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A Clinical Trial to Test a Study Drug in Volunteers Who Develop Asthma Following Exercise

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00812929
Recruitment Status : Completed
First Posted : December 22, 2008
Results First Posted : September 19, 2017
Last Update Posted : September 19, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: Placebo
Drug: GSK2190915
Enrollment 47

Recruitment Details This was a Phase IIa multi-center study conducted in the United States from 02 December 2008 to 15 July 2009.
Pre-assignment Details 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.
Arm/Group Title P/A/D/B/C A/B/P/C/D B/C/A/D/P C/D/B/P/A D/P/C/A/B C/B/D/A/P D/C/P/B/A P/D/A/C/B A/P/B/D/C B/A/C/P/D
Hide Arm/Group Description 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. 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. 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. 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. 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. 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. 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. 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. 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. 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.
Period Title: Treatment Period 1
Started 5 4 5 4 5 5 5 5 4 5
Completed 5 4 5 4 5 5 5 5 4 5
Not Completed 0 0 0 0 0 0 0 0 0 0
Period Title: Washout Period 1 (7 Days)
Started 5 4 5 4 5 5 5 5 4 5
Completed 5 4 4 4 5 5 5 5 4 5
Not Completed 0 0 1 0 0 0 0 0 0 0
Reason Not Completed
Physician Decision             0             0             1             0             0             0             0             0             0             0
Period Title: Treatment Period 2
Started 5 4 4 4 5 5 5 5 4 5
Completed 5 4 4 4 5 5 5 5 4 5
Not Completed 0 0 0 0 0 0 0 0 0 0
Period Title: Washout Period 2 (7 Days)
Started 5 4 4 4 5 5 5 5 4 5
Completed 5 4 4 4 5 5 5 5 4 4
Not Completed 0 0 0 0 0 0 0 0 0 1
Reason Not Completed
Physician Decision             0             0             0             0             0             0             0             0             0             1
Period Title: Treatment Period 3
Started 5 4 4 4 5 5 5 5 4 4
Completed 5 4 4 4 5 5 5 5 4 4
Not Completed 0 0 0 0 0 0 0 0 0 0
Period Title: Washout Period 3 (7 Days)
Started 5 4 4 4 5 5 5 5 4 4
Completed 5 4 4 4 5 4 5 5 4 4
Not Completed 0 0 0 0 0 1 0 0 0 0
Reason Not Completed
Adverse Event             0             0             0             0             0             1             0             0             0             0
Period Title: Treatment Period 4
Started 5 4 4 4 5 4 5 5 4 4
Completed 5 4 4 4 5 4 5 5 4 4
Not Completed 0 0 0 0 0 0 0 0 0 0
Period Title: Washout Period 4 (7 Days)
Started 5 4 4 4 5 4 5 5 4 4
Completed 5 4 4 4 5 4 5 5 4 4
Not Completed 0 0 0 0 0 0 0 0 0 0
Period Title: Treatment Period 5
Started 5 4 4 4 5 4 5 5 4 4
Completed 5 4 4 4 5 4 5 5 4 4
Not Completed 0 0 0 0 0 0 0 0 0 0
Arm/Group Title Total
Hide Arm/Group Description 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.
Overall Number of Baseline Participants 47
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 47 participants
28.4  (8.57)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 47 participants
Female
6
  12.8%
Male
41
  87.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 47 participants
American Indian or Alaska Native
0
   0.0%
Asian
3
   6.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
6
  12.8%
White
38
  80.9%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
Title 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
Hide Description 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.
Time Frame Baseline (pre dose) and 60 minutes following the exercise challenge at 24 hours post dose of each treatment period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The ‘Efficacy Population’ was defined as all participants who received at least one dose of study medication and are not major protocol violators.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 milliliter (mL) of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 44 45 46 45 45
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
-7.61  (1.326) -6.33  (1.314) -7.09  (1.307) -7.28  (1.314) -5.09  (1.315)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 10 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.29
Confidence Interval (2-Sided) 95%
-1.56 to 4.13
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.440
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 50 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
-2.32 to 3.37
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.440
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
-2.52 to 3.18
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.441
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 200 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.53
Confidence Interval (2-Sided) 95%
-0.31 to 5.37
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.438
Estimation Comments [Not Specified]
2.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline (pre dose) and 60 minutes following the exercise challenge at 2 and 9.5 hours post dose of each treatment period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 44 45 46 45 45
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
2 Hours -15.55  (1.437) -13.04  (1.424) -12.95  (1.416) -12.76  (1.424) -9.25  (1.425)
9.5 Hours -8.45  (1.222) -8.33  (1.212) -7.69  (1.206) -4.96  (1.213) -6.18  (1.213)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 10 mg
Comments 2 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.52
Confidence Interval (2-Sided) 95%
-0.72 to 5.75
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.638
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 10 mg
Comments 9.5 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.12
Confidence Interval (2-Sided) 95%
-2.34 to 2.58
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.247
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 50 mg
Comments 2 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.60
Confidence Interval (2-Sided) 95%
-0.64 to 5.84
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.637
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 50 mg
Comments 9.5 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
-1.70 to 3.22
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.247
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 100 mg
Comments 2 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.79
Confidence Interval (2-Sided) 95%
-0.45 to 6.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.639
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 100 mg
Comments 9.5 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.49
Confidence Interval (2-Sided) 95%
1.02 to 5.95
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.248
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 200 mg
Comments 2 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 6.30
Confidence Interval (2-Sided) 95%
3.06 to 9.54
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.637
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 200 mg
Comments 9.5 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.27
Confidence Interval (2-Sided) 95%
-0.19 to 4.73
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.245
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Weighted Mean (WM) for FEV1 Percentage Change From Baseline Recorded During 0 to 60 Minutes Following Exercise Challenge (FEV1 WM0-60)
Hide Description 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.
