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    Clinical Trial Results:
    A randomized, double-blind (sponsor unblind), placebo-controlled, multi-centered phase IIa study to evaluate the safety and efficacy of 13 weeks of once daily oral dosing of the selective androgen receptor modulator (SARM) GSK2881078 in older men and post menopausal women with COPD and muscle weakness, participating in home exercise

    Summary
    EudraCT number
    		 2017-001148-37
    Trial protocol
    		 GB  
    Global end of trial date
    19 Nov 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Jun 2020
    First version publication date
    28 Jun 2020
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    200182
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    17 Mar 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 Nov 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    1. Assess the safety and tolerability of approximately 13 weeks of dosing of GSK2881078. 2. Assess the effect of approximately 13 weeks of dosing of GSK2281078 on leg strength in older men and postmenopausal women with chronic obstructive pulmonary disease (COPD) and muscle weakness, participating in home exercise.
    Protection of trial subjects
    Not Applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    28 Feb 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Germany: 33
    Country: Number of subjects enrolled
    United Kingdom: 13
    Country: Number of subjects enrolled
    United States: 50
    Worldwide total number of subjects
    96
    EEA total number of subjects
    46
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    46
    From 65 to 84 years
    50
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This was a Phase II, double-blind, randomized, multicenter study to evaluate the safety and efficacy of GSK2881078 over 13 weeks of once daily oral dosing, first time administered in older men and post-menopausal female participants with chronic obstructive pulmonary disease (COPD) and muscle weakness, participating in home exercise.

    Pre-assignment
    Screening details
    		 A total of 200 participants were screened and 97 participants were enrolled in this study. Of which, 96 participants were randomized and received the study treatment. The remaining 1 participant was randomized without fulfilling the inclusion and exclusion criteria and therefore did not receive study medication.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo- Female Participants
    Arm description
    		 Post-menopausal female participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo was available as capsules. Post-menopausal female participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily.

    Arm title
    		 GSK2881078 1.0 mg- Female Participants
    Arm description
    		 Post-menopausal female participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 of a unit dose strength 0.5 milligram (mg) once daily over 13 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK2881078
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    GSK2881078 was available as capsules with unit dose strength of 0.5 milligram (mg). Post-menopausal female participants, 50 to 75 years of age, were administered 1.0 mg of GSK2881078 (2*0.5 mg capsules) once daily.

    Arm title
    		 Placebo- Male Participants
    Arm description
    		 Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo was available as capsules. Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily.

    Arm title
    		 GSK2881078 2.0 mg- Male Participants
    Arm description
    		 Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 of a unit dose strength 1.0 mg once daily over 13 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK2881078
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    GSK2881078 was available as capsules with unit dose strength of 1.0 mg. Male participants, 50 to 75 years of age, were administered 2.0 mg of GSK2881078 (2*1.0 mg capsules) once daily.

    Number of subjects in period 1
    		Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Started
    23
    24
    24
    25
    Completed
    21
    18
    18
    20
    Not completed
    2
    6
    6
    5
         Consent withdrawn by subject
    1
    2
    1
    -
         Physician decision
    -
    1
    -
    1
         Protocol-defined stopping criteria
    1
    -
    -
    1
         Adverse event, non-fatal
    -
    2
    5
    3
         Lost to follow-up
    -
    1
    -
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo- Female Participants
    Reporting group description
    		 Post-menopausal female participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.

    Reporting group title
    GSK2881078 1.0 mg- Female Participants
    Reporting group description
    		 Post-menopausal female participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 of a unit dose strength 0.5 milligram (mg) once daily over 13 weeks.

    Reporting group title
    Placebo- Male Participants
    Reporting group description
    		 Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.

    Reporting group title
    GSK2881078 2.0 mg- Male Participants
    Reporting group description
    		 Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 of a unit dose strength 1.0 mg once daily over 13 weeks.

    Reporting group values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants Total
    Number of subjects
    		 23 24 24 25 96
    Age categorical
    Units: Subjects
        Total Participants
    		 23 24 24 25 96
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 64.7 ( 7.16 ) 64.2 ( 7.93 ) 64.0 ( 7.27 ) 67.2 ( 6.08 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 23 24 0 0 47
        Male
    		 0 0 24 25 49
    Race/Ethnicity, Customized
    Units: Subjects
        Black or African American
    		 0 1 2 2 5
        White-White/Caucasian/European Heritage
    		 23 23 22 23 91

    End points

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    End points reporting groups
    Reporting group title
    Placebo- Female Participants
    Reporting group description
    		 Post-menopausal female participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.

    Reporting group title
    GSK2881078 1.0 mg- Female Participants
    Reporting group description
    		 Post-menopausal female participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 of a unit dose strength 0.5 milligram (mg) once daily over 13 weeks.

