Trial Outcomes & Findings for A Clinical Trial to Test a Study Drug in Volunteers Who Develop Asthma Following Exercise (NCT NCT00812929)
NCT ID: NCT00812929
Last Updated: 2017-09-19
Results Overview
FEV1 was recorded in triplicate, with participant encouraged to inhale fully despite any presence of chest tightness. For FEV1, a pre-challenge Baseline was defined for each challenge time point as maximum of triplicate measurements performed prior to challenge. The maximal percentage change within 60 minutes following exercise challenge was derived by taking minimum (i.e., most negative) percentage change in FEV1 over 5, 10, 15, 30, 45 and 60 minutes post challenge. Percent change FEV1 = 100\*(FEV1 - Pre-challenge FEV1)/ Pre-challenge FEV1. If the exercise challenge was not completed successfully (i.e. heart rate maintained at \>=80% of the predicted value for 6 minutes), FEV1 maximal percent change (0-60)was set to be missing. Analysis was performed using a mixed effects model, including period, treatment and covariates for predose FEV1. Estimates and 95% confidence intervals for treatment difference between each active dose and placebo for each challenge time point were calculated.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
47 participants
Primary outcome timeframe
Baseline (pre dose) and 60 minutes following the exercise challenge at 24 hours post dose of each treatment period.
Results posted on
2017-09-19
Participant Flow
This was a Phase IIa multi-center study conducted in the United States from 02 December 2008 to 15 July 2009.
A total of 47 participants were randomized in the study who underwent a screening visit of 28 days prior to first dose of study medication.
Participant milestones
| Measure |
P/A/D/B/C
In this sequence participants received treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 1, treatment A of oral single dose of aqueous solution of 10 milligrams (mg) GSK2190915 on Day 1 of treatment period 2, treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 3, treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 4 and treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
A/B/P/C/D
In this sequence participants received treatment A of oral single dose of aqueous solution of 10 mg GSK2190915 on Day 1 of treatment period 1, treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 2, treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 3, treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 4 and treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
B/C/A/D/P
In this sequence participants received treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 1, treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 2, treatment A of oral single dose of aqueous solution of 10 mg GSK2190915 on Day 1 of treatment period 3, treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 4, treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
C/D/B/P/A
In this sequence participants received treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 1, treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 2, treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 3, treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 4, treatment A of oral single dose of aqueous solution of 10 mg GSK2190915 on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
D/P/C/A/B
In this sequence participants received treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 1, treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 2, treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 3, treatment A of oral single dose of aqueous solution of 10 mg GSK2190915 on Day 1 of treatment period 4, treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
C/B/D/A/P
In this sequence participants received treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 1, treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 2, treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 3, treatment A of oral single dose of aqueous solution of 10 mg GSK2190915 on Day 1 of treatment period 4, treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
D/C/P/B/A
In this sequence participants received treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 1, treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 2, treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 3, treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 4, treatment A of oral single dose of aqueous solution of 10 mg GSK2190915 on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
P/D/A/C/B
In this sequence participants received treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 1, treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 2, treatment A of oral single dose of aqueous solution of 10 mg GSK2190915 on Day 1 of treatment period 3, treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 4, treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
A/P/B/D/C
In this sequence participants received treatment A of oral single dose of aqueous solution of 10 mg GSK2190915 on Day 1 of treatment period 1, treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 2, treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 3, treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 4, treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
B/A/C/P/D
In this sequence participants received treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 1, treatment A of oral single dose of aqueous solution of 10 mg GSK2190915 on Day 1 of treatment period 2, treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 3, treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 4, treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Treatment Period 1
STARTED
|
5
|
4
|
5
|
4
|
5
|
5
|
5
|
5
|
4
|
5
|
|
Treatment Period 1
COMPLETED
|
5
|
4
|
5
|
4
|
5
|
5
|
5
|
5
|
4
|
5
|
|
Treatment Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Period 1 (7 Days)
STARTED
|
5
|
4
|
5
|
4
|
5
|
5
|
5
|
5
|
4
|
5
|
|
Washout Period 1 (7 Days)
COMPLETED
|
5
|
4
|
4
|
4
|
5
|
5
|
5
|
5
|
4
|
5
|
|
Washout Period 1 (7 Days)
NOT COMPLETED
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 2
STARTED
|
5
|
4
|
4
|
4
|
5
|
5
|
5
|
5
|
4
|
5
|
|
Treatment Period 2
COMPLETED
|
5
|
4
|
4
|
4
|
5
|
5
|
5
|
5
|
4
|
5
|
|
Treatment Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Period 2 (7 Days)
STARTED
|
5
|
4
|
4
|
4
|
5
|
5
|
5
|
5
|
4
|
5
|
|
Washout Period 2 (7 Days)
COMPLETED
|
5
|
4
|
4
|
4
|
5
|
5
|
5
|
5
|
4
|
4
|
|
Washout Period 2 (7 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Treatment Period 3
STARTED
|
5
|
4
|
4
|
4
|
5
|
5
|
5
|
5
|
4
|
4
|
|
Treatment Period 3
COMPLETED
|
5
|
4
|
4
|
4
|
5
|
5
|
5
|
5
|
4
|
4
|
|
Treatment Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Period 3 (7 Days)
STARTED
|
5
|
4
|
4
|
4
|
5
|
5
|
5
|
5
|
4
|
4
|
|
Washout Period 3 (7 Days)
COMPLETED
|
5
|
4
|
4
|
4
|
5
|
4
|
5
|
5
|
4
|
4
|
|
Washout Period 3 (7 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Treatment Period 4
STARTED
|
5
|
4
|
4
|
4
|
5
|
4
|
5
|
5
|
4
|
4
|
|
Treatment Period 4
COMPLETED
|
5
|
4
|
4
|
4
|
5
|
4
|
5
|
5
|
4
|
4
|
|
Treatment Period 4
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Period 4 (7 Days)
STARTED
|
5
|
4
|
4
|
4
|
5
|
4
|
5
|
5
|
4
|
4
|
|
Washout Period 4 (7 Days)
COMPLETED
|
5
|
4
|
4
|
4
|
5
|
4
|
5
|
5
|
4
|
4
|
|
Washout Period 4 (7 Days)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 5
STARTED
|
5
|
4
|
4
|
4
|
5
|
4
|
5
|
5
|
4
|
4
|
|
Treatment Period 5
COMPLETED
|
5
|
4
|
4
|
4
|
5
|
4
|
5
|
5
|
4
|
4
|
|
Treatment Period 5
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
P/A/D/B/C
In this sequence participants received treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 1, treatment A of oral single dose of aqueous solution of 10 milligrams (mg) GSK2190915 on Day 1 of treatment period 2, treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 3, treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 4 and treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
A/B/P/C/D
In this sequence participants received treatment A of oral single dose of aqueous solution of 10 mg GSK2190915 on Day 1 of treatment period 1, treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 2, treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 3, treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 4 and treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
B/C/A/D/P
In this sequence participants received treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 1, treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 2, treatment A of oral single dose of aqueous solution of 10 mg GSK2190915 on Day 1 of treatment period 3, treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 4, treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
C/D/B/P/A
In this sequence participants received treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 1, treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 2, treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 3, treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 4, treatment A of oral single dose of aqueous solution of 10 mg GSK2190915 on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
D/P/C/A/B
In this sequence participants received treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 1, treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 2, treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 3, treatment A of oral single dose of aqueous solution of 10 mg GSK2190915 on Day 1 of treatment period 4, treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
C/B/D/A/P
In this sequence participants received treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 1, treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 2, treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 3, treatment A of oral single dose of aqueous solution of 10 mg GSK2190915 on Day 1 of treatment period 4, treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
D/C/P/B/A
In this sequence participants received treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 1, treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 2, treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 3, treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 4, treatment A of oral single dose of aqueous solution of 10 mg GSK2190915 on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
P/D/A/C/B
In this sequence participants received treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 1, treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 2, treatment A of oral single dose of aqueous solution of 10 mg GSK2190915 on Day 1 of treatment period 3, treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 4, treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
A/P/B/D/C
In this sequence participants received treatment A of oral single dose of aqueous solution of 10 mg GSK2190915 on Day 1 of treatment period 1, treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 2, treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 3, treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 4, treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
B/A/C/P/D
In this sequence participants received treatment B of oral single dose of aqueous solution of 50 mg GSK2190915 on Day 1 of treatment period 1, treatment A of oral single dose of aqueous solution of 10 mg GSK2190915 on Day 1 of treatment period 2, treatment C of oral single dose of aqueous solution of 100 mg GSK2190915 on Day 1 of treatment period 3, treatment P of oral single dose of aqueous solution of matching placebo on Day 1 of treatment period 4, treatment D of oral single dose of aqueous solution of 200 mg GSK2190915 on Day 1 of treatment period 5. Each treatment periods were separated by a minimum 7 days washout period. Each treatment period included an exercise challenge at 2, 9.5, and 24 hours post dose and concluded on completion of the assessments following exercise challenge at 24 hours post dose.