Time Frame Baseline (pre dose) and 0 to 60 minutes following exercise challenge at 2, 9.5 and 24 hours post dose of each treatment period.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 44 45 46 45 45
Least Squares Mean (Standard Error)
Unit of Measure: Percent change
2 Hours -5.20  (0.936) -4.26  (0.926) -4.08  (0.920) -3.69  (0.926) -2.04  (0.927)
9.5 Hours -2.43  (0.757) -2.36  (0.750) -1.21  (0.745) 0.87  (0.750) -0.32  (0.750)
24 Hours -0.25  (0.755) 0.65  (0.747) -0.08  (0.742) -0.35  (0.747) 1.46  (0.748)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 10 mg
Comments 2 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
-1.37 to 3.25
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.170
Estimation Comments Estimates and 95% confidence intervals for treatment difference between each active dose and placebo for each challenge time point were calculated.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 10 mg
Comments 9.5 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
-1.66 to 1.80
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.878
Estimation Comments Estimates and 95% confidence intervals for treatment difference between each active dose and placebo for each challenge time point were calculated.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 10 mg
Comments 24 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
-0.82 to 2.63
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.873
Estimation Comments Estimates and 95% confidence intervals for treatment difference between each active dose and placebo for each challenge time point were calculated.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 50 mg
Comments 2 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
-1.19 to 3.43
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.169
Estimation Comments Estimates and 95% confidence intervals for treatment difference between each active dose and placebo for each challenge time point were calculated.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 50 mg
Comments 9.5 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.22
Confidence Interval (2-Sided) 95%
-0.51 to 2.95
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.878
Estimation Comments Estimates and 95% confidence intervals for treatment difference between each active dose and placebo for each challenge time point were calculated.
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 50 mg
Comments 24 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.18
Confidence Interval (2-Sided) 95%
-1.55 to 1.90
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.873
Estimation Comments Estimates and 95% confidence intervals for treatment difference between each active dose and placebo for each challenge time point were calculated.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 100 mg
Comments 2 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.51
Confidence Interval (2-Sided) 95%
-0.80 to 3.82
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.171
Estimation Comments Estimates and 95% confidence intervals for treatment difference between each active dose and placebo for each challenge time point were calculated.
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 100 mg
Comments 9.5 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.30
Confidence Interval (2-Sided) 95%
1.57 to 5.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.879
Estimation Comments Estimates and 95% confidence intervals for treatment difference between each active dose and placebo for each challenge time point were calculated.
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 100 mg
Comments 24 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.10
Confidence Interval (2-Sided) 95%
-1.83 to 1.62
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.874
Estimation Comments Estimates and 95% confidence intervals for treatment difference between each active dose and placebo for each challenge time point were calculated.
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 200 mg
Comments 2 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 3.17
Confidence Interval (2-Sided) 95%
0.86 to 5.48
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.169
Estimation Comments Estimates and 95% confidence intervals for treatment difference between each active dose and placebo for each challenge time point were calculated.
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 200 mg
Comments 9.5 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.11
Confidence Interval (2-Sided) 95%
0.38 to 3.84
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.877
Estimation Comments Estimates and 95% confidence intervals for treatment difference between each active dose and placebo for each challenge time point were calculated.
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 200 mg
Comments 24 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.72
Confidence Interval (2-Sided) 95%
-0.00 to 3.44
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.872
Estimation Comments Estimates and 95% confidence intervals for treatment difference between each active dose and placebo for each challenge time point were calculated.
4.Secondary Outcome
Title Time to FEV1 Recovery to Within 5 Percent of Baseline Following Exercise Challenge
Hide Description 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.