    Reporting group title
    Placebo- Male Participants
    Reporting group description
    		 Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.

    Reporting group title
    GSK2881078 2.0 mg- Male Participants
    Reporting group description
    		 Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 of a unit dose strength 1.0 mg once daily over 13 weeks.

    Primary: Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP)

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    End point title
    		 Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) [1]
    End point description
    SBP and DBP were measured in a seated position with a completely automated device. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Safety Population comprised of all randomized participants who received at least one dose of study medication. This population was based on the treatment the participant received. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose), Days 14, 28, 56 and 90
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    22 [2]
    23 [3]
    23 [4]
    24 [5]
    Units: Millimeters of mercury
    arithmetic mean (standard deviation)
        SBP,Day 14,n=22,23,23,24
    3.0 ( 19.63 )
    2.1 ( 11.03 )
    -2.1 ( 9.33 )
    3.1 ( 11.65 )
        SBP,Day 28,n=22,20,23,24
    3.7 ( 12.76 )
    -0.1 ( 12.82 )
    2.6 ( 14.39 )
    5.8 ( 9.49 )
        SBP,Day 56,n=21,19,20,21
    3.3 ( 14.96 )
    7.8 ( 16.38 )
    -2.4 ( 17.68 )
    1.3 ( 9.12 )
        SBP,Day 90,n=21,18,18,20
    1.0 ( 14.23 )
    7.6 ( 15.56 )
    -4.2 ( 18.52 )
    5.8 ( 18.61 )
        DBP,Day 14,n=22,23,23,24
    1.9 ( 6.88 )
    1.1 ( 6.93 )
    -3.4 ( 6.20 )
    -0.4 ( 7.47 )
        DBP,Day 28,n=22,20,23,24
    3.6 ( 7.08 )
    1.4 ( 7.58 )
    0.7 ( 7.90 )
    1.0 ( 5.36 )
        DBP,Day 56,n=21,19,20,21
    2.1 ( 7.00 )
    2.9 ( 6.07 )
    -2.5 ( 10.38 )
    -1.6 ( 8.16 )
        DBP,Day 90,n=21,18,18,20
    -1.0 ( 6.47 )
    2.9 ( 8.37 )
    -0.1 ( 12.98 )
    0.6 ( 6.95 )
    Notes
    [2] - Safety Population
    [3] - Safety Population
    [4] - Safety Population
    [5] - Safety Population
    No statistical analyses for this end point

    Primary: Change from Baseline in heart rate

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    End point title
    		 Change from Baseline in heart rate [6]
    End point description
    Heart rate was measured in a seated position with a completely automated device. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose), Days 14, 28, 56 and 90
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    22 [7]
    23 [8]
    23 [9]
    24 [10]
    Units: Beats per minute
    arithmetic mean (standard deviation)
        Day 14,n=22,23,23,24
    -0.7 ( 9.79 )
    3.3 ( 9.16 )
    1.7 ( 10.61 )
    -0.4 ( 6.60 )
        Day 28,n=22,20,23,24
    2.2 ( 8.11 )
    2.1 ( 9.64 )
    4.6 ( 10.71 )
    -1.7 ( 10.71 )
        Day 56,n=21,19,20,21
    0.2 ( 8.87 )
    -1.0 ( 8.81 )
    2.8 ( 7.17 )
    0.2 ( 6.36 )
        Day 90,n=21,18,18,20
    1.1 ( 7.99 )
    2.3 ( 10.34 )
    7.4 ( 10.23 )
    -0.6 ( 8.17 )
    Notes
    [7] - Safety Population
    [8] - Safety Population
    [9] - Safety Population
    [10] - Safety Population
    No statistical analyses for this end point

    Primary: Change from Baseline in PR Interval, QRS Duration, QT Interval, QT interval corrected for heart rate by Fridericia’s formula (QTcF) and QT interval corrected for heart rate by Bazett's formula (QTcB)

