticulocytes to Erythrocytes
Standard Deviation 0.00242
|
-0.0003 Ratio of Reticulocytes to Erythrocytes
Standard Deviation 0.00201
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 72 hours at each Treatment PeriodPopulation: Safety Population.
Blood samples were collected for the analysis of hematology parameters including platelet count and leukocytes. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Hematology Parameters: Platelets and Leukocytes of TID Doses for One Day of GSK2982772
Platelets
|
-1.8 10^9 cells per liter
Standard Deviation 21.35
|
2.5 10^9 cells per liter
Standard Deviation 26.12
|
-12.8 10^9 cells per liter
Standard Deviation 23.03
|
-6.4 10^9 cells per liter
Standard Deviation 18.59
|
|
Change From Baseline in Hematology Parameters: Platelets and Leukocytes of TID Doses for One Day of GSK2982772
Leukocytes
|
-0.43 10^9 cells per liter
Standard Deviation 0.927
|
-0.05 10^9 cells per liter
Standard Deviation 0.992
|
-0.42 10^9 cells per liter
Standard Deviation 1.214
|
-0.62 10^9 cells per liter
Standard Deviation 0.860
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 72 hours at each Treatment PeriodPopulation: Safety Population.
Blood samples were collected for the analysis of hematology parameters including neutrophils/leukocytes, lymphocytes/leukocytes, monocytes/leukocytes, eosinophils/leukocytes and basophils/leukocytes. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772
Lymphocytes/Leukocytes
|
1.29 Percentage of cells in leukocytes
Standard Deviation 4.206
|
1.02 Percentage of cells in leukocytes
Standard Deviation 4.329
|
1.49 Percentage of cells in leukocytes
Standard Deviation 4.847
|
2.29 Percentage of cells in leukocytes
Standard Deviation 8.349
|
|
Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772
Eosinophils/Leukocytes
|
-0.18 Percentage of cells in leukocytes
Standard Deviation 0.666
|
-0.22 Percentage of cells in leukocytes
Standard Deviation 1.335
|
-0.66 Percentage of cells in leukocytes
Standard Deviation 1.377
|
-0.27 Percentage of cells in leukocytes
Standard Deviation 0.537
|
|
Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772
Basophils/Leukocytes
|
-0.02 Percentage of cells in leukocytes
Standard Deviation 0.180
|
-0.01 Percentage of cells in leukocytes
Standard Deviation 0.090
|
-0.08 Percentage of cells in leukocytes
Standard Deviation 0.129
|
0.02 Percentage of cells in leukocytes
Standard Deviation 0.134
|
|
Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772
Monocytes/Leukocytes
|
-1.13 Percentage of cells in leukocytes
Standard Deviation 1.598
|
-0.24 Percentage of cells in leukocytes
Standard Deviation 1.019
|
-0.01 Percentage of cells in leukocytes
Standard Deviation 1.176
|
-0.48 Percentage of cells in leukocytes
Standard Deviation 1.532
|
|
Change From Baseline in Hematology Parameters of TID Doses for One Day of GSK2982772
Neutrophils/Leukocytes
|
0.04 Percentage of cells in leukocytes
Standard Deviation 4.656
|
-0.55 Percentage of cells in leukocytes
Standard Deviation 4.356
|
-0.75 Percentage of cells in leukocytes
Standard Deviation 5.841
|
-1.57 Percentage of cells in leukocytes
Standard Deviation 8.363
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 72 hours at each Treatment PeriodPopulation: Safety Population.
Urine samples were collected for analysis of urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH of less than 7 is acidic and a pH of greater than 7 is basic. Normal urine has a slightly acidic pH (5.0-6.0). Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Urine Potential of Hydrogen (pH)
|
0.13 pH
Standard Deviation 0.569
|
0.42 pH
Standard Deviation 0.515
|
0.42 pH
Standard Deviation 0.515
|
-0.17 pH
Standard Deviation 0.537
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 72 hours at each Treatment PeriodPopulation: Safety Population.
Urine samples were collected for analysis of urine specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. The urinary specific gravity measurement is a routine part of urinalysis. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Urine Specific Gravity
|
0.0093 Ratio of urine density to water density
Standard Deviation 0.00702
|
0.0042 Ratio of urine density to water density
Standard Deviation 0.00780
|
0.0068 Ratio of urine density to water density
Standard Deviation 0.00631
|
0.0036 Ratio of urine density to water density
Standard Deviation 0.00825
|
PRIMARY outcome
Timeframe: At 72 hours of each Treatment PeriodPopulation: Safety Population.