Time Frame 0 to 60 minutes following exercise challenge at 2, 9.5 and 24 hours post dose of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 44 45 46 45 45
Median (95% Confidence Interval)
Unit of Measure: Minutes
2 Hours
24.5
(15.0 to 36.0)
15.0
(10.0 to 30.0)
18.0
(5.0 to 35.0)
10.0
(5.0 to 16.0)
5.0
(0.0 to 12.0)
9.5 Hours
5.0
(0.0 to 18.0)
9.0
(0.0 to 25.0)
5.0
(0.0 to 10.0)
0.0
(0.0 to 5.0)
0.0
(0.0 to 5.0)
24 Hours
5.0
(0.0 to 16.0)
0.0
(0.0 to 5.0)
2.5
(0.0 to 6.0)
5.0
(0.0 to 5.0)
0.0
(0.0 to 5.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 10 mg
Comments 2 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.25
Confidence Interval (2-Sided) 95%
0.71 to 2.21
Estimation Comments Hazard ratio = ratio of likelihood of recovery at any time on active treatment vs placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 10 mg
Comments 9.5 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.59 to 2.06
Estimation Comments Hazard ratio = ratio of likelihood of recovery at any time on active treatment vs placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 10 mg
Comments 24 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.78
Confidence Interval (2-Sided) 95%
0.93 to 3.43
Estimation Comments Hazard ratio = ratio of likelihood of recovery at any time on active treatment vs placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 50 mg
Comments 2 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.42
Confidence Interval (2-Sided) 95%
0.81 to 2.48
Estimation Comments Hazard ratio = ratio of likelihood of recovery at any time on active treatment vs placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 50 mg
Comments 9.5 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.93
Confidence Interval (2-Sided) 95%
1.01 to 3.66
Estimation Comments Hazard ratio = ratio of likelihood of recovery at any time on active treatment vs placebo
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 50 mg
Comments 24 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.67
Confidence Interval (2-Sided) 95%
0.86 to 3.25
Estimation Comments Hazard ratio = ratio of likelihood of recovery at any time on active treatment vs placebo
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 100 mg
Comments 2 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.09
Confidence Interval (2-Sided) 95%
1.19 to 3.69
Estimation Comments Hazard ratio = ratio of likelihood of recovery at any time on active treatment vs placebo
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 100 mg
Comments 9.5 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 5.49
Confidence Interval (2-Sided) 95%
2.75 to 10.94
Estimation Comments Hazard ratio = ratio of likelihood of recovery at any time on active treatment vs placebo
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 100 mg
Comments 24 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.91
Confidence Interval (2-Sided) 95%
1.00 to 3.64
Estimation Comments Hazard ratio = ratio of likelihood of recovery at any time on active treatment vs placebo
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 200 mg
Comments 2 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 3.60
Confidence Interval (2-Sided) 95%
2.00 to 6.48
Estimation Comments Hazard ratio = ratio of likelihood of recovery at any time on active treatment vs placebo
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 200 mg
Comments 9.5 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.03
Confidence Interval (2-Sided) 95%
1.07 to 3.87
Estimation Comments Hazard ratio = ratio of likelihood of recovery at any time on active treatment vs placebo
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo, GSK2190915 200 mg
Comments 24 Hours
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 6.07
Confidence Interval (2-Sided) 95%
2.90 to 12.71
Estimation Comments Hazard ratio = ratio of likelihood of recovery at any time on active treatment vs placebo
5.Secondary Outcome
Title Number of Participants Using a Short Acting Beta-2 Agonist (Rescue Medication) During 0 to 90 Minutes Following Exercise Challenge
Hide Description 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.
Time Frame 0 to 90 minutes following exercise challenge of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Efficacy Population.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 44 45 46 45 45
Measure Type: Count of Participants
Unit of Measure: Participants
2 Hours
1
   2.3%
1
   2.2%
2
   4.3%
1
   2.2%
0
   0.0%
9.5 Hours
1
   2.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
24 Hours
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
6.Secondary Outcome
Title Assessment of Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Hide Description 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.
Time Frame Pre dose, 2 hours, 9.5 hours and 24 hours prior to exercise challenge of treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population was defined as all participants who received at least one dose of study medication.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 44 45 47 45 45
Mean (Standard Deviation)
Unit of Measure: Millimeters of mercury (mmHg)
SBP, Mean Pre Dose 118.8  (10.21) 117.2  (10.45) 117.6  (11.53) 117.4  (11.49) 118.1  (11.33)
SBP, 2 Hours, Pre Exercise 120.1  (10.50) 119.8  (11.50) 119.1  (10.48) 119.4  (10.42) 120.3  (11.32)
SBP, 9.5 Hours, Pre Exercise 119.4  (10.50) 117.0  (8.69) 120.5  (11.37) 119.7  (10.58) 118.4  (11.86)
SBP, 24 Hours, Pre Exercise 117.2  (11.62) 116.9  (10.73) 117.4  (9.93) 117.5  (11.00) 119.8  (11.50)
DBP, Mean Pre Dose 71.7  (7.37) 71.9  (7.40) 71.5  (7.59) 71.6  (6.65) 71.9  (6.62)
DBP, 2 Hours, Pre Exercise 71.1  (6.93) 72.2  (6.09) 71.3  (7.60) 71.6  (7.76) 72.2  (6.66)
DBP, 9.5 Hours, Pre Exercise 71.9  (6.05) 70.5  (7.01) 72.0  (7.65) 71.2  (7.79) 71.9  (7.71)
DBP, 24 Hours, Pre Exercise 71.1  (7.23) 72.0  (7.84) 72.2  (6.52) 71.1  (8.25) 72.9  (8.85)
7.Secondary Outcome
Title Assessment of Vital Signs: Heart Rate (HR)
Hide Description 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.