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    End point title
    		 Change from Baseline in PR Interval, QRS Duration, QT Interval, QT interval corrected for heart rate by Fridericia’s formula (QTcF) and QT interval corrected for heart rate by Bazett's formula (QTcB) [11]
    End point description
    Twelve-lead electrocardiograms (ECG) were obtained using an automated ECG machine to measure PR Interval, QRS Duration, QT Interval, QTcF Interval and QTcB Interval. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose), Days 14, 28, 56 and 90
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    22 [12]
    23 [13]
    23 [14]
    24 [15]
    Units: Milliseconds
    arithmetic mean (standard deviation)
        PR interval,Day 14,n=22,23,22,24
    -1.303 ( 9.9261 )
    -0.377 ( 7.2588 )
    -2.455 ( 12.6556 )
    -2.875 ( 24.3370 )
        PR interval,,Day 28,n=22,20,22,24
    -0.061 ( 7.9340 )
    -4.717 ( 19.3177 )
    -2.333 ( 17.5966 )
    4.139 ( 15.5796 )
        PR interval,,Day 56,n=21,19,20,21
    1.302 ( 12.1220 )
    0.596 ( 6.5250 )
    0.483 ( 7.5436 )
    10.444 ( 27.5133 )
        PR interval,,Day 90,n=21,18,17,20
    -0.270 ( 9.3111 )
    -6.167 ( 28.9117 )
    -3.373 ( 9.6845 )
    3.033 ( 20.7947 )
        QRS Duration,Day 14,n=22,23,23,24
    4.364 ( 22.8107 )
    1.362 ( 10.4736 )
    -0.464 ( 7.4791 )
    1.167 ( 4.1772 )
        QRS Duration,Day 28,n=22,20,23,24
    1.000 ( 7.7014 )
    6.200 ( 28.2707 )
    -1.478 ( 5.5047 )
    -0.542 ( 3.3547 )
        QRS Duration,Day 56,n=21,19,20,21
    -0.095 ( 5.9639 )
    1.842 ( 5.4096 )
    -1.100 ( 4.9631 )
    -0.413 ( 4.6271 )
        QRS Duration,Day 90,n=21,18,18,20
    -2.397 ( 14.1494 )
    -2.444 ( 4.5360 )
    1.333 ( 25.4163 )
    1.333 ( 6.3005 )
        QT Interval,Day 14,n=22,23,23,24
    0.576 ( 19.8239 )
    -14.290 ( 17.7216 )
    -0.638 ( 22.5431 )
    -0.597 ( 15.5697 )
        QT Interval,Day 28,n=22,20,23,24
    -1.333 ( 23.5300 )
    -16.133 ( 26.2775 )
    -4.203 ( 23.3733 )
    -1.750 ( 22.6539 )
        QT Interval,Day 56,n=21,19,20,21
    -0.127 ( 13.5567 )
    -13.947 ( 18.3657 )
    -1.533 ( 20.5897 )
    -1.857 ( 14.6881 )
        QT Interval,Day 90,n=21,18,18,20
    4.063 ( 16.9160 )
    -16.352 ( 20.7511 )
    -4.574 ( 17.1825 )
    -5.167 ( 17.7759 )
        QTcF Interval,Day 14,n=21,21,21,21
    1.749 ( 11.7762 )
    -7.143 ( 9.2710 )
    -1.235 ( 11.3507 )
    -2.698 ( 9.7085 )
        QTcF Interval,Day 28,n=21,19,21,21
    0.362 ( 15.7742 )
    -12.930 ( 11.7707 )
    -0.489 ( 10.5492 )
    -4.340 ( 12.8445 )
        QTcF Interval,Day 56,n=20,18,18,18
    1.333 ( 8.5039 )
    -12.222 ( 10.2975 )
    1.093 ( 10.0462 )
    -3.357 ( 10.5127 )
        QTcF Interval,Day 90,n=20,17,18,17
    3.600 ( 10.3526 )
    -12.627 ( 11.5776 )
    2.657 ( 12.2002 )
    -11.804 ( 11.7207 )
        QTcB Interval,Day 14,n=4,5,4,7
    -4.333 ( 26.2100 )
    2.193 ( 12.5624 )
    12.917 ( 13.6582 )
    0.571 ( 11.0180 )
        QTcB Interval,Day 28,n=4,3,4,7
    -1.167 ( 12.1549 )
    13.667 ( 24.7678 )
    -7.667 ( 8.8192 )
    -10.238 ( 11.6678 )
        QTcB Interval,Day 56,n=3,3,4,6
    -13.556 ( 11.3741 )
    -7.667 ( 9.7125 )
    13.417 ( 8.0017 )
    -9.500 ( 7.2411 )
        QTcB Interval,Day 90,n=3,3,2,6
    1.333 ( 15.9199 )
    -13.111 ( 3.0972 )
    32.000 ( 1.4142 )
    -10.278 ( 9.6088 )
    Notes
    [12] - Safety Population
    [13] - Safety Population
    [14] - Safety Population
    [15] - Safety Population
    No statistical analyses for this end point

    Primary: Number of participants with grade increase post-Baseline relative to Baseline in hematology parameters