Urine samples were collected to assess urine bilirubin, urine glucose, urine ketones, urine occult blood, urine protein and urine urobilinogen by dipstick test. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameter of urine bilirubin, urine occult blood, urine glucose, urine ketones, urine protein and urine urobilinogen can be read as negative (-) and trace (+-) indicating proportional concentrations in the urine sample.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Number of Participants With Abnormal Urinalysis Results by Dipstick Method
Bilirubin, 72 hours, negative
|
12 Participants
|
12 Participants
|
12 Participants
|
12 Participants
|
|
Number of Participants With Abnormal Urinalysis Results by Dipstick Method
Glucose, 72 hours, negative
|
12 Participants
|
12 Participants
|
12 Participants
|
12 Participants
|
|
Number of Participants With Abnormal Urinalysis Results by Dipstick Method
Ketones, 72 hours, negative
|
12 Participants
|
12 Participants
|
12 Participants
|
12 Participants
|
|
Number of Participants With Abnormal Urinalysis Results by Dipstick Method
Occult Blood, 72 hours, negative
|
12 Participants
|
12 Participants
|
12 Participants
|
12 Participants
|
|
Number of Participants With Abnormal Urinalysis Results by Dipstick Method
Protein, 72 hours, negative
|
12 Participants
|
12 Participants
|
12 Participants
|
12 Participants
|
|
Number of Participants With Abnormal Urinalysis Results by Dipstick Method
Urobilinogen, 72 hours, trace
|
12 Participants
|
12 Participants
|
12 Participants
|
12 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment PeriodPopulation: Safety Population.
Full 12-lead ECGs were recorded in participant using an automated ECG machine. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate
2 hours
|
3.1 Beats per minute
Standard Deviation 5.20
|
2.9 Beats per minute
Standard Deviation 4.54
|
0.6 Beats per minute
Standard Deviation 3.78
|
2.0 Beats per minute
Standard Deviation 5.86
|
|
Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate
7 hours
|
10.7 Beats per minute
Standard Deviation 5.21
|
9.6 Beats per minute
Standard Deviation 4.72
|
9.0 Beats per minute
Standard Deviation 5.53
|
10.8 Beats per minute
Standard Deviation 7.79
|
|
Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate
14 hours
|
6.9 Beats per minute
Standard Deviation 3.18
|
7.3 Beats per minute
Standard Deviation 4.20
|
7.7 Beats per minute
Standard Deviation 5.35
|
8.3 Beats per minute
Standard Deviation 4.18
|
|
Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate
24 hours
|
3.0 Beats per minute
Standard Deviation 4.31
|
2.3 Beats per minute
Standard Deviation 4.03
|
2.1 Beats per minute
Standard Deviation 6.79
|
1.8 Beats per minute
Standard Deviation 4.82
|
|
Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate
48 hours
|
0.6 Beats per minute
Standard Deviation 3.99
|
3.7 Beats per minute
Standard Deviation 3.31
|
1.3 Beats per minute
Standard Deviation 6.96
|
2.3 Beats per minute
Standard Deviation 7.62
|
|
Change From Baseline in Electrocardiogram (ECG) Finding: Mean Heart Rate
72 hours
|
6.2 Beats per minute
Standard Deviation 5.57
|
5.9 Beats per minute
Standard Deviation 3.20
|
3.7 Beats per minute
Standard Deviation 6.05
|
8.3 Beats per minute
Standard Deviation 5.87
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment PeriodPopulation: Safety Population.