Time Frame Pre dose, 2 hours, 9.5 hours and 24 hours prior to exercise challenge of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 44 45 47 45 45
Mean (Standard Deviation)
Unit of Measure: Beats per minute
Mean Pre Dose 64.0  (9.20) 63.0  (7.62) 64.0  (7.78) 63.6  (7.48) 64.7  (8.38)
2 Hours, Pre Exercise 67.5  (8.78) 66.2  (9.08) 67.2  (8.51) 66.8  (6.95) 67.2  (8.98)
9.5 Hours, Pre Exercise 72.9  (11.35) 69.4  (8.97) 72.8  (9.16) 72.3  (8.27) 69.4  (9.46)
24 Hours, Pre Excercise 68.3  (10.90) 65.7  (8.32) 67.7  (8.75) 65.9  (8.03) 65.6  (9.31)
8.Secondary Outcome
Title Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Hide Description 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.
Time Frame 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 period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 44 45 47 45 45
Measure Type: Count of Participants
Unit of Measure: Participants
Pre dose 1, Abnormal - NCS
15
  34.1%
20
  44.4%
20
  42.6%
18
  40.0%
19
  42.2%
Pre dose 2, Abnormal - NCS
17
  38.6%
19
  42.2%
21
  44.7%
18
  40.0%
21
  46.7%
Pre dose 3, Abnormal - NCS
23
  52.3%
21
  46.7%
20
  42.6%
19
  42.2%
22
  48.9%
2 Hours, Pre Exercise, Abnormal – NCS
21
  47.7%
22
  48.9%
15
  31.9%
19
  42.2%
20
  44.4%
2 Hours, 60 minutes, Abnormal – NCS
15
  34.1%
21
  46.7%
17
  36.2%
19
  42.2%
20
  44.4%
9.5 Hours, Pre exercise, Abnormal – NCS
12
  27.3%
18
  40.0%
17
  36.2%
16
  35.6%
18
  40.0%
24 Hours, Pre exercise, Abnormal – NCS
16
  36.4%
22
  48.9%
19
  40.4%
18
  40.0%
20
  44.4%
9.Secondary Outcome
Title Assessment of Clinical Chemistry Parameters: Albumin, Total Protein
Hide Description 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.
Time Frame Pre dose and 25 hours and 30 minutes post dose of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 44 45 47 45 45
Mean (Standard Deviation)
Unit of Measure: Gram/liter (G/L)
Albumin, Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
44.5000  (3.30961) 44.9091  (2.60427) 44.4894  (3.24956) 44.8667  (2.54594) 44.9778  (3.20148)
Albumin, 25Hours 30minutes Number Analyzed 43 participants 45 participants 47 participants 45 participants 45 participants
45.8140  (2.23879) 45.4222  (3.08581) 45.7021  (2.43091) 45.9111  (2.16188) 45.8444  (2.53122)
Total protein, Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
71.9  (5.32) 72.5  (4.05) 71.4  (5.11) 71.6  (4.16) 71.3  (4.78)
Total protein, 25Hours 30minutes Number Analyzed 43 participants 45 participants 47 participants 45 participants 45 participants
73.2  (4.00) 72.9  (3.59) 73.5  (3.97) 72.6  (2.73) 72.8  (3.72)
10.Secondary Outcome
Title Assessment of Clinical Chemistry Parameters: Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT)
Hide Description 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.
Time Frame Pre dose and 25 hours and 30 minutes post dose of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 44 45 47 45 45
Mean (Standard Deviation)
Unit of Measure: International units per liter (IU/L)
ALP, Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
76.6  (26.15) 75.5  (24.29) 75.6  (25.64) 74.6  (23.85) 75.3  (22.69)
ALP, 25 Hours 30 minutes Number Analyzed 43 participants 45 participants 47 participants 45 participants 45 participants
75.3  (23.26) 75.7  (23.75) 76.9  (27.15) 75.2  (23.71) 75.8  (25.73)
ALT, Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
30.7  (19.09) 30.1  (17.66) 31.2  (18.97) 32.2  (26.62) 39.6  (71.33)
ALT, 25 Hours 30 minutes Number Analyzed 43 participants 45 participants 47 participants 45 participants 45 participants
31.7  (20.04) 29.6  (16.08) 32.4  (19.49) 31.4  (23.34) 38.5  (66.01)
AST, Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
24.5  (13.29) 24.0  (10.26) 25.4  (14.81) 24.6  (11.42) 27.3  (31.46)
AST, 25 Hours 30 minutes Number Analyzed 43 participants 45 participants 47 participants 45 participants 45 participants
24.0  (10.14) 23.3  (8.82) 27.3  (19.39) 23.9  (9.72) 26.9  (31.33)
GGT, Pre dose 1 Number Analyzed 43 participants 41 participants 46 participants 45 participants 45 participants
29.8  (29.45) 28.1  (21.98) 31.5  (27.08) 32.8  (39.54) 30.3  (30.77)
GGT, 2 5Hours 30 minutes Number Analyzed 42 participants 43 participants 46 participants 45 participants 45 participants
29.5  (25.87) 27.7  (20.81) 32.9  (29.08) 32.8  (38.13) 31.0  (31.83)
11.Secondary Outcome
Title Assessment of Clinical Chemistry Parameters: Direct Bilirubin, Total Bilirubin, Creatinine
Hide Description 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.