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    End point title
    		 Number of participants with grade increase post-Baseline relative to Baseline in hematology parameters [16]
    End point description
    Blood samples were collected for the analysis of following hematology parameters: hemoglobin (Hb), lymphocyte count (Lympho), neutrophil count (Neutro) and platelet count (PC). The laboratory parameters were graded according to National Cancer Institute – Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life–threatening consequences. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Only those participants with increase to grade 3 and increase to grade 4 are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose) and up to Day 132
    Notes
    [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    23 [17]
    22 [18]
    24 [19]
    25 [20]
    Units: Participants
        Hb, Anemia, increase to Grade 3
    0
    0
    0
    0
        Hb, Anemia, increase to Grade 4
    0
    0
    0
    0
        Hb, Hb increased, increase to Grade 3
    0
    0
    0
    0
        Hb, Hb increased, increase to Grade 4
    0
    0
    0
    0
        Lympho, Lymph count decreased, increase to Grade 3
    0
    0
    0
    0
        Lympho, Lymph count decreased, increase to Grade 4
    0
    0
    0
    0
        Lympho, Lymph count increased, increase to Grade 3
    0
    0
    0
    0
        Lympho, Lymph count increased, increase to Grade 4
    0
    0
    0
    0
        Neutro,Neutro count decreased,increase to Grade 3
    0
    0
    0
    0
        Neutro,Neutro count decreased,increase to Grade 4
    0
    0
    0
    0
        PC, PC decreased,increase to Grade 3
    0
    0
    0
    0
        PC, PC decreased,increase to Grade 4
    0
    0
    0
    0
        PC, PC increased,increase to Grade 3
    0
    0
    0
    0
        PC, PC increased,increase to Grade 4
    0
    0
    0
    0
    Notes
    [17] - Safety Population
    [18] - Safety Population
    [19] - Safety Population
    [20] - Safety Population
    No statistical analyses for this end point

    Primary: Number of participants with grade increase post-Baseline relative to Baseline in clinical chemistry parameters

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    End point title
    		 Number of participants with grade increase post-Baseline relative to Baseline in clinical chemistry parameters [21]
    End point description
    Blood samples were collected for the analysis of following clinical chemistry parameters: alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), bilirubin (Bil),calcium (Ca), cholesterol (Chol), creatinine (Creat), glucose(Gl), phosphate (Phos), potassium (Pot) and sodium (Sod). The laboratory parameters were graded according to NCI-CTCAE version 4.03. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life–threatening consequences. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Values (Hyper and hypo) for Ca, Gl, Pot, Phos and Sod is presented. Only those participants with increase to grade 3 and increase to grade 4 are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose) and up to Day 132
    Notes
    [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    23 [22]
    22 [23]
    24 [24]
    25 [25]
    Units: Participants
        ALT, ALT increased, increase to Grade 3
    0
    1
    0
    1
        ALT, ALT increased, increase to Grade 4
    0
    0
    0
    0
        ALP, ALP increased, increase to Grade 3
    0
    0
    0
    0
        ALP, ALP increased, increase to Grade 4
    0
    0
    0
    0
        AST, AST increased, increase to Grade 3
    0
    0
    0
    0
        AST, AST increased, increase to Grade 4
    0
    0
    0
    0
        Bil, Blood Bil increased, increase to Grade 3
    0
    0
    0
    0
        Bil, Blood Bil increased, increase to Grade 4
    0
    0
    0
    0
        Ca, Hyper,increase to Grade 3
    0
    0
    0
    0
        Ca, Hyper,increase to Grade 4
    0
    0
    0
    0
        Ca, Hypo,increase to Grade 3
    0
    0
    0
    0
        Ca, Hypo,increase to Grade 4
    0
    0
    0
    0
        Chol, Chol high,increase to Grade 3
    0
    0
    0
    0
        Chol, Chol high,increase to Grade 4
    0
    0
    0
    0
        Creat, Creat increased,increase to Grade 3
    0
    0
    0
    0
        Creat, Creat increased,increase to Grade 4
    0
    0
    0
    0
        Gl, Hyper,increase to Grade 3
    0
    0
    0
    1
        Gl, Hyper,increase to Grade 4
    0
    0
    0
    0
        Gl, Hypo,increase to Grade 3
    0
    0
    0
    0
        Gl, Hypo,increase to Grade 4
    0
    0
    0
    0
        Phos, Hyper,increase to Grade 3
    0
    0
    0
    0
        Phos, Hyper,increase to Grade 4
    0
    0
    0
    0
        Phos, Hypo,increase to Grade 3
    0
    0
    0
    0
        Phos, Hypo,increase to Grade 4
    0
    0
    0
    0
        Pot, Hyper,increase to Grade 3
    0
    0
    0
    0
        Pot, Hyper,increase to Grade 4
    0
    0
    0
    0
        Pot, Hypo,increase to Grade 3
    0
    0
    1
    0
        Pot, Hypo,increase to Grade 4
    0
    0
    0
    0
        Sod, Hyper,increase to Grade 3
    0
    0
    0
    0
        Sod, Hyper,increase to Grade 4
    0
    0
    0
    0
        Sod, Hypo,increase to Grade 3
    2
    0
    0
    0
        Sod, Hypo,increase to Grade 4
    0
    0
    0
    0
    Notes
    [22] - Safety Population
    [23] - Safety Population
    [24] - Safety Population
    [25] - Safety Population
    No statistical analyses for this end point