|
|---|---|---|---|---|---|---|---|---|---|---|
|
Washout Period 1 (7 Days)
Physician Decision
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Period 2 (7 Days)
Physician Decision
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Washout Period 3 (7 Days)
Adverse Event
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
Baseline Characteristics
A Clinical Trial to Test a Study Drug in Volunteers Who Develop Asthma Following Exercise
Baseline characteristics by cohort
| Measure |
Total
n=47 Participants
Eligible participants completed five treatment periods (single dose 10 mg, 50 mg, 100 mg, 200 mg GSK2190915 oral solution, compared to placebo control which was administered on Day 1 of each treatment period). Each treatment period lasted 2 days, with a minimum 7 day washout period between each treatment periods.
|
|---|---|
|
Age, Continuous
|
28.4 Years
STANDARD_DEVIATION 8.57 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
41 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
38 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (pre dose) and 60 minutes following the exercise challenge at 24 hours post dose of each treatment period.Population: The 'Efficacy Population' was defined as all participants who received at least one dose of study medication and are not major protocol violators.
FEV1 was recorded in triplicate, with participant encouraged to inhale fully despite any presence of chest tightness. For FEV1, a pre-challenge Baseline was defined for each challenge time point as maximum of triplicate measurements performed prior to challenge. The maximal percentage change within 60 minutes following exercise challenge was derived by taking minimum (i.e., most negative) percentage change in FEV1 over 5, 10, 15, 30, 45 and 60 minutes post challenge. Percent change FEV1 = 100\*(FEV1 - Pre-challenge FEV1)/ Pre-challenge FEV1. If the exercise challenge was not completed successfully (i.e. heart rate maintained at \>=80% of the predicted value for 6 minutes), FEV1 maximal percent change (0-60)was set to be missing. Analysis was performed using a mixed effects model, including period, treatment and covariates for predose FEV1. Estimates and 95% confidence intervals for treatment difference between each active dose and placebo for each challenge time point were calculated.
Outcome measures
| Measure |
Placebo
n=44 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=45 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=46 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=45 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=45 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Maximal Percentage Change From Pre-exercise Baseline Forced Expiratory Volume in 1 Second (FEV1) to the Minimum FEV1 Collected Within 60 Minutes Following the Exercise Challenge at 24 Hours Post Dose
|
-7.61 Percent change
Standard Error 1.326
|
-6.33 Percent change
Standard Error 1.314
|
-7.09 Percent change
Standard Error 1.307
|
-7.28 Percent change
Standard Error 1.314
|
-5.09 Percent change
Standard Error 1.315
|
SECONDARY outcome
Timeframe: Baseline (pre dose) and 60 minutes following the exercise challenge at 2 and 9.5 hours post dose of each treatment period.Population: Efficacy Population.
FEV1 was recorded in triplicate, with participant encouraged to inhale fully despite any presence of chest tightness. For FEV1, a pre-challenge Baseline was defined for each challenge time point as maximum of triplicate measurements performed prior to challenge. The maximal percentage change within 60 minutes following exercise challenge was derived by taking minimum percentage change in FEV1 over 5, 10, 15, 30, 45 and 60 minutes post challenge. Percent change FEV1 = 100\*(FEV1 - Pre-challenge FEV1)/ Pre-challenge FEV1. If the exercise challenge was not completed successfully (i.e. heart rate maintained at \>=80% of the predicted value for 6 minutes), the FEV1 maximal percent change (0-60)was set to be missing. Analysis was performed using a mixed effects model, including period, treatment and covariates for predose FEV1. Estimates and 95% confidence intervals for treatment difference between each active dose and placebo for each challenge time point were calculated.
Outcome measures
| Measure |
Placebo
n=44 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=45 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=46 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=45 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=45 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Maximal Percentage Change From Pre-exercise Baseline FEV1 to the Minimum FEV1 Collected Within 60 Minutes Following the Exercise Challenge at 2 and 9.5 Hours Post Dose
2 Hours
|
-15.55 Percent change
Standard Error 1.437
|
-13.04 Percent change
Standard Error 1.424
|
-12.95 Percent change
Standard Error 1.416
|
-12.76 Percent change
Standard Error 1.424
|
-9.25 Percent change
Standard Error 1.425
|
|
Maximal Percentage Change From Pre-exercise Baseline FEV1 to the Minimum FEV1 Collected Within 60 Minutes Following the Exercise Challenge at 2 and 9.5 Hours Post Dose
9.5 Hours
|
-8.45 Percent change
Standard Error 1.222
|
-8.33 Percent change
Standard Error 1.212
|
-7.69 Percent change
Standard Error 1.206
|
-4.96 Percent change
Standard Error 1.213
|
-6.18 Percent change
Standard Error 1.213
|
SECONDARY outcome
Timeframe: Baseline (pre dose) and 0 to 60 minutes following exercise challenge at 2, 9.5 and 24 hours post dose of each treatment period.Population: Efficacy Population.
FEV1 was recorded in triplicate, with participant encouraged to inhale fully despite any presence of chest tightness. For FEV1, a pre-challenge Baseline was defined for each challenge time point as maximum of triplicate measurements performed prior to challenge.Weighted mean FEV1 percentage change recorded during 0-60 minutes post challenge was determined for each challenge, by dividing area under curve (AUC) for percent change from Baseline FEV1 measurements at 5, 10, 15, 30, 45 and 60 minutes post challenge by time interval. Actual times were used to determine time interval where available; otherwise planned relative time was used. If one or more FEV1 values were missing, AUC was calculated over time interval of available values. If intermittent values were missing over a participant's profile,it was assumed to be linear between 2 available values for calculation of AUC. Analysis was performed using a mixed effects model, including period, treatment and covariates for predose FEV1.
Outcome measures
| Measure |
Placebo
n=44 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=45 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=46 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=45 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=45 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Weighted Mean (WM) for FEV1 Percentage Change From Baseline Recorded During 0 to 60 Minutes Following Exercise Challenge (FEV1 WM0-60)
9.5 Hours
|
-2.43 Percent change
Standard Error 0.757
|
-2.36 Percent change
Standard Error 0.750
|
-1.21 Percent change
Standard Error 0.745
|
0.87 Percent change
Standard Error 0.750
|
-0.32 Percent change
Standard Error 0.750
|
|
Weighted Mean (WM) for FEV1 Percentage Change From Baseline Recorded During 0 to 60 Minutes Following Exercise Challenge (FEV1 WM0-60)
2 Hours
|
-5.20 Percent change
Standard Error 0.936
|
-4.26 Percent change
Standard Error 0.926
|
-4.08 Percent change
Standard Error 0.920
|
-3.69 Percent change
Standard Error 0.926
|
-2.04 Percent change
Standard Error 0.927
|
|
Weighted Mean (WM) for FEV1 Percentage Change From Baseline Recorded During 0 to 60 Minutes Following Exercise Challenge (FEV1 WM0-60)
24 Hours
|
-0.25 Percent change
Standard Error 0.755
|
0.65 Percent change
Standard Error 0.747
|
-0.08 Percent change
Standard Error 0.742
|
-0.35 Percent change
Standard Error 0.747
|
1.46 Percent change
Standard Error 0.748
|
SECONDARY outcome
Timeframe: 0 to 60 minutes following exercise challenge at 2, 9.5 and 24 hours post dose of each treatment periodPopulation: Efficacy Population.
The time from maximal percentage change in FEV1 to recovery to within 5% of pre challenge Baseline (in minutes) was derived using actual sampling times. Time to FEV1 recovery= \[SAS date/time of recovery(a) FEV1 - SAS date/time of FEV1 Maximum % Change0-60\] / 60, where "a" is earliest recorded FEV1 either above pre-challenge Baseline or within 5% below pre challenge Baseline. Any unscheduled FEV1 measurements taken after last scheduled post challenge measurement was considered when deriving this endpoint. A corresponding censoring variable was derived for analysis to indicate whether recovery to within 5% of pre-challenge Baseline was achieved. The censoring variable was set to 1 if recovery to within 5% of Baseline was achieved. If recovery was not evident from data collected, time to recovery was calculated using the date/time of the last available post challenge FEV1 assessment and censoring variable was set to zero. Analysis was performed using a Cox proportional hazards model.