Full 12-lead ECGs were recorded in participants using an automated ECG machine and measured PR, QRS, QT and QTcF intervals. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
PR interval, 2 hours
|
-3.7 Milliseconds
Standard Deviation 8.22
|
-2.3 Milliseconds
Standard Deviation 7.62
|
0.5 Milliseconds
Standard Deviation 8.36
|
-4.0 Milliseconds
Standard Deviation 7.48
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
PR interval, 7 hours
|
-9.5 Milliseconds
Standard Deviation 13.70
|
-8.3 Milliseconds
Standard Deviation 7.95
|
-3.8 Milliseconds
Standard Deviation 11.77
|
-7.0 Milliseconds
Standard Deviation 10.04
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
PR interval, 14 hours
|
-7.5 Milliseconds
Standard Deviation 9.95
|
-0.8 Milliseconds
Standard Deviation 11.92
|
-0.2 Milliseconds
Standard Deviation 10.77
|
-4.2 Milliseconds
Standard Deviation 11.00
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
PR interval, 24 hours
|
1.2 Milliseconds
Standard Deviation 7.26
|
-0.2 Milliseconds
Standard Deviation 8.07
|
1.7 Milliseconds
Standard Deviation 9.18
|
1.5 Milliseconds
Standard Deviation 13.32
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
PR interval, 48 hours
|
2.0 Milliseconds
Standard Deviation 13.75
|
1.0 Milliseconds
Standard Deviation 9.89
|
2.8 Milliseconds
Standard Deviation 11.98
|
3.7 Milliseconds
Standard Deviation 7.33
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
PR interval, 72 hours
|
-0.2 Milliseconds
Standard Deviation 15.92
|
1.2 Milliseconds
Standard Deviation 8.20
|
2.0 Milliseconds
Standard Deviation 13.43
|
4.8 Milliseconds
Standard Deviation 13.47
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
QRS duration, 2 hours
|
-2.3 Milliseconds
Standard Deviation 6.60
|
-2.7 Milliseconds
Standard Deviation 7.69
|
-2.2 Milliseconds
Standard Deviation 7.16
|
0.3 Milliseconds
Standard Deviation 4.89
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
QRS duration, 7 hours
|
0.7 Milliseconds
Standard Deviation 6.95
|
-0.5 Milliseconds
Standard Deviation 4.52
|
-0.5 Milliseconds
Standard Deviation 6.39
|
1.7 Milliseconds
Standard Deviation 4.33
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
QRS duration, 14 hours
|
3.5 Milliseconds
Standard Deviation 8.40
|
0.8 Milliseconds
Standard Deviation 1.59
|
0.3 Milliseconds
Standard Deviation 5.52
|
1.5 Milliseconds
Standard Deviation 7.34
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
QRS duration, 24 hours
|
1.3 Milliseconds
Standard Deviation 5.14
|
0.7 Milliseconds
Standard Deviation 3.34
|
-1.3 Milliseconds
Standard Deviation 7.74
|
0.7 Milliseconds
Standard Deviation 5.99
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
QRS duration, 48 hours
|
1.0 Milliseconds
Standard Deviation 6.12
|
-1.3 Milliseconds
Standard Deviation 5.28
|
-0.2 Milliseconds
Standard Deviation 10.50
|
-2.5 Milliseconds
Standard Deviation 5.13
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
QRS duration, 72 hours
|
1.0 Milliseconds
Standard Deviation 4.47
|
0.2 Milliseconds
Standard Deviation 5.62
|
1.0 Milliseconds
Standard Deviation 8.33
|
0.3 Milliseconds
Standard Deviation 4.96
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
QT interval, 2 hours
|
-8.0 Milliseconds
Standard Deviation 13.56
|
-3.2 Milliseconds
Standard Deviation 22.94
|
-9.8 Milliseconds
Standard Deviation 20.69
|
-4.7 Milliseconds
Standard Deviation 17.53
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
QT interval, 7 hours
|
-22.7 Milliseconds
Standard Deviation 18.79
|
-29.7 Milliseconds
Standard Deviation 15.06
|
-22.2 Milliseconds
Standard Deviation 22.33
|
-31.3 Milliseconds
Standard Deviation 24.10
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
QT interval, 14 hours
|
-20.5 Milliseconds
Standard Deviation 17.35
|
-21.3 Milliseconds
Standard Deviation 17.55
|
-20.0 Milliseconds
Standard Deviation 20.47
|
-23.5 Milliseconds
Standard Deviation 20.91
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
QT interval, 24 hours
|
-8.3 Milliseconds
Standard Deviation 13.59
|
0.7 Milliseconds
Standard Deviation 14.95
|