    Primary: Change from Baseline in urinalysis parameter; Specific Gravity: Placebo-Female Participants

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    End point title
    		 Change from Baseline in urinalysis parameter; Specific Gravity: Placebo-Female Participants [26] [27]
    End point description
    Urine samples were collected to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine, indicated as ratio of urine density to water density. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). 99999 indicates that standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose), Days 28, 56 and 90
    Notes
    [26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo- Female Participants
    Number of subjects analysed
    21 [28]
    Units: Ratio
    arithmetic mean (standard deviation)
        Day 28,n=1
    0.0030 ( 99999 )
        Day 56,n=1
    0.0020 ( 99999 )
        Day 90,n=21
    -0.0006 ( 0.00612 )
    Notes
    [28] - Safety Population
    No statistical analyses for this end point

    Primary: Change from Baseline in urinalysis parameter; Specific Gravity: GSK2881078 1.0 mg- Female Participants

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    End point title
    		 Change from Baseline in urinalysis parameter; Specific Gravity: GSK2881078 1.0 mg- Female Participants [29] [30]
    End point description
    Urine samples were collected to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine, indicated as ratio of urine density to water density. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). 99999 indicates that standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose), Days 14 and 90
    Notes
    [29] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 GSK2881078 1.0 mg- Female Participants
    Number of subjects analysed
    18 [31]
    Units: Ratio
    arithmetic mean (standard deviation)
        Day 14,n=1
    0.000 ( 99999 )
        Day 90,n=18
    0.0049 ( 0.00711 )
    Notes
    [31] - Safety Population
    No statistical analyses for this end point

    Primary: Change from Baseline in urinalysis parameter; Specific Gravity: Male Participants

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    End point title
    		 Change from Baseline in urinalysis parameter; Specific Gravity: Male Participants [32] [33]
    End point description
    Urine samples were collected to analyze the urinalysis parameter: specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine, indicated as ratio of urine density to water density. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). 99999 indicates that standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose), Days 28 and 90
    Notes
    [32] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    [33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    19 [34]
    20 [35]
    Units: Ratio
    arithmetic mean (standard deviation)
        Day 28,n=1,1
    -0.0080 ( 99999 )
    0.0040 ( 99999 )
        Day 90,n=19,20
    0.0017 ( 0.00870 )
    0.0018 ( 0.00610 )
    Notes
    [34] - Safety Population
    [35] - Safety Population
    No statistical analyses for this end point

    Primary: Change from Baseline in urinalysis parameter; potential of hydrogen (pH): Placebo- Female Participants

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    End point title
    		 Change from Baseline in urinalysis parameter; potential of hydrogen (pH): Placebo- Female Participants [36] [37]
    End point description
    Urine samples were collected to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). 99999 indicates that standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose), Days 28, 56 and 90
    Notes
    [36] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    [37] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo- Female Participants
    Number of subjects analysed
    21 [38]
    Units: pH
    arithmetic mean (standard deviation)
        Day 28,n=1
    0.0000 ( 99999 )
        Day 56,n=1
    -0.5000 ( 99999 )
        Day 90,n=21
    0.0000 ( 0.80623 )
    Notes
    [38] - Safety Population
    No statistical analyses for this end point

    Primary: Change from Baseline in urinalysis parameter; pH: GSK2881078 1.0 mg- Female Participants

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    End point title
    		 Change from Baseline in urinalysis parameter; pH: GSK2881078 1.0 mg- Female Participants [39] [40]
    End point description
    Urine samples were collected to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). 99999 indicates that standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose), Days 14 and 90
    Notes
    [39] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    [40] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 GSK2881078 1.0 mg- Female Participants
    Number of subjects analysed
    18 [41]
    Units: pH
    arithmetic mean (standard deviation)
        Day 14,n=1
    1.0000 ( 99999 )
        Day 90,n=18
    -0.1111 ( 0.60768 )
    Notes
    [41] - Safety Population
    No statistical analyses for this end point

    Primary: Change from Baseline in urinalysis parameter; pH: Male Participants

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    End point title
    		 Change from Baseline in urinalysis parameter; pH: Male Participants [42] [43]
    End point description
    Urine samples were collected to analyze the urinalysis parameter: pH. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acidic pH (5.0 - 6.0). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). 99999 indicates that standard deviation could not be calculated as a single participant was analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose), Days 28 and 90
    Notes
    [42] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    [43] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    19 [44]
    20 [45]
    Units: pH
    arithmetic mean (standard deviation)
        Day 28,n=1,1
    1.0000 ( 99999 )
    0.5000 ( 99999 )
        Day 90,n=19,20
    -0.1579 ( 0.72749 )
    0.3000 ( 0.71451 )
    Notes
    [44] - Safety Population
    [45] - Safety Population
    No statistical analyses for this end point