Time Frame Pre dose and 25 hours and 30 minutes post dose of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 44 45 47 45 45
Mean (Standard Deviation)
Unit of Measure: Micromoles per liter (µmol/L)
Direct Bilirubin, Pre dose 1 Number Analyzed 42 participants 44 participants 46 participants 45 participants 45 participants
2.361  (1.8484) 2.332  (1.4326) 2.230  (1.8336) 2.318  (1.6769) 2.280  (2.1874)
Direct Bilirubin, 25 Hours 30 minute Number Analyzed 42 participants 45 participants 46 participants 45 participants 45 participants
2.443  (1.8938) 2.204  (1.2952) 2.453  (2.3266) 2.584  (1.8454) 2.242  (1.9230)
Total Bilirubin, Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
10.804  (5.6386) 11.348  (5.0173) 11.060  (5.6473) 11.438  (5.8652) 11.134  (7.3966)
Total Bilirubin, 25 Hours 30 minutes Number Analyzed 43 participants 45 participants 47 participants 45 participants 45 participants
10.737  (5.3078) 10.412  (4.8479) 11.388  (6.1270) 10.982  (5.8387) 10.906  (6.4426)
Creatinine, Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
83.96594  (18.34701) 87.93791  (20.15153) 86.23702  (13.21355) 86.80880  (13.90414) 85.96409  (14.50499)
Creatinine, 25 Hours 30 minutes Number Analyzed 43 participants 45 participants 47 participants 45 participants 45 participants
85.83023  (14.40704) 86.71058  (14.11612) 87.91098  (13.81935) 87.57493  (13.41632) 87.57493  (14.84895)
12.Secondary Outcome
Title Assessment of Clinical Chemistry Parameters: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/Blood Urea Nitrogen (BUN)
Hide Description 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.
Time Frame Pre dose and 25 hours and 30 minutes post dose of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 44 45 47 45 45
Mean (Standard Deviation)
Unit of Measure: Millimole per liter (mmol/L)
Calcium, Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
2.35494  (0.112125) 2.36061  (0.107377) 2.35910  (0.112041) 2.35417  (0.109681) 2.35084  (0.108088)
Calcium, 25 Hours 30 minutes Number Analyzed 43 participants 45 participants 47 participants 45 participants 45 participants
2.37605  (0.105831) 2.38300  (0.110640) 2.39308  (0.096186) 2.38078  (0.091593) 2.37136  (0.093348)
Chloride, Pre dose 1 Number Analyzed 44 participants 43 participants 47 participants 45 participants 45 participants
105.2  (1.92) 105.1  (2.04) 105.2  (2.07) 105.0  (2.34) 105.1  (2.42)
Chloride, 25 Hours 30 minutes Number Analyzed 43 participants 45 participants 47 participants 45 participants 45 participants
104.7  (2.36) 105.4  (1.85) 105.2  (2.28) 104.8  (2.05) 105.5  (2.29)
Glucose, Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
4.80162  (0.783522) 4.73601  (0.804663) 4.97937  (0.843434) 4.88735  (0.770075) 4.95273  (0.768704)
Glucose, 25 Hours 30 minutes Number Analyzed 43 participants 45 participants 47 participants 45 participants 45 participants
4.99203  (0.859137) 4.96753  (0.892300) 4.73370  (0.824460) 5.02921  (1.004730) 5.07855  (1.164605)
Potassium, Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
4.40  (0.328) 4.40  (0.456) 4.31  (0.386) 4.29  (0.320) 4.36  (0.422)
Potassium, 25 Hours 30 minutes Number Analyzed 43 participants 45 participants 47 participants 45 participants 45 participants
4.43  (0.342) 4.51  (0.362) 4.44  (0.374) 4.44  (0.322) 4.50  (0.333)
Sodium, Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
140.6  (2.16) 140.9  (2.23) 140.1  (2.17) 139.9  (2.37) 140.2  (1.87)
Sodium, 25 Hours 30 minutes Number Analyzed 43 participants 45 participants 47 participants 45 participants 44 participants
140.0  (2.13) 140.6  (2.34) 140.3  (2.18) 139.6  (2.03) 140.2  (2.14)
Urea/BUN, Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
5.8175  (1.32593) 5.6390  (1.56766) 5.7652  (1.24779) 5.7120  (1.25759) 5.6565  (1.31601)
Urea/BUN, 25 Hours 30 minutes Number Analyzed 43 participants 45 participants 47 participants 45 participants 45 participants
5.6539  (1.12605) 5.5930  (1.11343) 5.7424  (1.06537) 5.8786  (1.09666) 5.5771  (1.30126)
13.Secondary Outcome
Title Assessment of Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (TN) (ANC - Absolute Neutrophil Count), Platelet Count, White Blood Cell Count (WBC)
Hide Description 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.