Outcome measures
| Measure |
Placebo
n=44 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=45 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=46 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=45 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=45 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Time to FEV1 Recovery to Within 5 Percent of Baseline Following Exercise Challenge
9.5 Hours
|
5.0 Minutes
Interval 0.0 to 18.0
|
9.0 Minutes
Interval 0.0 to 25.0
|
5.0 Minutes
Interval 0.0 to 10.0
|
0.0 Minutes
Interval 0.0 to 5.0
|
0.0 Minutes
Interval 0.0 to 5.0
|
|
Time to FEV1 Recovery to Within 5 Percent of Baseline Following Exercise Challenge
24 Hours
|
5.0 Minutes
Interval 0.0 to 16.0
|
0.0 Minutes
Interval 0.0 to 5.0
|
2.5 Minutes
Interval 0.0 to 6.0
|
5.0 Minutes
Interval 0.0 to 5.0
|
0.0 Minutes
Interval 0.0 to 5.0
|
|
Time to FEV1 Recovery to Within 5 Percent of Baseline Following Exercise Challenge
2 Hours
|
24.5 Minutes
Interval 15.0 to 36.0
|
15.0 Minutes
Interval 10.0 to 30.0
|
18.0 Minutes
Interval 5.0 to 35.0
|
10.0 Minutes
Interval 5.0 to 16.0
|
5.0 Minutes
Interval 0.0 to 12.0
|
SECONDARY outcome
Timeframe: 0 to 90 minutes following exercise challenge of each treatment periodPopulation: Efficacy Population.
Rescue medication was provided to participants at any time and it was strongly recommended for participants with a FEV1 decrease of at least 40% following exercise challenge compared to Baseline. Rescue medication was administered 0 to 90 minutes post exercise challenge. Statistical analysis was supposed to be performed using logistic regression, however, the data was too sparse to permit any formal statistical analysis.
Outcome measures
| Measure |
Placebo
n=44 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=45 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=46 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=45 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=45 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Number of Participants Using a Short Acting Beta-2 Agonist (Rescue Medication) During 0 to 90 Minutes Following Exercise Challenge
9.5 Hours
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Using a Short Acting Beta-2 Agonist (Rescue Medication) During 0 to 90 Minutes Following Exercise Challenge
2 Hours
|
1 Participants
|
1 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants Using a Short Acting Beta-2 Agonist (Rescue Medication) During 0 to 90 Minutes Following Exercise Challenge
24 Hours
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Pre dose, 2 hours, 9.5 hours and 24 hours prior to exercise challenge of treatment periodPopulation: All Subjects Population was defined as all participants who received at least one dose of study medication.
All participants rested for at least 10 minutes in the supine position prior to vital signs recordings. Vital signs Baseline values for SBP and DBP for each treatment period were calculated using the mean value of triplicate pre dose readings. Triplicate readings were taken at least five minutes apart. Assessment was performed at pre dose, 2 hours, 9.5 hours and 24 hours prior to exercise challenge.
Outcome measures
| Measure |
Placebo
n=44 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=45 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=47 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=45 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=45 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Assessment of Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, 24 Hours, Pre Exercise
|
117.2 Millimeters of mercury (mmHg)
Standard Deviation 11.62
|
116.9 Millimeters of mercury (mmHg)
Standard Deviation 10.73
|
117.4 Millimeters of mercury (mmHg)
Standard Deviation 9.93
|
117.5 Millimeters of mercury (mmHg)
Standard Deviation 11.00
|
119.8 Millimeters of mercury (mmHg)
Standard Deviation 11.50
|
|
Assessment of Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, 9.5 Hours, Pre Exercise
|
71.9 Millimeters of mercury (mmHg)
Standard Deviation 6.05
|
70.5 Millimeters of mercury (mmHg)
Standard Deviation 7.01
|
72.0 Millimeters of mercury (mmHg)
Standard Deviation 7.65
|
71.2 Millimeters of mercury (mmHg)
Standard Deviation 7.79
|
71.9 Millimeters of mercury (mmHg)
Standard Deviation 7.71
|
|
Assessment of Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, 24 Hours, Pre Exercise
|
71.1 Millimeters of mercury (mmHg)
Standard Deviation 7.23
|
72.0 Millimeters of mercury (mmHg)
Standard Deviation 7.84
|
72.2 Millimeters of mercury (mmHg)
Standard Deviation 6.52
|
71.1 Millimeters of mercury (mmHg)
Standard Deviation 8.25
|
72.9 Millimeters of mercury (mmHg)
Standard Deviation 8.85
|
|
Assessment of Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, Mean Pre Dose
|
118.8 Millimeters of mercury (mmHg)
Standard Deviation 10.21
|
117.2 Millimeters of mercury (mmHg)
Standard Deviation 10.45
|
117.6 Millimeters of mercury (mmHg)
Standard Deviation 11.53
|
117.4 Millimeters of mercury (mmHg)
Standard Deviation 11.49
|
118.1 Millimeters of mercury (mmHg)
Standard Deviation 11.33
|
|
Assessment of Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, 2 Hours, Pre Exercise
|
120.1 Millimeters of mercury (mmHg)
Standard Deviation 10.50
|
119.8 Millimeters of mercury (mmHg)
Standard Deviation 11.50
|
119.1 Millimeters of mercury (mmHg)
Standard Deviation 10.48
|
119.4 Millimeters of mercury (mmHg)
Standard Deviation 10.42
|
120.3 Millimeters of mercury (mmHg)
Standard Deviation 11.32
|
|
Assessment of Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
SBP, 9.5 Hours, Pre Exercise
|
119.4 Millimeters of mercury (mmHg)
Standard Deviation 10.50
|
117.0 Millimeters of mercury (mmHg)
Standard Deviation 8.69
|
120.5 Millimeters of mercury (mmHg)
Standard Deviation 11.37
|
119.7 Millimeters of mercury (mmHg)
Standard Deviation 10.58
|
118.4 Millimeters of mercury (mmHg)
Standard Deviation 11.86
|
|
Assessment of Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, Mean Pre Dose
|
71.7 Millimeters of mercury (mmHg)
Standard Deviation 7.37
|
71.9 Millimeters of mercury (mmHg)
Standard Deviation 7.40
|
71.5 Millimeters of mercury (mmHg)
Standard Deviation 7.59
|
71.6 Millimeters of mercury (mmHg)
Standard Deviation 6.65
|
71.9 Millimeters of mercury (mmHg)
Standard Deviation 6.62
|
|
Assessment of Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
DBP, 2 Hours, Pre Exercise
|
71.1 Millimeters of mercury (mmHg)
Standard Deviation 6.93
|
72.2 Millimeters of mercury (mmHg)
Standard Deviation 6.09
|
71.3 Millimeters of mercury (mmHg)
Standard Deviation 7.60
|
71.6 Millimeters of mercury (mmHg)
Standard Deviation 7.76
|
72.2 Millimeters of mercury (mmHg)
Standard Deviation 6.66
|
SECONDARY outcome
Timeframe: Pre dose, 2 hours, 9.5 hours and 24 hours prior to exercise challenge of each treatment periodPopulation: All Subjects Population.
All participants rested for at least 10 minutes in the supine position prior to vital signs recordings. Vital signs Baseline values for HR for each treatment period were calculated using the mean value of triplicate pre dose readings. Triplicate readings were taken at least five minutes apart. Assessment was performed at pre dose, 2 hours, 9.5 hours and 24 hours prior to exercise challenge.
Outcome measures
| Measure |
Placebo
n=44 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=45 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=47 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=45 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=45 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Assessment of Vital Signs: Heart Rate (HR)
Mean Pre Dose
|
64.0 Beats per minute
Standard Deviation 9.20
|
63.0 Beats per minute
Standard Deviation 7.62
|
64.0 Beats per minute
Standard Deviation 7.78
|
63.6 Beats per minute
Standard Deviation 7.48
|
64.7 Beats per minute
Standard Deviation 8.38
|
|
Assessment of Vital Signs: Heart Rate (HR)
24 Hours, Pre Excercise
|
68.3 Beats per minute
Standard Deviation 10.90
|
65.7 Beats per minute
Standard Deviation 8.32
|
67.7 Beats per minute
Standard Deviation 8.75
|
65.9 Beats per minute
Standard Deviation 8.03
|
65.6 Beats per minute
Standard Deviation 9.31
|
|
Assessment of Vital Signs: Heart Rate (HR)
2 Hours, Pre Exercise
|
67.5 Beats per minute
Standard Deviation 8.78
|
66.2 Beats per minute
Standard Deviation 9.08
|
67.2 Beats per minute
Standard Deviation 8.51
|
66.8 Beats per minute
Standard Deviation 6.95
|
67.2 Beats per minute
Standard Deviation 8.98
|
|
Assessment of Vital Signs: Heart Rate (HR)
9.5 Hours, Pre Exercise
|
72.9 Beats per minute
Standard Deviation 11.35
|
69.4 Beats per minute
Standard Deviation 8.97
|
72.8 Beats per minute
Standard Deviation 9.16
|
72.3 Beats per minute
Standard Deviation 8.27
|
69.4 Beats per minute
Standard Deviation 9.46
|
SECONDARY outcome
Timeframe: Pre dose, 2 hours, 9.5 hours and 24 hours prior to exercise challenge and 60 minutes following exercise challenge at 2 hours of each treatment periodPopulation: All Subjects Population.