    Primary: Number of participants with urinalysis dipstick results post-Baseline relative to Baseline

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    End point title
    		 Number of participants with urinalysis dipstick results post-Baseline relative to Baseline [46]
    End point description
    Urine samples were collected to analyze parameters including glucose, occult blood (OB) and protein levels by dipstick. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as increase to trace, increase to 1+ (low concentrations present), increase to 2+ (moderate concentrations present) and increase to 3+ (high concentrations present) indicating proportional concentrations in the urine sample. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data for worst-case post-Baseline relative to Baseline is presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose) and up to Day 132
    Notes
    [46] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    23 [47]
    21 [48]
    23 [49]
    24 [50]
    Units: Participants
        Glucose: increase to trace
    0
    0
    1
    0
        Glucose: increase to 1+
    0
    0
    0
    0
        Glucose: increase to 2+
    0
    0
    0
    0
        Glucose: increase to 3+
    0
    0
    0
    1
        OB: increase to trace
    1
    0
    1
    1
        OB: increase to 1+
    1
    1
    1
    0
        OB: increase to 2+
    1
    2
    0
    0
        OB: increase to 3+
    0
    0
    0
    1
        Protein: increase to trace
    2
    2
    3
    6
        Protein: increase to 1+
    0
    3
    1
    3
        Protein: increase to 2+
    0
    1
    0
    1
        Protein: increase to 3+
    0
    0
    0
    0
    Notes
    [47] - Safety Population
    [48] - Safety Population
    [49] - Safety Population
    [50] - Safety Population
    No statistical analyses for this end point

    Primary: Number of Participants with serious adverse events (SAEs) and non-serious adverse events

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    End point title
    		 Number of Participants with serious adverse events (SAEs) and non-serious adverse events [51]
    End point description
    An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function. Number of participants who had SAEs and non-SAEs are presented.
    End point type
    Primary
    End point timeframe
    Up to Day 132
    Notes
    [51] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    23 [52]
    24 [53]
    24 [54]
    25 [55]
    Units: Participants
        Non-SAEs
    15
    18
    13
    17
        SAEs
    1
    2
    2
    0
    Notes
    [52] - Safety Population
    [53] - Safety Population
    [54] - Safety Population
    [55] - Safety Population
    No statistical analyses for this end point

    Primary: Percentage change from Baseline in maximum leg press strength following 1 repetition maximum (1-RM) at Day 28

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    End point title
    		 Percentage change from Baseline in maximum leg press strength following 1 repetition maximum (1-RM) at Day 28
    End point description
    Participants continued with a one set of 5 to 10 repetitions of lifting weights using 40 to 60% of estimated maximum, after warm up. Participants, then lifted progressively heavier weights in steps, with each step separated by rest period, until participant could not complete the lift. The last successfully completed lift is 1-RM. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Percentage change from Baseline was calculated by 100*[(post-dose value minus Baseline value)/ Baseline value]. Adjusted means and standard error (SE) are presented. Analysis Population comprised of the participants in the ‘All Participants (all randomized participants who received at least one dose of study medication)’ Population having Baseline and at least one post-Baseline assessment of the treatment the participant was randomized to. Only those participants with data available at the specified data points were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 28
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [56]
    20 [57]
    22 [58]
    23 [59]
    Units: Percentage change
        arithmetic mean (standard error)
    4.82 ( 2.406 )
    9.34 ( 2.459 )
    1.55 ( 2.940 )
    9.35 ( 2.848 )
    Notes
    [56] - Analysis Population
    [57] - Analysis Population
    [58] - Analysis Population
    [59] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline leg press strength, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    4.53
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -1.3
         upper limit
    		 10.36
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline leg press strength, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    45
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    7.8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 14.76

    Primary: Percentage change from Baseline in maximum leg press strength following 1 repetition maximum (1-RM) at Day 56

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    End point title
    		 Percentage change from Baseline in maximum leg press strength following 1 repetition maximum (1-RM) at Day 56
    End point description
    Lower extremity strength was measured as 1-RM on a leg press device. Participants continued with a one set of 5 to 10 repetitions of lifting weights using 40 to 60% of estimated maximum, after warm up. Participants, then lifted progressively heavier weights in steps, with each step separated by an appropriate rest period, until participant could not complete the lift. The last successfully completed lift was recorded as the 1-RM. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Percentage change from Baseline was calculated by 100*[(post-dose value minus Baseline value)/ Baseline value]. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 56
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    20 [60]
    18 [61]
    21 [62]
    21 [63]
    Units: Percentage change
        arithmetic mean (standard error)
    0.08 ( 2.787 )
    16.78 ( 2.925 )
    5.73 ( 3.921 )
    11.07 ( 3.922 )
    Notes
    [60] - Analysis Population
    [61] - Analysis Population
    [62] - Analysis Population
    [63] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline leg press strength, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    16.71
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 9.86
         upper limit
    		 23.56
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline leg press strength, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    5.35
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -4.09
         upper limit
    		 14.78