-13.5 Milliseconds
Standard Deviation 16.65
|
-6.7 Milliseconds
Standard Deviation 13.84
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
QT interval, 48 hours
|
-3.3 Milliseconds
Standard Deviation 9.55
|
-7.3 Milliseconds
Standard Deviation 10.39
|
-15.2 Milliseconds
Standard Deviation 20.85
|
-15.7 Milliseconds
Standard Deviation 17.24
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
QT interval, 72 hours
|
-18.0 Milliseconds
Standard Deviation 17.20
|
-11.8 Milliseconds
Standard Deviation 13.42
|
-14.7 Milliseconds
Standard Deviation 20.44
|
-23.3 Milliseconds
Standard Deviation 12.69
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
QTcF interval, 2 hours
|
-0.1 Milliseconds
Standard Deviation 16.40
|
4.0 Milliseconds
Standard Deviation 19.41
|
-7.1 Milliseconds
Standard Deviation 18.60
|
0.6 Milliseconds
Standard Deviation 17.64
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
QTcF interval, 7 hours
|
2.1 Milliseconds
Standard Deviation 15.02
|
-6.7 Milliseconds
Standard Deviation 15.07
|
-1.4 Milliseconds
Standard Deviation 16.59
|
-7.2 Milliseconds
Standard Deviation 14.83
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
QTcF interval, 14 hours
|
-3.6 Milliseconds
Standard Deviation 16.50
|
-3.8 Milliseconds
Standard Deviation 12.75
|
-1.4 Milliseconds
Standard Deviation 13.94
|
-4.8 Milliseconds
Standard Deviation 15.60
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
QTcF interval, 24 hours
|
-0.5 Milliseconds
Standard Deviation 14.44
|
7.8 Milliseconds
Standard Deviation 15.82
|
-7.8 Milliseconds
Standard Deviation 19.60
|
-1.8 Milliseconds
Standard Deviation 9.04
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
QTcF interval, 48 hours
|
-1.9 Milliseconds
Standard Deviation 13.55
|
1.9 Milliseconds
Standard Deviation 7.18
|
-11.3 Milliseconds
Standard Deviation 12.20
|
-10.0 Milliseconds
Standard Deviation 16.31
|
|
Change From Baseline in ECG Findings of TID Doses for One Day of GSK2982772
QTcF interval, 72 hours
|
-2.9 Milliseconds
Standard Deviation 12.92
|
2.6 Milliseconds
Standard Deviation 11.37
|
-4.8 Milliseconds
Standard Deviation 13.30
|
-4.5 Milliseconds
Standard Deviation 12.26
|
PRIMARY outcome
Timeframe: Up to 24 hours at each Treatment PeriodPopulation: Safety Population.
Continuous cardiac telemetry was performed and number of participants with abnormal clinically significant and not clinically significant values are presented.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Number of Participants With Abnormal Not Clinically Significant Cardiac Telemetry
Abnormal-clinically significant
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Abnormal Not Clinically Significant Cardiac Telemetry
Abnormal-not clinically significant
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each treatment periodPopulation: Safety Population.
Blood pressure of participants were measured at indicated time points in supine position after 5 minutes rest. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, 24 hours
|
-2.2 Millimeters of mercury
Standard Deviation 6.15
|
0.3 Millimeters of mercury
Standard Deviation 6.41
|
-4.0 Millimeters of mercury
Standard Deviation 5.24
|
-2.4 Millimeters of mercury
Standard Deviation 10.21
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, 72 hours
|
1.9 Millimeters of mercury
Standard Deviation 9.23
|
2.3 Millimeters of mercury
Standard Deviation 8.57
|
3.8 Millimeters of mercury
Standard Deviation 7.57
|
4.5 Millimeters of mercury
Standard Deviation 5.04
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, 2 hours
|
0.2 Millimeters of mercury
Standard Deviation 5.13
|
-2.5 Millimeters of mercury
Standard Deviation 7.22
|
-1.9 Millimeters of mercury
Standard Deviation 5.73
|
-2.2 Millimeters of mercury
Standard Deviation 8.09
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, 7 hours
|
-7.3 Millimeters of mercury
Standard Deviation 6.75
|
-7.0 Millimeters of mercury
Standard Deviation 8.12
|
-8.2 Millimeters of mercury
Standard Deviation 8.33
|
-5.9 Millimeters of mercury
Standard Deviation 8.75