All participants rested for at least 10 minutes in the supine position prior to ECG recordings. ECG Baseline values for each treatment period was calculated using the mean value of triplicate pre dose readings. Triplicate readings were taken at least five minutes apart. Assessment was performed at pre dose, 2 hours, 9.5 hours, 24 hours prior to exercise challenge and 60 minutes following exercise challenge at 2 hours. Participants with not clinically significant (NCS) abnormal values were reported. Potential clinical importance range for the ECG parameters are as follows: absolute QTc interval \>450 millisecond (msec), increase from Baseline QTc \>60 msec, PR interval \<110 and \>220 msec and QRS interval \<75 and \>110 msec. No participants reported clinically significant abnormal values.
Outcome measures
| Measure |
Placebo
n=44 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=45 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=47 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=45 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=45 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Pre dose 1, Abnormal - NCS
|
15 Participants
|
20 Participants
|
20 Participants
|
18 Participants
|
19 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Pre dose 3, Abnormal - NCS
|
23 Participants
|
21 Participants
|
20 Participants
|
19 Participants
|
22 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
2 Hours, Pre Exercise, Abnormal - NCS
|
21 Participants
|
22 Participants
|
15 Participants
|
19 Participants
|
20 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
2 Hours, 60 minutes, Abnormal - NCS
|
15 Participants
|
21 Participants
|
17 Participants
|
19 Participants
|
20 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
24 Hours, Pre exercise, Abnormal - NCS
|
16 Participants
|
22 Participants
|
19 Participants
|
18 Participants
|
20 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Pre dose 2, Abnormal - NCS
|
17 Participants
|
19 Participants
|
21 Participants
|
18 Participants
|
21 Participants
|
|
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
9.5 Hours, Pre exercise, Abnormal - NCS
|
12 Participants
|
18 Participants
|
17 Participants
|
16 Participants
|
18 Participants
|
SECONDARY outcome
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment periodPopulation: All Subjects Population. Only those participants with data available at the indicated time points were analyzed.
Blood samples were collected for the assessment of clinical chemistry parameters for albumin and total protein at pre dose and 25 hours and 30 minutes. Participants had to fast for at least 8 hours prior to visit. During treatment periods, fasting continued until a light meal was allowed 1 hour post dose.
Outcome measures
| Measure |
Placebo
n=44 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=45 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=47 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=45 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=45 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Assessment of Clinical Chemistry Parameters: Albumin, Total Protein
Albumin, 25Hours 30minutes
|
45.8140 Gram/liter (G/L)
Standard Deviation 2.23879
|
45.4222 Gram/liter (G/L)
Standard Deviation 3.08581
|
45.7021 Gram/liter (G/L)
Standard Deviation 2.43091
|
45.9111 Gram/liter (G/L)
Standard Deviation 2.16188
|
45.8444 Gram/liter (G/L)
Standard Deviation 2.53122
|
|
Assessment of Clinical Chemistry Parameters: Albumin, Total Protein
Total protein, Pre dose 1
|
71.9 Gram/liter (G/L)
Standard Deviation 5.32
|
72.5 Gram/liter (G/L)
Standard Deviation 4.05
|
71.4 Gram/liter (G/L)
Standard Deviation 5.11
|
71.6 Gram/liter (G/L)
Standard Deviation 4.16
|
71.3 Gram/liter (G/L)
Standard Deviation 4.78
|
|
Assessment of Clinical Chemistry Parameters: Albumin, Total Protein
Total protein, 25Hours 30minutes
|
73.2 Gram/liter (G/L)
Standard Deviation 4.00
|
72.9 Gram/liter (G/L)
Standard Deviation 3.59
|
73.5 Gram/liter (G/L)
Standard Deviation 3.97
|
72.6 Gram/liter (G/L)
Standard Deviation 2.73
|
72.8 Gram/liter (G/L)
Standard Deviation 3.72
|
|
Assessment of Clinical Chemistry Parameters: Albumin, Total Protein
Albumin, Pre dose 1
|
44.5000 Gram/liter (G/L)
Standard Deviation 3.30961
|
44.9091 Gram/liter (G/L)
Standard Deviation 2.60427
|
44.4894 Gram/liter (G/L)
Standard Deviation 3.24956
|
44.8667 Gram/liter (G/L)
Standard Deviation 2.54594
|
44.9778 Gram/liter (G/L)
Standard Deviation 3.20148
|
SECONDARY outcome
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment periodPopulation: All Subjects Population. Only those participants available at the indicated time points were analyzed.
Blood samples were collected for the assessment of clinical chemistry parameters for ALP, ALT, AST and GGT at pre dose and 25 hours and 30 minutes. Participants had to fast for at least 8 hours prior to visit. During treatment periods, fasting continued until a light meal was allowed 1 hour post dose.
Outcome measures
| Measure |
Placebo
n=44 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=45 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=47 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=45 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=45 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Assessment of Clinical Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT)
ALP, Pre dose 1
|
76.6 International units per liter (IU/L)
Standard Deviation 26.15
|
75.5 International units per liter (IU/L)
Standard Deviation 24.29
|
75.6 International units per liter (IU/L)
Standard Deviation 25.64
|
74.6 International units per liter (IU/L)
Standard Deviation 23.85
|
75.3 International units per liter (IU/L)
Standard Deviation 22.69
|
|
Assessment of Clinical Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT)
GGT, 2 5Hours 30 minutes
|
29.5 International units per liter (IU/L)
Standard Deviation 25.87
|
27.7 International units per liter (IU/L)
Standard Deviation 20.81
|
32.9 International units per liter (IU/L)
Standard Deviation 29.08
|
32.8 International units per liter (IU/L)
Standard Deviation 38.13
|
31.0 International units per liter (IU/L)
Standard Deviation 31.83
|
|
Assessment of Clinical Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT)
ALP, 25 Hours 30 minutes
|
75.3 International units per liter (IU/L)
Standard Deviation 23.26
|
75.7 International units per liter (IU/L)
Standard Deviation 23.75
|
76.9 International units per liter (IU/L)
Standard Deviation 27.15
|
75.2 International units per liter (IU/L)
Standard Deviation 23.71
|
75.8 International units per liter (IU/L)
Standard Deviation 25.73
|
|
Assessment of Clinical Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT)
ALT, Pre dose 1
|
30.7 International units per liter (IU/L)
Standard Deviation 19.09
|
30.1 International units per liter (IU/L)
Standard Deviation 17.66
|
31.2 International units per liter (IU/L)
Standard Deviation 18.97
|
32.2 International units per liter (IU/L)
Standard Deviation 26.62
|
39.6 International units per liter (IU/L)
Standard Deviation 71.33
|
|
Assessment of Clinical Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT)
ALT, 25 Hours 30 minutes
|
31.7 International units per liter (IU/L)
Standard Deviation 20.04
|
29.6 International units per liter (IU/L)
Standard Deviation 16.08
|
32.4 International units per liter (IU/L)
Standard Deviation 19.49
|
31.4 International units per liter (IU/L)
Standard Deviation 23.34
|
38.5 International units per liter (IU/L)
Standard Deviation 66.01
|
|
Assessment of Clinical Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT)
AST, Pre dose 1
|
24.5 International units per liter (IU/L)
Standard Deviation 13.29
|
24.0 International units per liter (IU/L)
Standard Deviation 10.26
|
25.4 International units per liter (IU/L)
Standard Deviation 14.81
|
24.6 International units per liter (IU/L)
Standard Deviation 11.42
|
27.3 International units per liter (IU/L)
Standard Deviation 31.46
|
|
Assessment of Clinical Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT)
AST, 25 Hours 30 minutes
|
24.0 International units per liter (IU/L)
Standard Deviation 10.14
|
23.3 International units per liter (IU/L)
Standard Deviation 8.82
|
27.3 International units per liter (IU/L)
Standard Deviation 19.39
|
23.9 International units per liter (IU/L)
Standard Deviation 9.72
|
26.9 International units per liter (IU/L)
Standard Deviation 31.33
|
|
Assessment of Clinical Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT)
GGT, Pre dose 1
|
29.8 International units per liter (IU/L)
Standard Deviation 29.45
|
28.1 International units per liter (IU/L)
Standard Deviation 21.98
|
31.5 International units per liter (IU/L)
Standard Deviation 27.08
|
32.8 International units per liter (IU/L)
Standard Deviation 39.54
|
30.3 International units per liter (IU/L)
Standard Deviation 30.77
|
SECONDARY outcome
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment periodPopulation: All Subjects Population. Only those participants available at the indicated time points were analyzed.