    Primary: Percentage change from Baseline in maximum leg press strength following 1 repetition maximum (1-RM) at Day 90

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    End point title
    		 Percentage change from Baseline in maximum leg press strength following 1 repetition maximum (1-RM) at Day 90
    End point description
    Lower extremity strength was measured as 1-RM on a leg press device. Participants continued with a one set of 5 to 10 repetitions of lifting weights using 40 to 60% of estimated maximum, after warm up. Participants, then lifted progressively heavier weights in steps, with each step separated by an appropriate rest period, until participant could not complete the lift. The last successfully completed lift was recorded as the 1-RM. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Percentage change from Baseline was calculated by 100*[(post-dose value minus Baseline value)/ Baseline value]. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    19 [64]
    18 [65]
    18 [66]
    20 [67]
    Units: Percentage change
        arithmetic mean (standard error)
    12.76 ( 4.061 )
    17.93 ( 4.179 )
    7.15 ( 2.759 )
    14.17 ( 2.632 )
    Notes
    [64] - Analysis Population
    [65] - Analysis Population
    [66] - Analysis Population
    [67] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline leg press strength, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    5.17
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -4.67
         upper limit
    		 15.01
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline leg press strength, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    7.02
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.46
         upper limit
    		 13.58

    Primary: Change from Baseline in maximum leg press strength following 1 repetition maximum (1-RM) at Day 28

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    End point title
    		 Change from Baseline in maximum leg press strength following 1 repetition maximum (1-RM) at Day 28
    End point description
    Lower extremity strength was measured as 1-RM on a leg press device. Participants continued with a one set of 5 to 10 repetitions of lifting weights using 40 to 60% of estimated maximum, after warm up. Participants, then lifted progressively heavier weights in steps, with each step separated by an appropriate rest period, until participant could not complete the lift. The last successfully completed lift was recorded as the 1-RM. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 28
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [68]
    20 [69]
    22 [70]
    23 [71]
    Units: Kilograms
        arithmetic mean (standard error)
    4.2 ( 3.01 )
    10.0 ( 3.08 )
    3.0 ( 5.06 )
    16.5 ( 4.90 )
    Notes
    [68] - Analysis Population
    [69] - Analysis Population
    [70] - Analysis Population
    [71] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline leg press strength, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    5.9
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 13.2
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline leg press strength, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    45
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    13.5
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.6
         upper limit
    		 25.5

    Primary: Change from Baseline in maximum leg press strength following 1 repetition maximum (1-RM) at Day 56

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    End point title
    		 Change from Baseline in maximum leg press strength following 1 repetition maximum (1-RM) at Day 56
    End point description
    Lower extremity strength was measured as 1-RM on a leg press device. Participants continued with a one set of 5 to 10 repetitions of lifting weights using 40 to 60% of estimated maximum, after warm up. Participants, then lifted progressively heavier weights in steps, with each step separated by an appropriate rest period, until participant could not complete the lift. The last successfully completed lift was recorded as the 1-RM. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 56
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    20 [72]
    18 [73]
    21 [74]
    21 [75]
    Units: Kilograms
        arithmetic mean (standard error)
    0.6 ( 4.29 )
    21.3 ( 4.50 )
    8.3 ( 7.69 )
    15.7 ( 7.69 )
    Notes
    [72] - Analysis Population
    [73] - Analysis Population
    [74] - Analysis Population
    [75] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline leg press strength, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    20.7
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 10.1
         upper limit
    		 31.2
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline leg press strength, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    7.3
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -11.1
         upper limit
    		 25.8

    Primary: Change from Baseline in maximum leg press strength following 1 repetition maximum (1-RM) at Day 90

    		 Close Top of page
    End point title
    		 Change from Baseline in maximum leg press strength following 1 repetition maximum (1-RM) at Day 90
    End point description
    Lower extremity strength was measured as 1-RM on a leg press device. Participants continued with a one set of 5 to 10 repetitions of lifting weights using 40 to 60% of estimated maximum, after warm up. Participants, then lifted progressively heavier weights in steps, with each step separated by an appropriate rest period, until participant could not complete the lift. The last successfully completed lift was recorded as the 1-RM. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Primary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    19 [76]
    18 [77]
    18 [78]
    20 [79]
    Units: Kilograms
        arithmetic mean (standard error)
    12.3 ( 4.31 )
    20.3 ( 4.45 )
    14.2 ( 5.17 )
    26.0 ( 4.91 )
    Notes
    [76] - Analysis Population
    [77] - Analysis Population
    [78] - Analysis Population
    [79] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline leg press strength, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -2.5
         upper limit
    		 18.4
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline leg press strength, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    11.8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 24