Time Frame Pre dose and 25 hours and 30 minutes post dose of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 44 45 47 45 45
Mean (Standard Deviation)
Unit of Measure: Cells x 10^9 per liter
Basophils, Pre dose 1 Number Analyzed 18 participants 18 participants 17 participants 18 participants 18 participants
0.0306  (0.01326) 0.0281  (0.01065) 0.0276  (0.01133) 0.0316  (0.02112) 0.0298  (0.01261)
Basophils, 25 Hours 30 minutes Number Analyzed 17 participants 18 participants 19 participants 18 participants 18 participants
0.0242  (0.01064) 0.0303  (0.00968) 0.0333  (0.01805) 0.0282  (0.00944) 0.0252  (0.01171)
Eosinophils, Pre dose 1 Number Analyzed 18 participants 18 participants 17 participants 18 participants 18 participants
0.2638  (0.21459) 0.2574  (0.20600) 0.2392  (0.15458) 0.2563  (0.21963) 0.2166  (0.11200)
Eosinophils, 25 Hours 30 minutes Number Analyzed 17 participants 18 participants 19 participants 18 participants 18 participants
0.2241  (0.15104) 0.2610  (0.18803) 0.2431  (0.15657) 0.2271  (0.18567) 0.1974  (0.10502)
Lymphocyte, Pre dose 1 Number Analyzed 28 participants 28 participants 27 participants 28 participants 28 participants
2.2320  (0.62143) 2.2139  (0.56983) 2.3156  (0.56904) 2.3581  (0.66985) 2.1852  (0.69204)
Lymphocyte, 25 Hours 30 minutes Number Analyzed 27 participants 28 participants 29 participants 28 participants 28 participants
1.8281  (0.47068) 1.8847  (0.55807) 1.9052  (0.48399) 1.8809  (0.49456) 1.8677  (0.62646)
Monocyte, Pre dose 1 Number Analyzed 18 participants 18 participants 17 participants 18 participants 18 participants
0.4673  (0.18438) 0.4366  (0.11641) 0.4799  (0.10725) 0.4671  (0.11368) 0.4307  (0.12690)
Monocyte, 25 Hours 30 minutes Number Analyzed 17 participants 18 participants 19 participants 18 participants 18 participants
0.3912  (0.09575) 0.4289  (0.12575) 0.4489  (0.13018) 0.4190  (0.11797) 0.4084  (0.15112)
TN, Pre dose 1 Number Analyzed 28 participants 28 participants 27 participants 28 participants 28 participants
3.4340  (0.98614) 3.3645  (0.92934) 3.4151  (0.96375) 3.6047  (1.19442) 3.5448  (1.05765)
TN, 25 Hours 30 minutes Number Analyzed 27 participants 28 participants 29 participants 28 participants 28 participants
3.6062  (1.16759) 3.6962  (0.92202) 3.7720  (1.08800) 3.7813  (1.26257) 3.5289  (1.13473)
Plateletcount, Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
241.8  (58.19) 238.0  (51.85) 243.0  (47.46) 240.1  (50.26) 238.4  (49.15)
Plateletcount, 25 Hours 30 minutes Number Analyzed 43 participants 45 participants 46 participants 45 participants 45 participants
242.7  (55.97) 239.0  (48.39) 243.3  (46.73) 240.5  (50.51) 238.0  (52.59)
WBC count, Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
6.69  (1.689) 6.58  (1.638) 6.77  (1.627) 6.79  (1.726) 6.50  (1.465)
WBC count, 25 Hours 30 minutes Number Analyzed 43 participants 45 participants 46 participants 45 participants 45 participants
6.56  (1.708) 6.56  (1.434) 6.67  (1.605) 6.75  (1.650) 6.39  (1.681)
14.Secondary Outcome
Title Assessment of Hematology Parameters: Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC)
Hide Description 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.
Time Frame Pre dose and 25 hours and 30 minutes post dose of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 44 45 47 45 45
Mean (Standard Deviation)
Unit of Measure: G/L
Hemoglobin, Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
152.0  (13.75) 152.9  (13.00) 151.3  (14.44) 152.4  (12.95) 151.3  (14.58)
Hemoglobin, 25 hours 30 minutes Number Analyzed 43 participants 45 participants 46 participants 45 participants 45 participants
151.1  (12.84) 151.9  (13.80) 157.8  (45.11) 151.3  (12.93) 151.2  (13.41)
MCHC, Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
340.5  (8.55) 339.3  (8.77) 341.2  (8.35) 340.0  (8.88) 338.6  (9.40)
MCHC, 25 hours 30 minutes Number Analyzed 43 participants 45 participants 46 participants 45 participants 45 participants
340.2  (9.14) 341.1  (7.43) 340.4  (9.30) 340.4  (9.05) 339.8  (9.96)
15.Secondary Outcome
Title Assessment of Hematology Parameters: Hematocrit
Hide Description 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.