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, 14 hours
|
-4.4 Millimeters of mercury
Standard Deviation 5.16
|
-5.3 Millimeters of mercury
Standard Deviation 8.29
|
-6.9 Millimeters of mercury
Standard Deviation 5.88
|
-4.3 Millimeters of mercury
Standard Deviation 8.88
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, 48 hours
|
-1.3 Millimeters of mercury
Standard Deviation 6.88
|
1.3 Millimeters of mercury
Standard Deviation 5.83
|
-0.3 Millimeters of mercury
Standard Deviation 4.69
|
0.5 Millimeters of mercury
Standard Deviation 9.30
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, 72 hours
|
-0.2 Millimeters of mercury
Standard Deviation 5.25
|
0.3 Millimeters of mercury
Standard Deviation 6.66
|
-0.1 Millimeters of mercury
Standard Deviation 7.18
|
2.8 Millimeters of mercury
Standard Deviation 10.84
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, 2 hours
|
1.3 Millimeters of mercury
Standard Deviation 6.85
|
0.4 Millimeters of mercury
Standard Deviation 7.55
|
2.4 Millimeters of mercury
Standard Deviation 4.10
|
0.6 Millimeters of mercury
Standard Deviation 5.30
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, 7 hours
|
-0.3 Millimeters of mercury
Standard Deviation 8.99
|
2.5 Millimeters of mercury
Standard Deviation 6.65
|
-0.7 Millimeters of mercury
Standard Deviation 8.15
|
1.3 Millimeters of mercury
Standard Deviation 6.09
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, 14 hours
|
3.3 Millimeters of mercury
Standard Deviation 5.76
|
1.0 Millimeters of mercury
Standard Deviation 6.06
|
9.0 Millimeters of mercury
Standard Deviation 11.24
|
5.6 Millimeters of mercury
Standard Deviation 11.12
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, 24 hours
|
0.3 Millimeters of mercury
Standard Deviation 4.70
|
0.1 Millimeters of mercury
Standard Deviation 5.55
|
1.4 Millimeters of mercury
Standard Deviation 6.07
|
2.9 Millimeters of mercury
Standard Deviation 5.93
|
|
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, 48 hours
|
0.8 Millimeters of mercury
Standard Deviation 6.05
|
-0.3 Millimeters of mercury
Standard Deviation 6.24
|
1.2 Millimeters of mercury
Standard Deviation 4.26
|
-1.1 Millimeters of mercury
Standard Deviation 5.52
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment PeriodPopulation: Safety Population.
Pulse rate of participants were measured at indicated time points in supine position after 5 minutes rest. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772
72 hours
|
-0.4 Beats per minute
Standard Deviation 6.57
|
5.0 Beats per minute
Standard Deviation 3.79
|
2.2 Beats per minute
Standard Deviation 4.91
|
6.0 Beats per minute
Standard Deviation 5.48
|
|
Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772
2 hours
|
0.9 Beats per minute
Standard Deviation 5.35
|
1.7 Beats per minute
Standard Deviation 4.19
|
0.4 Beats per minute
Standard Deviation 4.10
|
0.8 Beats per minute
Standard Deviation 3.81
|
|
Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772
7 hours
|
6.9 Beats per minute
Standard Deviation 4.17
|
9.4 Beats per minute
Standard Deviation 5.60
|
8.9 Beats per minute
Standard Deviation 5.92
|
10.4 Beats per minute
Standard Deviation 6.75
|
|
Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772
14 hours
|
3.3 Beats per minute
Standard Deviation 3.50
|
5.3 Beats per minute
Standard Deviation 3.58
|
5.5 Beats per minute
Standard Deviation 4.44
|
8.3 Beats per minute
Standard Deviation 4.50
|
|
Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772
24 hours
|
-0.9 Beats per minute
Standard Deviation 4.74
|
1.0 Beats per minute
Standard Deviation 3.64
|
1.1 Beats per minute
Standard Deviation 2.75
|
3.3 Beats per minute
Standard Deviation 4.11
|
|
Change From Baseline in Pulse Rate of TID Doses for One Day of GSK2982772
48 hours
|
-1.7 Beats per minute
Standard Deviation 3.98
|
1.5 Beats per minute
Standard Deviation 3.37
|
1.3 Beats per minute
Standard Deviation 4.97
|
4.3 Beats per minute
Standard Deviation 5.45
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment PeriodPopulation: Safety Population.