Blood samples were collected for the assessment of clinical chemistry parameters for direct bilirubin, total bilirubin and creatinine at pre dose and 25 hours and 30 minutes. Participants had to fast for at least 8 hours prior to visit. During treatment periods, fasting continued until a light meal was allowed 1 hour post dose.
Outcome measures
| Measure |
Placebo
n=44 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=45 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=47 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=45 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=45 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Assessment of Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin, Creatinine
Direct Bilirubin, Pre dose 1
|
2.361 Micromoles per liter (µmol/L)
Standard Deviation 1.8484
|
2.332 Micromoles per liter (µmol/L)
Standard Deviation 1.4326
|
2.230 Micromoles per liter (µmol/L)
Standard Deviation 1.8336
|
2.318 Micromoles per liter (µmol/L)
Standard Deviation 1.6769
|
2.280 Micromoles per liter (µmol/L)
Standard Deviation 2.1874
|
|
Assessment of Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin, Creatinine
Total Bilirubin, Pre dose 1
|
10.804 Micromoles per liter (µmol/L)
Standard Deviation 5.6386
|
11.348 Micromoles per liter (µmol/L)
Standard Deviation 5.0173
|
11.060 Micromoles per liter (µmol/L)
Standard Deviation 5.6473
|
11.438 Micromoles per liter (µmol/L)
Standard Deviation 5.8652
|
11.134 Micromoles per liter (µmol/L)
Standard Deviation 7.3966
|
|
Assessment of Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin, Creatinine
Total Bilirubin, 25 Hours 30 minutes
|
10.737 Micromoles per liter (µmol/L)
Standard Deviation 5.3078
|
10.412 Micromoles per liter (µmol/L)
Standard Deviation 4.8479
|
11.388 Micromoles per liter (µmol/L)
Standard Deviation 6.1270
|
10.982 Micromoles per liter (µmol/L)
Standard Deviation 5.8387
|
10.906 Micromoles per liter (µmol/L)
Standard Deviation 6.4426
|
|
Assessment of Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin, Creatinine
Creatinine, 25 Hours 30 minutes
|
85.83023 Micromoles per liter (µmol/L)
Standard Deviation 14.40704
|
86.71058 Micromoles per liter (µmol/L)
Standard Deviation 14.11612
|
87.91098 Micromoles per liter (µmol/L)
Standard Deviation 13.81935
|
87.57493 Micromoles per liter (µmol/L)
Standard Deviation 13.41632
|
87.57493 Micromoles per liter (µmol/L)
Standard Deviation 14.84895
|
|
Assessment of Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin, Creatinine
Direct Bilirubin, 25 Hours 30 minute
|
2.443 Micromoles per liter (µmol/L)
Standard Deviation 1.8938
|
2.204 Micromoles per liter (µmol/L)
Standard Deviation 1.2952
|
2.453 Micromoles per liter (µmol/L)
Standard Deviation 2.3266
|
2.584 Micromoles per liter (µmol/L)
Standard Deviation 1.8454
|
2.242 Micromoles per liter (µmol/L)
Standard Deviation 1.9230
|
|
Assessment of Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin, Creatinine
Creatinine, Pre dose 1
|
83.96594 Micromoles per liter (µmol/L)
Standard Deviation 18.34701
|
87.93791 Micromoles per liter (µmol/L)
Standard Deviation 20.15153
|
86.23702 Micromoles per liter (µmol/L)
Standard Deviation 13.21355
|
86.80880 Micromoles per liter (µmol/L)
Standard Deviation 13.90414
|
85.96409 Micromoles per liter (µmol/L)
Standard Deviation 14.50499
|
SECONDARY outcome
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment periodPopulation: All Subjects Population. Only those participants with data available at the indicated time points were analyzed.
Blood samples were collected for the assessment of clinical chemistry parameters for calcium, chloride, glucose, potassium, sodium and urea/BUN at pre dose and 25 hours and 30 minutes post dose. Participants had to fast for at least 8 hours prior to visit. Participants fasted for glucose blood sample. During treatment periods, fasting continued until a light meal was allowed 1 hour post dose.
Outcome measures
| Measure |
Placebo
n=44 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=45 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=47 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=45 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=45 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Assessment of Clinical Chemistry Parameters: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN)
Calcium, Pre dose 1
|
2.35494 Millimole per liter (mmol/L)
Standard Deviation 0.112125
|
2.36061 Millimole per liter (mmol/L)
Standard Deviation 0.107377
|
2.35910 Millimole per liter (mmol/L)
Standard Deviation 0.112041
|
2.35417 Millimole per liter (mmol/L)
Standard Deviation 0.109681
|
2.35084 Millimole per liter (mmol/L)
Standard Deviation 0.108088
|
|
Assessment of Clinical Chemistry Parameters: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN)
Calcium, 25 Hours 30 minutes
|
2.37605 Millimole per liter (mmol/L)
Standard Deviation 0.105831
|
2.38300 Millimole per liter (mmol/L)
Standard Deviation 0.110640
|
2.39308 Millimole per liter (mmol/L)
Standard Deviation 0.096186
|
2.38078 Millimole per liter (mmol/L)
Standard Deviation 0.091593
|
2.37136 Millimole per liter (mmol/L)
Standard Deviation 0.093348
|
|
Assessment of Clinical Chemistry Parameters: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN)
Chloride, Pre dose 1
|
105.2 Millimole per liter (mmol/L)
Standard Deviation 1.92
|
105.1 Millimole per liter (mmol/L)
Standard Deviation 2.04
|
105.2 Millimole per liter (mmol/L)
Standard Deviation 2.07
|
105.0 Millimole per liter (mmol/L)
Standard Deviation 2.34
|
105.1 Millimole per liter (mmol/L)
Standard Deviation 2.42
|
|
Assessment of Clinical Chemistry Parameters: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN)
Potassium, Pre dose 1
|
4.40 Millimole per liter (mmol/L)
Standard Deviation 0.328
|
4.40 Millimole per liter (mmol/L)
Standard Deviation 0.456
|
4.31 Millimole per liter (mmol/L)
Standard Deviation 0.386
|
4.29 Millimole per liter (mmol/L)
Standard Deviation 0.320
|
4.36 Millimole per liter (mmol/L)
Standard Deviation 0.422
|
|
Assessment of Clinical Chemistry Parameters: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN)
Urea/BUN, Pre dose 1
|
5.8175 Millimole per liter (mmol/L)
Standard Deviation 1.32593
|
5.6390 Millimole per liter (mmol/L)
Standard Deviation 1.56766
|
5.7652 Millimole per liter (mmol/L)
Standard Deviation 1.24779
|
5.7120 Millimole per liter (mmol/L)
Standard Deviation 1.25759
|
5.6565 Millimole per liter (mmol/L)
Standard Deviation 1.31601
|
|
Assessment of Clinical Chemistry Parameters: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN)
Urea/BUN, 25 Hours 30 minutes
|
5.6539 Millimole per liter (mmol/L)
Standard Deviation 1.12605
|
5.5930 Millimole per liter (mmol/L)
Standard Deviation 1.11343
|
5.7424 Millimole per liter (mmol/L)
Standard Deviation 1.06537
|
5.8786 Millimole per liter (mmol/L)
Standard Deviation 1.09666
|
5.5771 Millimole per liter (mmol/L)
Standard Deviation 1.30126
|
|
Assessment of Clinical Chemistry Parameters: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN)
Chloride, 25 Hours 30 minutes
|
104.7 Millimole per liter (mmol/L)
Standard Deviation 2.36
|
105.4 Millimole per liter (mmol/L)
Standard Deviation 1.85
|
105.2 Millimole per liter (mmol/L)
Standard Deviation 2.28
|
104.8 Millimole per liter (mmol/L)
Standard Deviation 2.05
|
105.5 Millimole per liter (mmol/L)
Standard Deviation 2.29
|
|
Assessment of Clinical Chemistry Parameters: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN)
Glucose, Pre dose 1
|
4.80162 Millimole per liter (mmol/L)
Standard Deviation 0.783522
|
4.73601 Millimole per liter (mmol/L)
Standard Deviation 0.804663
|
4.97937 Millimole per liter (mmol/L)
Standard Deviation 0.843434
|
4.88735 Millimole per liter (mmol/L)
Standard Deviation 0.770075
|
4.95273 Millimole per liter (mmol/L)