Time Frame Pre dose and 25 hours and 30 minutes post dose of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 44 45 47 45 45
Mean (Standard Deviation)
Unit of Measure: Ratio
Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
0.4463  (0.03720) 0.4503  (0.03423) 0.4431  (0.03885) 0.4480  (0.03265) 0.4465  (0.03864)
25 Hours 30 Minutes Number Analyzed 43 participants 45 participants 46 participants 45 participants 45 participants
0.4440  (0.03186) 0.4451  (0.03765) 0.4453  (0.03375) 0.4442  (0.03244) 0.4448  (0.03628)
16.Secondary Outcome
Title Assessment of Hematology Parameters: Mean Corpuscle Hemoglobin (MCH)
Hide Description 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.
Time Frame Pre dose and 25 hours and 30 minutes post dose of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only those participants with data available at the indicated time points were analyzed
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 44 45 47 45 45
Mean (Standard Deviation)
Unit of Measure: Picograms
Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
30.27  (2.078) 30.14  (2.122) 30.30  (2.032) 30.25  (2.024) 30.14  (2.008)
25 Hours 30 Minutes Number Analyzed 43 participants 45 participants 46 participants 45 participants 45 participants
30.19  (2.157) 30.20  (2.050) 30.27  (2.076) 30.18  (2.050) 30.32  (2.102)
17.Secondary Outcome
Title Assessment of Hematology Parameters: Mean Corpuscle Volume (MCV)
Hide Description 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.
Time Frame Pre dose and 25 hours and 30 minutes post dose of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 44 45 47 45 45
Mean (Standard Deviation)
Unit of Measure: Femtoliter
Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
88.85  (5.589) 88.75  (5.500) 88.80  (5.464) 88.96  (5.673) 89.06  (5.703)
25 Hours 30 Minutes Number Analyzed 43 participants 45 participants 46 participants 45 participants 45 participants
88.74  (6.116) 88.57  (5.612) 88.89  (5.696) 88.69  (5.625) 89.23  (5.730)
18.Secondary Outcome
Title Assessment of Hematology Parameters: Red Blood Cell Count (RBC)
Hide Description 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.
Time Frame Pre dose and 25 hours and 30 minutes post dose of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population. Only those participants with data available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 44 45 47 45 45
Mean (Standard Deviation)
Unit of Measure: Cells x 10^12 per liter
Pre dose 1 Number Analyzed 44 participants 44 participants 47 participants 45 participants 45 participants
5.038  (0.4699) 5.086  (0.4255) 5.005  (0.4853) 5.050  (0.4044) 5.030  (0.4756)
25 Hours 30 Minutes Number Analyzed 43 participants 45 participants 46 participants 45 participants 45 participants
5.018  (0.3819) 5.039  (0.4533) 5.023  (0.4253) 5.025  (0.4112) 4.998  (0.4557)
19.Secondary Outcome
Title Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Hide Description 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.
Time Frame Up to follow up (7 to 21 days) following last dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All Subjects Population.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 44 45 47 45 45
Measure Type: Count of Participants
Unit of Measure: Participants
Any AEs
4
   9.1%
4
   8.9%
4
   8.5%
0
   0.0%
4
   8.9%
Any SAEs
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
20.Secondary Outcome
Title Percentage Change From Baseline in Blood Leukotriene B4 (LTB4)
Hide Description 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.
Time Frame Baseline (pre dose) up to 24 Hours post dose of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 8 9 10 9 9
Median (Full Range)
Unit of Measure: Percent change
2 Hours, Pre exercise Number Analyzed 8 participants 8 participants 10 participants 9 participants 9 participants
-37.32
(-57.8 to 241.4)
-29.32
(-78.4 to 125.3)
-87.65
(-99.6 to 78.9)
-97.98
(-99.7 to 25.9)
-98.43
(-100.0 to -55.9)
9.5 Hours, Pre exercise Number Analyzed 8 participants 9 participants 10 participants 9 participants 9 participants
-14.82
(-74.6 to 239.4)
-23.43
(-93.4 to 31.1)
-87.74
(-98.4 to -23.0)
-96.53
(-99.4 to -45.2)
-99.78
(-100.0 to -95.0)
24 Hours, Pre exercise Number Analyzed 8 participants 9 participants 10 participants 9 participants 9 participants
12.59
(-57.2 to 235.1)
-9.56
(-83.3 to 167.9)
-84.49
(-96.7 to -36.3)
-70.00
(-97.8 to 209.4)
-98.75
(-99.8 to -64.9)
21.Secondary Outcome
Title Percentage Change From Baseline in Urine Leukotriene E4 (LTE4)
Hide Description 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.
Time Frame Baseline (pre dose) up to 24 Hours post dose of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PD Population. Only those participants available at the indicated time points were analyzed.
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of each treatment period.
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.
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.
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.
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.