Temperature of participants were measured at indicated time points in supine position after 5 minutes rest. Baseline value was the latest pre-dose (Day -1) assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is calculated as the value at the post-dose visit minus the Baseline value.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772
2 hours
|
0.22 Degrees Celsius
Standard Deviation 0.204
|
0.32 Degrees Celsius
Standard Deviation 0.199
|
0.12 Degrees Celsius
Standard Deviation 0.241
|
0.18 Degrees Celsius
Standard Deviation 0.276
|
|
Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772
7 hours
|
0.47 Degrees Celsius
Standard Deviation 0.274
|
0.51 Degrees Celsius
Standard Deviation 0.231
|
0.43 Degrees Celsius
Standard Deviation 0.261
|
0.48 Degrees Celsius
Standard Deviation 0.366
|
|
Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772
14 hours
|
0.39 Degrees Celsius
Standard Deviation 0.264
|
0.48 Degrees Celsius
Standard Deviation 0.191
|
0.40 Degrees Celsius
Standard Deviation 0.388
|
0.65 Degrees Celsius
Standard Deviation 0.258
|
|
Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772
24 hours
|
0.07 Degrees Celsius
Standard Deviation 0.223
|
-0.05 Degrees Celsius
Standard Deviation 0.239
|
0.08 Degrees Celsius
Standard Deviation 0.237
|
0.08 Degrees Celsius
Standard Deviation 0.286
|
|
Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772
48 hours
|
0.06 Degrees Celsius
Standard Deviation 0.297
|
-0.07 Degrees Celsius
Standard Deviation 0.235
|
-0.08 Degrees Celsius
Standard Deviation 0.222
|
0.12 Degrees Celsius
Standard Deviation 0.292
|
|
Change From Baseline in Body Temperature of TID Doses for One Day of GSK2982772
72 hours
|
0.09 Degrees Celsius
Standard Deviation 0.257
|
0.00 Degrees Celsius
Standard Deviation 0.191
|
0.09 Degrees Celsius
Standard Deviation 0.284
|
0.24 Degrees Celsius
Standard Deviation 0.271
|
PRIMARY outcome
Timeframe: Baseline (Day -1) and at 2, 7, 14, 24, 48 and 72 hours at each Treatment PeriodPopulation: Safety Population.
Neurological examinations including: mental status, gait, balance, coordination, cranial nerves, motor power, reflexes, and sensory system (light touch and pain) were assessed in participants specified time points.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
n=12 Participants
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Number of Participants With Abnormal Neurological Examinations of TID Doses for One Day of GSK2982772
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Pre-dose, 20 and 40 minutes, 1, 1.5, 2, 3, 5, 7 hours, 7 hours 20 minutes, 7 hours 40 minutes, 8, 8.5, 9, 10, 12, 14 hours, 14 hours 20 minutes, 14 hours 40 minutes, 15, 15.5, 16, 17, 19, 22 and 24 hours post-dose at each Treatment PeriodPopulation: Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Blood samples were collected from participants at indicated time points and analyzed for AUC (0-24) and AUC over each dose: AUC(0-7), AUC (7-14) and AUC (14-24) after the administration of TID doses of GSK2982772. Pharmacokinetic analysis was conducted using standard non-compartmental methods. All participants in the safety population for whom a pharmacokinetic sample has been obtained and analyzed was included in the pharmacokinetic population.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Area Under the Plasma Drug Concentration Versus Time Curve Over 24 Hours (AUC[0-24]) and AUC Over Each Dose Interval of TID Doses for One Day of GSK2982772
AUC (0-24), n=12, 12, 12
|
13.153 Hours*microgram per milliliter
Geometric Coefficient of Variation 22.4
|
25.779 Hours*microgram per milliliter
Geometric Coefficient of Variation 17.7
|
54.960 Hours*microgram per milliliter
Geometric Coefficient of Variation 19.0
|
—
|
|
Area Under the Plasma Drug Concentration Versus Time Curve Over 24 Hours (AUC[0-24]) and AUC Over Each Dose Interval of TID Doses for One Day of GSK2982772
AUC (0-7), TID dose 1, n=10, 10, 7
|
3.804 Hours*microgram per milliliter
Geometric Coefficient of Variation 22.4