Standard Deviation 0.768704
|
|
Assessment of Clinical Chemistry Parameters: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN)
Glucose, 25 Hours 30 minutes
|
4.99203 Millimole per liter (mmol/L)
Standard Deviation 0.859137
|
4.96753 Millimole per liter (mmol/L)
Standard Deviation 0.892300
|
4.73370 Millimole per liter (mmol/L)
Standard Deviation 0.824460
|
5.02921 Millimole per liter (mmol/L)
Standard Deviation 1.004730
|
5.07855 Millimole per liter (mmol/L)
Standard Deviation 1.164605
|
|
Assessment of Clinical Chemistry Parameters: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN)
Potassium, 25 Hours 30 minutes
|
4.43 Millimole per liter (mmol/L)
Standard Deviation 0.342
|
4.51 Millimole per liter (mmol/L)
Standard Deviation 0.362
|
4.44 Millimole per liter (mmol/L)
Standard Deviation 0.374
|
4.44 Millimole per liter (mmol/L)
Standard Deviation 0.322
|
4.50 Millimole per liter (mmol/L)
Standard Deviation 0.333
|
|
Assessment of Clinical Chemistry Parameters: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN)
Sodium, Pre dose 1
|
140.6 Millimole per liter (mmol/L)
Standard Deviation 2.16
|
140.9 Millimole per liter (mmol/L)
Standard Deviation 2.23
|
140.1 Millimole per liter (mmol/L)
Standard Deviation 2.17
|
139.9 Millimole per liter (mmol/L)
Standard Deviation 2.37
|
140.2 Millimole per liter (mmol/L)
Standard Deviation 1.87
|
|
Assessment of Clinical Chemistry Parameters: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN)
Sodium, 25 Hours 30 minutes
|
140.0 Millimole per liter (mmol/L)
Standard Deviation 2.13
|
140.6 Millimole per liter (mmol/L)
Standard Deviation 2.34
|
140.3 Millimole per liter (mmol/L)
Standard Deviation 2.18
|
139.6 Millimole per liter (mmol/L)
Standard Deviation 2.03
|
140.2 Millimole per liter (mmol/L)
Standard Deviation 2.14
|
SECONDARY outcome
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment periodPopulation: All Subjects Population. Only those participants with data available at the indicated time points were analyzed.
Blood samples were collected for the assessment of hematology parameters for basophils, eosinophils, lymphocytes, monocytes, TN, platelet count, WBC at pre dose and 25 hours and 30 minutes post dose. Participants had to fast for at least 8 hours prior to visit. During treatment periods, fasting continued until a light meal was allowed 1 hour post dose.
Outcome measures
| Measure |
Placebo
n=44 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=45 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=47 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=45 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=45 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Assessment of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (TN) (ANC - Absolute Neutrophil Count), Platelet Count, White Blood Cell Count (WBC)
Basophils, Pre dose 1
|
0.0306 Cells x 10^9 per liter
Standard Deviation 0.01326
|
0.0281 Cells x 10^9 per liter
Standard Deviation 0.01065
|
0.0276 Cells x 10^9 per liter
Standard Deviation 0.01133
|
0.0316 Cells x 10^9 per liter
Standard Deviation 0.02112
|
0.0298 Cells x 10^9 per liter
Standard Deviation 0.01261
|
|
Assessment of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (TN) (ANC - Absolute Neutrophil Count), Platelet Count, White Blood Cell Count (WBC)
Basophils, 25 Hours 30 minutes
|
0.0242 Cells x 10^9 per liter
Standard Deviation 0.01064
|
0.0303 Cells x 10^9 per liter
Standard Deviation 0.00968
|
0.0333 Cells x 10^9 per liter
Standard Deviation 0.01805
|
0.0282 Cells x 10^9 per liter
Standard Deviation 0.00944
|
0.0252 Cells x 10^9 per liter
Standard Deviation 0.01171
|
|
Assessment of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (TN) (ANC - Absolute Neutrophil Count), Platelet Count, White Blood Cell Count (WBC)
Eosinophils, Pre dose 1
|
0.2638 Cells x 10^9 per liter
Standard Deviation 0.21459
|
0.2574 Cells x 10^9 per liter
Standard Deviation 0.20600
|
0.2392 Cells x 10^9 per liter
Standard Deviation 0.15458
|
0.2563 Cells x 10^9 per liter
Standard Deviation 0.21963
|
0.2166 Cells x 10^9 per liter
Standard Deviation 0.11200
|
|
Assessment of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (TN) (ANC - Absolute Neutrophil Count), Platelet Count, White Blood Cell Count (WBC)
Lymphocyte, Pre dose 1
|
2.2320 Cells x 10^9 per liter
Standard Deviation 0.62143
|
2.2139 Cells x 10^9 per liter
Standard Deviation 0.56983
|
2.3156 Cells x 10^9 per liter
Standard Deviation 0.56904
|
2.3581 Cells x 10^9 per liter
Standard Deviation 0.66985
|
2.1852 Cells x 10^9 per liter
Standard Deviation 0.69204
|
|
Assessment of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (TN) (ANC - Absolute Neutrophil Count), Platelet Count, White Blood Cell Count (WBC)
Lymphocyte, 25 Hours 30 minutes
|
1.8281 Cells x 10^9 per liter
Standard Deviation 0.47068
|
1.8847 Cells x 10^9 per liter
Standard Deviation 0.55807
|
1.9052 Cells x 10^9 per liter
Standard Deviation 0.48399
|
1.8809 Cells x 10^9 per liter
Standard Deviation 0.49456
|
1.8677 Cells x 10^9 per liter
Standard Deviation 0.62646
|
|
Assessment of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (TN) (ANC - Absolute Neutrophil Count), Platelet Count, White Blood Cell Count (WBC)
TN, Pre dose 1
|
3.4340 Cells x 10^9 per liter
Standard Deviation 0.98614
|
3.3645 Cells x 10^9 per liter
Standard Deviation 0.92934
|
3.4151 Cells x 10^9 per liter
Standard Deviation 0.96375
|
3.6047 Cells x 10^9 per liter
Standard Deviation 1.19442
|
3.5448 Cells x 10^9 per liter
Standard Deviation 1.05765
|
|
Assessment of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (TN) (ANC - Absolute Neutrophil Count), Platelet Count, White Blood Cell Count (WBC)
Plateletcount, Pre dose 1
|
241.8 Cells x 10^9 per liter
Standard Deviation 58.19
|
238.0 Cells x 10^9 per liter
Standard Deviation 51.85
|
243.0 Cells x 10^9 per liter
Standard Deviation 47.46
|
240.1 Cells x 10^9 per liter
Standard Deviation 50.26
|
238.4 Cells x 10^9 per liter
Standard Deviation 49.15
|
|
Assessment of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (TN) (ANC - Absolute Neutrophil Count), Platelet Count, White Blood Cell Count (WBC)
WBC count, 25 Hours 30 minutes
|
6.56 Cells x 10^9 per liter
Standard Deviation 1.708
|
6.56 Cells x 10^9 per liter
Standard Deviation 1.434
|
6.67 Cells x 10^9 per liter
Standard Deviation 1.605
|
6.75 Cells x 10^9 per liter
Standard Deviation 1.650
|
6.39 Cells x 10^9 per liter
Standard Deviation 1.681
|
|
Assessment of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (TN) (ANC - Absolute Neutrophil Count), Platelet Count, White Blood Cell Count (WBC)
Eosinophils, 25 Hours 30 minutes
|
0.2241 Cells x 10^9 per liter
Standard Deviation 0.15104
|
0.2610 Cells x 10^9 per liter
Standard Deviation 0.18803
|
0.2431 Cells x 10^9 per liter
Standard Deviation 0.15657
|
0.2271 Cells x 10^9 per liter
Standard Deviation 0.18567
|
0.1974 Cells x 10^9 per liter
Standard Deviation 0.10502
|
|
Assessment of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (TN) (ANC - Absolute Neutrophil Count), Platelet Count, White Blood Cell Count (WBC)
Monocyte, Pre dose 1
|
0.4673 Cells x 10^9 per liter
Standard Deviation 0.18438
|
0.4366 Cells x 10^9 per liter
Standard Deviation 0.11641
|
0.4799 Cells x 10^9 per liter
Standard Deviation 0.10725
|
0.4671 Cells x 10^9 per liter
Standard Deviation 0.11368
|
0.4307 Cells x 10^9 per liter
Standard Deviation 0.12690
|
|
Assessment of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (TN) (ANC - Absolute Neutrophil Count), Platelet Count, White Blood Cell Count (WBC)
Monocyte, 25 Hours 30 minutes
|
0.3912 Cells x 10^9 per liter
Standard Deviation 0.09575
|
0.4289 Cells x 10^9 per liter
Standard Deviation 0.12575
|
0.4489 Cells x 10^9 per liter
Standard Deviation 0.13018
|
0.4190 Cells x 10^9 per liter
Standard Deviation 0.11797
|