Overall Number of Participants Analyzed 8 9 10 9 9
Median (Full Range)
Unit of Measure: Percent change
2 Hours, Pre exercise Number Analyzed 8 participants 9 participants 10 participants 9 participants 9 participants
-0.30
(-13.3 to 89.6)
-19.68
(-58.1 to 5.4)
-12.58
(-76.8 to 971.1)
-9.71
(-53.8 to 24.4)
-12.29
(-65.3 to 55.3)
2 Hours, 1 Hour 30 Minutes post dose Number Analyzed 8 participants 9 participants 10 participants 9 participants 9 participants
6.61
(-49.0 to 83.6)
-28.97
(-84.4 to 1.4)
-39.12
(-81.9 to 920.7)
-28.67
(-71.0 to 18.3)
-30.02
(-85.6 to 53.8)
9.5 Hours, Pre exercise post dose Number Analyzed 8 participants 9 participants 10 participants 9 participants 9 participants
0.82
(-42.4 to 37.9)
-52.76
(-86.0 to 0.3)
-66.74
(-86.4 to 629.8)
-59.85
(-98.2 to -23.1)
-70.43
(-87.7 to -27.3)
9.5 Hours, 1 Hour 30 Minutes post dose Number Analyzed 8 participants 9 participants 10 participants 9 participants 9 participants
0.96
(-49.0 to 88.5)
-45.05
(-89.3 to -15.9)
-61.86
(-86.6 to -0.3)
-63.67
(-83.5 to -42.1)
-81.03
(-94.4 to 5.8)
24 Hours, Pre exercise post dose Number Analyzed 8 participants 9 participants 9 participants 9 participants 9 participants
-14.04
(-50.3 to 24.1)
-29.26
(-82.6 to 21.3)
-70.37
(-88.7 to 24.9)
-72.55
(-99.5 to -5.7)
-77.07
(-99.1 to -34.2)
22.Secondary Outcome
Title Derived Pharmacokinetic (PK) Parameters for GSK2190915
Hide Description PK samples were supposed to be collected at 10 minutes prior to the exercise challenge at 2 hours, 9.5 hours and 24 hours.
Time Frame Pre dose, 2 hours, 3.5 hours, 9.5 hours, 11 hours and 24 hours following exercise challenge of each treatment period
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description:
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.
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.
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.
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.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame AEs were collected up to follow up (up to 7 to 21 days following last dose).
Adverse Event Reporting Description All Subjects Population was used.
 
Arm/Group Title Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Hide Arm/Group Description Eligible participants received Placebo matching GSK2190915 oral solution which was administered with 100 mL of water on Day 1 of the treatment period. 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. 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. 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. 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.
All-Cause Mortality
Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/44 (0.00%)   0/45 (0.00%)   0/47 (0.00%)   0/45 (0.00%)   0/45 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/44 (0.00%)   0/45 (0.00%)   0/47 (0.00%)   0/45 (0.00%)   0/45 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo GSK2190915 10 mg GSK2190915 50 mg GSK2190915 100 mg GSK2190915 200 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/44 (9.09%)   4/45 (8.89%)   4/47 (8.51%)   0/45 (0.00%)   4/45 (8.89%) 
Gastrointestinal disorders           
Diarrhoea  1  1/44 (2.27%)  1/45 (2.22%)  0/47 (0.00%)  0/45 (0.00%)  0/45 (0.00%) 
General disorders           
Fatigue  1  0/44 (0.00%)  1/45 (2.22%)  0/47 (0.00%)  0/45 (0.00%)  0/45 (0.00%) 
Injury, poisoning and procedural complications           
Contusion  1  0/44 (0.00%)  1/45 (2.22%)  0/47 (0.00%)  0/45 (0.00%)  0/45 (0.00%) 
Hand fracture  1  0/44 (0.00%)  0/45 (0.00%)  1/47 (2.13%)  0/45 (0.00%)  0/45 (0.00%) 
Investigations           
Alanine aminotransferase increased  1  0/44 (0.00%)  0/45 (0.00%)  1/47 (2.13%)  0/45 (0.00%)  0/45 (0.00%) 
Aspartate aminotransferase increased  1  0/44 (0.00%)  0/45 (0.00%)  1/47 (2.13%)  0/45 (0.00%)  0/45 (0.00%) 
Gamma-glutamyltransferase increased  1  0/44 (0.00%)  0/45 (0.00%)  1/47 (2.13%)  0/45 (0.00%)  0/45 (0.00%) 
Nervous system disorders           
Dizziness  1  2/44 (4.55%)  1/45 (2.22%)  2/47 (4.26%)  0/45 (0.00%)  0/45 (0.00%) 
Headache  1  1/44 (2.27%)  0/45 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  2/45 (4.44%) 
Tension headache  1  0/44 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  1/45 (2.22%) 
Respiratory, thoracic and mediastinal disorders           
Epistaxis  1  0/44 (0.00%)  0/45 (0.00%)  0/47 (0.00%)  0/45 (0.00%)  1/45 (2.22%) 
Skin and subcutaneous tissue disorders           
Hyperhidrosis  1  0/44 (0.00%)  1/45 (2.22%)  1/47 (2.13%)  0/45 (0.00%)  0/45 (0.00%) 
1
Term from vocabulary, MedDRA 12.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00812929     History of Changes
Other Study ID Numbers: 112025
First Submitted: December 18, 2008
First Posted: December 22, 2008
Results First Submitted: July 10, 2017
Results First Posted: September 19, 2017
Last Update Posted: September 19, 2017