|
6.553 Hours*microgram per milliliter
Geometric Coefficient of Variation 22.6
|
10.854 Hours*microgram per milliliter
Geometric Coefficient of Variation 26.6
|
—
|
|
Area Under the Plasma Drug Concentration Versus Time Curve Over 24 Hours (AUC[0-24]) and AUC Over Each Dose Interval of TID Doses for One Day of GSK2982772
AUC (7-14), TID dose 2, n=10, 6, 8
|
4.684 Hours*microgram per milliliter
Geometric Coefficient of Variation 18.7
|
9.200 Hours*microgram per milliliter
Geometric Coefficient of Variation 18.6
|
20.875 Hours*microgram per milliliter
Geometric Coefficient of Variation 20.5
|
—
|
|
Area Under the Plasma Drug Concentration Versus Time Curve Over 24 Hours (AUC[0-24]) and AUC Over Each Dose Interval of TID Doses for One Day of GSK2982772
AUC (14-24), TID dose 3, n=12, 12, 12
|
4.919 Hours*microgram per milliliter
Geometric Coefficient of Variation 24.9
|
10.105 Hours*microgram per milliliter
Geometric Coefficient of Variation 20.8
|
23.602 Hours*microgram per milliliter
Geometric Coefficient of Variation 16.8
|
—
|
SECONDARY outcome
Timeframe: Pre-dose,20 and 40 minutes, 1, 1.5, 2, 3, 5, 7 hours,7 hours 20 minutes,7 hours 40 minutes,8, 8.5, 9, 10, 12, 14 hours,14 hours 20 minutes,14 hours40 minutes, 15, 15.5, 16, 17, 19, 22, 24, 28, 32, 36, 48, 60 and 72 hours post-dose at each Treatment PeriodPopulation: Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
Blood samples were collected from participants at indicated time points and analyzed for Cmax and observed trough drug plasma concentrations: C0, C7, C14 and C24 after the administration of TID doses of GSK2982772.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772
Cmax, TID dose 1, n=12, 12, 12
|
1.187 Micrograms per milliliter
Geometric Coefficient of Variation 16.2
|
2.003 Micrograms per milliliter
Geometric Coefficient of Variation 27.7
|
3.038 Micrograms per milliliter
Geometric Coefficient of Variation 27.5
|
—
|
|
Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772
Cmax, TID dose 2, n=12, 12, 12
|
1.322 Micrograms per milliliter
Geometric Coefficient of Variation 34.2
|
2.727 Micrograms per milliliter
Geometric Coefficient of Variation 21.2
|
5.516 Micrograms per milliliter
Geometric Coefficient of Variation 21.1
|
—
|
|
Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772
Cmax, TID dose 3, n=12, 12, 12
|
1.076 Micrograms per milliliter
Geometric Coefficient of Variation 32.9
|
2.378 Micrograms per milliliter
Geometric Coefficient of Variation 17.8
|
5.120 Micrograms per milliliter
Geometric Coefficient of Variation 13.2
|
—
|
|
Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772
C7, TID dose 1, n=12, 12, 12
|
0.149 Micrograms per milliliter
Geometric Coefficient of Variation 55.3
|
0.344 Micrograms per milliliter
Geometric Coefficient of Variation 41.5
|
0.878 Micrograms per milliliter
Geometric Coefficient of Variation 54.7
|
—
|
|
Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772
C14, TID dose 2, n=12, 12, 12
|
0.175 Micrograms per milliliter
Geometric Coefficient of Variation 44.0
|
0.439 Micrograms per milliliter
Geometric Coefficient of Variation 44.6
|
0.999 Micrograms per milliliter
Geometric Coefficient of Variation 26.5
|
—
|
|
Maximum Observed Plasma Concentration (Cmax) and Observed Trough Drug Plasma Concentrations Following Each TID Doses for One Day of GSK2982772
C24, TID dose 3, n=12, 12, 12
|
0.107 Micrograms per milliliter
Geometric Coefficient of Variation 44.7
|
0.229 Micrograms per milliliter
Geometric Coefficient of Variation 53.3
|
0.543 Micrograms per milliliter
Geometric Coefficient of Variation 47.6
|
—
|
SECONDARY outcome
Timeframe: Pre-dose,20 and 40 minutes, 1, 1.5, 2, 3, 5, 7 hours,7 hours 20 minutes,7 hours 40 minutes,8, 8.5, 9, 10, 12, 14 hours,14 hours 20 minutes,14 hours40 minutes, 15, 15.5, 16, 17, 19, 22, 24, 28, 32, 36, 48, 60 and 72 hours post-dose at each Treatment PeriodPopulation: Pharmacokinetic Population. Only those participants with data available at the specified data points were analyzed.