0.4084 Cells x 10^9 per liter
Standard Deviation 0.15112
|
|
Assessment of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (TN) (ANC - Absolute Neutrophil Count), Platelet Count, White Blood Cell Count (WBC)
TN, 25 Hours 30 minutes
|
3.6062 Cells x 10^9 per liter
Standard Deviation 1.16759
|
3.6962 Cells x 10^9 per liter
Standard Deviation 0.92202
|
3.7720 Cells x 10^9 per liter
Standard Deviation 1.08800
|
3.7813 Cells x 10^9 per liter
Standard Deviation 1.26257
|
3.5289 Cells x 10^9 per liter
Standard Deviation 1.13473
|
|
Assessment of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (TN) (ANC - Absolute Neutrophil Count), Platelet Count, White Blood Cell Count (WBC)
Plateletcount, 25 Hours 30 minutes
|
242.7 Cells x 10^9 per liter
Standard Deviation 55.97
|
239.0 Cells x 10^9 per liter
Standard Deviation 48.39
|
243.3 Cells x 10^9 per liter
Standard Deviation 46.73
|
240.5 Cells x 10^9 per liter
Standard Deviation 50.51
|
238.0 Cells x 10^9 per liter
Standard Deviation 52.59
|
|
Assessment of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (TN) (ANC - Absolute Neutrophil Count), Platelet Count, White Blood Cell Count (WBC)
WBC count, Pre dose 1
|
6.69 Cells x 10^9 per liter
Standard Deviation 1.689
|
6.58 Cells x 10^9 per liter
Standard Deviation 1.638
|
6.77 Cells x 10^9 per liter
Standard Deviation 1.627
|
6.79 Cells x 10^9 per liter
Standard Deviation 1.726
|
6.50 Cells x 10^9 per liter
Standard Deviation 1.465
|
SECONDARY outcome
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment periodPopulation: All Subjects Population. Only those participants with data available at the indicated time points were analyzed.
Blood samples were collected for the assessment of hematology parameters for hemoglobin and MCHC at pre dose and 25 hours and 30 minutes post dose. Participants had to fast for at least 8 hours prior to visit. During treatment periods, fasting continued until a light meal was allowed 1 hour post dose.
Outcome measures
| Measure |
Placebo
n=44 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=45 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=47 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=45 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=45 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Assessment of Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC)
Hemoglobin, Pre dose 1
|
152.0 G/L
Standard Deviation 13.75
|
152.9 G/L
Standard Deviation 13.00
|
151.3 G/L
Standard Deviation 14.44
|
152.4 G/L
Standard Deviation 12.95
|
151.3 G/L
Standard Deviation 14.58
|
|
Assessment of Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC)
Hemoglobin, 25 hours 30 minutes
|
151.1 G/L
Standard Deviation 12.84
|
151.9 G/L
Standard Deviation 13.80
|
157.8 G/L
Standard Deviation 45.11
|
151.3 G/L
Standard Deviation 12.93
|
151.2 G/L
Standard Deviation 13.41
|
|
Assessment of Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC)
MCHC, Pre dose 1
|
340.5 G/L
Standard Deviation 8.55
|
339.3 G/L
Standard Deviation 8.77
|
341.2 G/L
Standard Deviation 8.35
|
340.0 G/L
Standard Deviation 8.88
|
338.6 G/L
Standard Deviation 9.40
|
|
Assessment of Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC)
MCHC, 25 hours 30 minutes
|
340.2 G/L
Standard Deviation 9.14
|
341.1 G/L
Standard Deviation 7.43
|
340.4 G/L
Standard Deviation 9.30
|
340.4 G/L
Standard Deviation 9.05
|
339.8 G/L
Standard Deviation 9.96
|
SECONDARY outcome
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment periodPopulation: All Subjects Population. Only those participants with data available at the indicated time points were analyzed.
Blood samples were collected for the assessment of hematology parameters for hematocrit at pre dose and 25 hours and 30 minutes post dose. Participants had to fast for at least 8 hours prior to visit. During treatment periods, fasting continued until a light meal was allowed 1 hour post dose.
Outcome measures
| Measure |
Placebo
n=44 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=45 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=47 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=45 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=45 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Assessment of Hematology Parameters: Hematocrit
Pre dose 1
|
0.4463 Ratio
Standard Deviation 0.03720
|
0.4503 Ratio
Standard Deviation 0.03423
|
0.4431 Ratio
Standard Deviation 0.03885
|
0.4480 Ratio
Standard Deviation 0.03265
|
0.4465 Ratio
Standard Deviation 0.03864
|
|
Assessment of Hematology Parameters: Hematocrit
25 Hours 30 Minutes
|
0.4440 Ratio
Standard Deviation 0.03186
|
0.4451 Ratio
Standard Deviation 0.03765
|
0.4453 Ratio
Standard Deviation 0.03375
|
0.4442 Ratio
Standard Deviation 0.03244
|
0.4448 Ratio
Standard Deviation 0.03628
|
SECONDARY outcome
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment periodPopulation: All Subjects Population. Only those participants with data available at the indicated time points were analyzed
Blood samples were collected for the assessment of hematology parameter for MCH at pre dose and 25 hours and 30 minutes post dose. Participants had to fast for at least 8 hours prior to visit. During treatment periods, fasting continued until a light meal was allowed 1 hour post dose.
Outcome measures
| Measure |
Placebo
n=44 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=45 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=47 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=45 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=45 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Assessment of Hematology Parameters: Mean Corpuscle Hemoglobin (MCH)
25 Hours 30 Minutes
|
30.19 Picograms
Standard Deviation 2.157
|
30.20 Picograms
Standard Deviation 2.050
|
30.27 Picograms
Standard Deviation 2.076
|
30.18 Picograms
Standard Deviation 2.050
|
30.32 Picograms
Standard Deviation 2.102
|
|
Assessment of Hematology Parameters: Mean Corpuscle Hemoglobin (MCH)
Pre dose 1
|
30.27 Picograms
Standard Deviation 2.078
|
30.14 Picograms
Standard Deviation 2.122
|
30.30 Picograms
Standard Deviation 2.032
|
30.25 Picograms
Standard Deviation 2.024
|
30.14 Picograms
Standard Deviation 2.008
|
SECONDARY outcome
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment periodPopulation: All Subjects Population. Only those participants with data available at the indicated time points were analyzed.
Blood samples were collected for the assessment of hematology parameter for MCV at pre dose and 25 hours and 30 minutes post dose. Participants had to fast for at least 8 hours prior to visit. During treatment periods, fasting continued until a light meal was allowed 1 hour post dose.
Outcome measures
| Measure |
Placebo
n=44 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=45 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=47 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=45 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=45 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Assessment of Hematology Parameters: Mean Corpuscle Volume (MCV)
Pre dose 1
|
88.85 Femtoliter
Standard Deviation 5.589
|
88.75 Femtoliter
Standard Deviation 5.500
|
88.80 Femtoliter
Standard Deviation 5.464
|
88.96 Femtoliter
Standard Deviation 5.673
|
89.06 Femtoliter
Standard Deviation 5.703
|
|
Assessment of Hematology Parameters: Mean Corpuscle Volume (MCV)
25 Hours 30 Minutes
|
88.74 Femtoliter
Standard Deviation 6.116
|
88.57 Femtoliter
Standard Deviation 5.612
|
88.89 Femtoliter
Standard Deviation 5.696
|
88.69 Femtoliter
Standard Deviation 5.625
|
89.23 Femtoliter
Standard Deviation 5.730
|
SECONDARY outcome
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment periodPopulation: All Subjects Population. Only those participants with data available at the indicated time points were analyzed.