Blood samples were collected from participants at indicated time points and t1/2 was analyzed after the administration of third TID dose of GSK2982772.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=11 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Terminal Half Life (t1/2) After the Third TID Dose for One Day of GSK2982772
|
5.883 Hours
Geometric Coefficient of Variation 52.5
|
7.206 Hours
Geometric Coefficient of Variation 31.9
|
6.624 Hours
Geometric Coefficient of Variation 51.8
|
—
|
SECONDARY outcome
Timeframe: Pre-dose,20 and 40 minutes, 1, 1.5, 2, 3, 5, 7 hours,7 hours 20 minutes,7 hours 40 minutes,8, 8.5, 9, 10, 12, 14 hours,14 hours 20 minutes,14 hours40 minutes, 15, 15.5, 16, 17, 19, 22, 24, 28, 32, 36, 48, 60 and 72 hours post-dose at each Treatment PeriodPopulation: Pharmacokinetic Population.
Blood samples were collected from participants at indicated time points and Tmax was analyzed after the administration of TID doses of GSK2982772.
Outcome measures
| Measure |
Placebo
n=12 Participants
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 60 mg
n=12 Participants
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 120 mg
n=12 Participants
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP.
|
GSK2982772 240 mg
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP.
|
|---|---|---|---|---|
|
Time to Maximum Observed Plasma Drug Concentration (Tmax) of Each TID Doses for One Day of GSK2982772
TID dose 1
|
2.000 Hours
Interval 1.0 to 3.0
|
1.750 Hours
Interval 1.0 to 3.0
|
2.000 Hours
Interval 1.5 to 5.0
|
—
|
|
Time to Maximum Observed Plasma Drug Concentration (Tmax) of Each TID Doses for One Day of GSK2982772
TID dose 2
|
1.750 Hours
Interval 1.0 to 3.0
|
2.500 Hours
Interval 1.5 to 5.0
|
2.000 Hours
Interval 1.5 to 3.0
|
—
|
|
Time to Maximum Observed Plasma Drug Concentration (Tmax) of Each TID Doses for One Day of GSK2982772
TID dose 3
|
2.500 Hours
Interval 0.67 to 5.0
|
3.000 Hours
Interval 1.0 to 5.0
|
3.000 Hours
Interval 2.0 to 3.0
|
—
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
GSK2982772 60 mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
GSK2982772 120 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
GSK2982772 240 mg
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 |
Placebo
n=12 participants at risk
Participants were administered PBO matching GSK2982772 via oral route using a 7 hours dosing interval in each TP
|
GSK2982772 60 mg
n=12 participants at risk
Participants were administered GSK2982772 60 mg via oral route using a 7 hours dosing interval in each TP
|
GSK2982772 120 mg
n=12 participants at risk
Participants were administered GSK2982772 120 mg via oral route using a 7 hours dosing interval in each TP
|
GSK2982772 240 mg
n=12 participants at risk
Participants were administered GSK2982772 240 mg via oral route using a 7 hours dosing interval in each TP
|
|---|---|---|---|---|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/12 • Non-serious AEs and SAEs were collected from the start of the treatment up to 39 days
Non-serious AEs and SAEs were collected for Safety population
|
8.3%
1/12 • Number of events 1 • Non-serious AEs and SAEs were collected from the start of the treatment up to 39 days
Non-serious AEs and SAEs were collected for Safety population
|
0.00%
0/12 • Non-serious AEs and SAEs were collected from the start of the treatment up to 39 days
Non-serious AEs and SAEs were collected for Safety population
|
0.00%
0/12 • Non-serious AEs and SAEs were collected from the start of the treatment up to 39 days
Non-serious AEs and SAEs were collected for Safety population
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/12 • Non-serious AEs and SAEs were collected from the start of the treatment up to 39 days
Non-serious AEs and SAEs were collected for Safety population
|
8.3%
1/12 • Number of events 1 • Non-serious AEs and SAEs were collected from the start of the treatment up to 39 days
Non-serious AEs and SAEs were collected for Safety population
|
0.00%
0/12 • Non-serious AEs and SAEs were collected from the start of the treatment up to 39 days
Non-serious AEs and SAEs were collected for Safety population
|
0.00%
0/12 • Non-serious AEs and SAEs were collected from the start of the treatment up to 39 days
Non-serious AEs and SAEs were collected for Safety population
|
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