Blood samples were collected for the assessment of hematology parameter for RBC at pre dose and 25 hours and 30 minutes post dose. Participants had to fast for at least 8 hours prior to visit. During treatment periods, fasting continued until a light meal was allowed 1 hour post dose.
Outcome measures
| Measure |
Placebo
n=44 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=45 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=47 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=45 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=45 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Assessment of Hematology Parameters: Red Blood Cell Count (RBC)
Pre dose 1
|
5.038 Cells x 10^12 per liter
Standard Deviation 0.4699
|
5.086 Cells x 10^12 per liter
Standard Deviation 0.4255
|
5.005 Cells x 10^12 per liter
Standard Deviation 0.4853
|
5.050 Cells x 10^12 per liter
Standard Deviation 0.4044
|
5.030 Cells x 10^12 per liter
Standard Deviation 0.4756
|
|
Assessment of Hematology Parameters: Red Blood Cell Count (RBC)
25 Hours 30 Minutes
|
5.018 Cells x 10^12 per liter
Standard Deviation 0.3819
|
5.039 Cells x 10^12 per liter
Standard Deviation 0.4533
|
5.023 Cells x 10^12 per liter
Standard Deviation 0.4253
|
5.025 Cells x 10^12 per liter
Standard Deviation 0.4112
|
4.998 Cells x 10^12 per liter
Standard Deviation 0.4557
|
SECONDARY outcome
Timeframe: Up to follow up (7 to 21 days) following last dosePopulation: All Subjects Population.
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An 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, is a congenital anomaly/birth defect and medically significant.
Outcome measures
| Measure |
Placebo
n=44 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=45 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=47 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=45 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=45 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any SAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Any AEs
|
4 Participants
|
4 Participants
|
4 Participants
|
0 Participants
|
4 Participants
|
SECONDARY outcome
Timeframe: Baseline (pre dose) up to 24 Hours post dose of each treatment periodPopulation: Pharmacodynamics (PD) Population was defined as participants in the 'All Subjects' Population for whom a PD sample (blood or urine) was obtained and analyzed. Only those participants available at the indicated time points were analyzed.
Analysis LTB4 levels in the blood samples indicated the extent of LTB4 inhibition following administration of GSK2190915 compared to Baseline. Baseline was the pre dose value. Change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Outcome measures
| Measure |
Placebo
n=8 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=9 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=10 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=9 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=9 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Percentage Change From Baseline in Blood Leukotriene B4 (LTB4)
9.5 Hours, Pre exercise
|
-14.82 Percent change
Interval -74.6 to 239.4
|
-23.43 Percent change
Interval -93.4 to 31.1
|
-87.74 Percent change
Interval -98.4 to -23.0
|
-96.53 Percent change
Interval -99.4 to -45.2
|
-99.78 Percent change
Interval -100.0 to -95.0
|
|
Percentage Change From Baseline in Blood Leukotriene B4 (LTB4)
2 Hours, Pre exercise
|
-37.32 Percent change
Interval -57.8 to 241.4
|
-29.32 Percent change
Interval -78.4 to 125.3
|
-87.65 Percent change
Interval -99.6 to 78.9
|
-97.98 Percent change
Interval -99.7 to 25.9
|
-98.43 Percent change
Interval -100.0 to -55.9
|
|
Percentage Change From Baseline in Blood Leukotriene B4 (LTB4)
24 Hours, Pre exercise
|
12.59 Percent change
Interval -57.2 to 235.1
|
-9.56 Percent change
Interval -83.3 to 167.9
|
-84.49 Percent change
Interval -96.7 to -36.3
|
-70.00 Percent change
Interval -97.8 to 209.4
|
-98.75 Percent change
Interval -99.8 to -64.9
|
SECONDARY outcome
Timeframe: Baseline (pre dose) up to 24 Hours post dose of each treatment periodPopulation: PD Population. Only those participants available at the indicated time points were analyzed.
Analysis of LTE4 levels in the urine samples indicated the extent of LTE4 inhibition following administration of GSK2190915 compared to Baseline. Baseline was the pre dose value. Change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.
Outcome measures
| Measure |
Placebo
n=8 Participants
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
|
GSK2190915 10 mg
n=9 Participants
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 50 mg
n=10 Participants
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 100 mg
n=9 Participants
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
GSK2190915 200 mg
n=9 Participants
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
|
|---|---|---|---|---|---|
|
Percentage Change From Baseline in Urine Leukotriene E4 (LTE4)
9.5 Hours, 1 Hour 30 Minutes post dose
|
0.96 Percent change
Interval -49.0 to 88.5
|
-45.05 Percent change
Interval -89.3 to -15.9
|
-61.86 Percent change
Interval -86.6 to -0.3
|
-63.67 Percent change
Interval -83.5 to -42.1
|
-81.03 Percent change
Interval -94.4 to 5.8
|
|
Percentage Change From Baseline in Urine Leukotriene E4 (LTE4)
24 Hours, Pre exercise post dose
|
-14.04 Percent change
Interval -50.3 to 24.1
|
-29.26 Percent change
Interval -82.6 to 21.3
|
-70.37 Percent change
Interval -88.7 to 24.9
|
-72.55 Percent change
Interval -99.5 to -5.7
|
-77.07 Percent change
Interval -99.1 to -34.2
|
|
Percentage Change From Baseline in Urine Leukotriene E4 (LTE4)
2 Hours, Pre exercise
|
-0.30 Percent change
Interval -13.3 to 89.6
|
-19.68 Percent change
Interval -58.1 to 5.4
|
-12.58 Percent change
Interval -76.8 to 971.1
|
-9.71 Percent change
Interval -53.8 to 24.4
|
-12.29 Percent change
Interval -65.3 to 55.3
|
|
Percentage Change From Baseline in Urine Leukotriene E4 (LTE4)
2 Hours, 1 Hour 30 Minutes post dose
|
6.61 Percent change
Interval -49.0 to 83.6
|
-28.97 Percent change
Interval -84.4 to 1.4
|
-39.12 Percent change
Interval -81.9 to 920.7
|
-28.67 Percent change
Interval -71.0 to 18.3
|
-30.02 Percent change
Interval -85.6 to 53.8
|
|
Percentage Change From Baseline in Urine Leukotriene E4 (LTE4)
9.5 Hours, Pre exercise post dose
|
0.82 Percent change
Interval -42.4 to 37.9
|
-52.76 Percent change
Interval -86.0 to 0.3
|
-66.74 Percent change
Interval -86.4 to 629.8
|
-59.85 Percent change
Interval -98.2 to -23.1
|
-70.43 Percent change
Interval -87.7 to -27.3
|
SECONDARY outcome
Timeframe: Pre dose, 2 hours, 3.5 hours, 9.5 hours, 11 hours and 24 hours following exercise challenge of each treatment periodPopulation: PK Population was defined as participants in the 'All Subjects' Population for whom a PK sample was obtained and analyzed. Data was not collected for this outcome measure.
PK samples were supposed to be collected at 10 minutes prior to the exercise challenge at 2 hours, 9.5 hours and 24 hours.
Outcome measures
Outcome data not reported
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
GSK2190915 10 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
GSK2190915 50 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
GSK2190915 100 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
GSK2190915 200 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=44 participants at risk
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of the treatment period.
|
GSK2190915 10 mg
n=45 participants at risk
Eligible participants received single dose 10 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of the treatment period.
|
GSK2190915 50 mg
n=47 participants at risk
Eligible participants received single dose 50 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of the treatment period.
|
GSK2190915 100 mg
n=45 participants at risk
Eligible participants received single dose 100 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of the treatment period.
|
GSK2190915 200 mg
n=45 participants at risk
Eligible participants received single dose 200 mg GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of the treatment period.
|
|---|---|---|---|---|---|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/44 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
2.1%
1/47 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
|
Nervous system disorders
Dizziness
|
4.5%
2/44 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
2.2%
1/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
4.3%
2/47 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
|
Nervous system disorders
Headache
|
2.3%
1/44 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/47 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
4.4%
2/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
|
Nervous system disorders
Tension headache
|
0.00%
0/44 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/47 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
2.2%
1/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/44 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
2.2%
1/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/47 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.00%
0/44 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
2.1%
1/47 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
|
Gastrointestinal disorders
Diarrhoea
|
2.3%
1/44 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
2.2%
1/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/47 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
|
General disorders
Fatigue
|
0.00%
0/44 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
2.2%
1/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/47 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/44 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
2.1%
1/47 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/44 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
2.1%
1/47 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/44 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/47 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
2.2%
1/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/44 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
2.2%
1/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
2.1%
1/47 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
0.00%
0/45 • AEs were collected up to follow up (up to 7 to 21 days following last dose).
All Subjects Population was used.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
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