    Secondary: Change from Baseline in appendicular lean mass as assessed by dual-energy X-ray absorptiometry (DXA) at Day 28

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    End point title
    		 Change from Baseline in appendicular lean mass as assessed by dual-energy X-ray absorptiometry (DXA) at Day 28
    End point description
    Participants were asked to lie on a padded platform while a mechanical arm passed over their body. Appendicular lean mass was calculated from the regional lean mass measurements of the arms and legs using DXA. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 28
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [80]
    19 [81]
    20 [82]
    22 [83]
    Units: Kilograms
        arithmetic mean (standard error)
    -0.240 ( 0.0974 )
    0.642 ( 0.1023 )
    0.055 ( 0.1920 )
    0.346 ( 0.1831 )
    Notes
    [80] - Analysis Population
    [81] - Analysis Population
    [82] - Analysis Population
    [83] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline appendicular lean mass, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.882
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.643
         upper limit
    		 1.121
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline appendicular lean mass, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.291
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.156
         upper limit
    		 0.738

    Secondary: Change from Baseline in appendicular lean mass as assessed by dual-energy X-ray absorptiometry (DXA) at Day 56

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    End point title
    		 Change from Baseline in appendicular lean mass as assessed by dual-energy X-ray absorptiometry (DXA) at Day 56
    End point description
    Participants were asked to lie on a padded platform while a mechanical arm passed over their body. Appendicular lean mass was calculated from the regional lean mass measurements of the arms and legs using DXA. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 56
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [84]
    17 [85]
    17 [86]
    18 [87]
    Units: Kilograms
        arithmetic mean (standard error)
    -0.134 ( 0.1410 )
    0.848 ( 0.1540 )
    -0.464 ( 0.1887 )
    0.663 ( 0.1829 )
    Notes
    [84] - Analysis Population
    [85] - Analysis Population
    [86] - Analysis Population
    [87] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline appendicular lean mass, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.982
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.629
         upper limit
    		 1.334
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline appendicular lean mass, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.127
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.682
         upper limit
    		 1.571

    Secondary: Change from Baseline in appendicular lean mass as assessed by dual-energy X-ray absorptiometry (DXA) at Day 90

    		 Close Top of page
    End point title
    		 Change from Baseline in appendicular lean mass as assessed by dual-energy X-ray absorptiometry (DXA) at Day 90
    End point description
    Participants were asked to lie on a padded platform while a mechanical arm passed over their body. Appendicular lean mass was calculated from the regional lean mass measurements of the arms and legs using DXA. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [88]
    17 [89]
    15 [90]
    18 [91]
    Units: Kilograms
        arithmetic mean (standard error)
    -0.434 ( 0.1657 )
    0.946 ( 0.1818 )
    -0.225 ( 0.2306 )
    0.899 ( 0.2117 )
    Notes
    [88] - Analysis Population
    [89] - Analysis Population
    [90] - Analysis Population
    [91] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline appendicular lean mass, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    33
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.124
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.594
         upper limit
    		 1.654
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline appendicular lean mass, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.38
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.964
         upper limit
    		 1.795

    Secondary: Change from Baseline in total lean mass as assessed by dual-energy X-ray absorptiometry (DXA) at Day 28

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    End point title
    		 Change from Baseline in total lean mass as assessed by dual-energy X-ray absorptiometry (DXA) at Day 28
    End point description
    Participants were asked to lie on a padded platform while a mechanical arm passed over their body. Total lean mass was measured using DXA. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 28
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [92]
    19 [93]
    20 [94]
    22 [95]
    Units: Kilograms
        arithmetic mean (standard error)
    -0.017 ( 0.2004 )
    1.150 ( 0.2106 )
    0.075 ( 0.3004 )
    0.998 ( 0.2869 )
    Notes
    [92] - Analysis Population
    [93] - Analysis Population
    [94] - Analysis Population
    [95] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline total lean mass, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.923
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.222
         upper limit
    		 1.623
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline total lean mass, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.167
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.677
         upper limit
    		 1.658

    Secondary: Change from Baseline in total lean mass as assessed by dual-energy X-ray absorptiometry (DXA) at Day 56

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    End point title
    		 Change from Baseline in total lean mass as assessed by dual-energy X-ray absorptiometry (DXA) at Day 56
    End point description
    Participants were asked to lie on a padded platform while a mechanical arm passed over their body. Total lean mass was measured using DXA. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 56
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [96]
    17 [97]
    17 [98]
    18 [99]
    Units: Kilograms
        arithmetic mean (standard error)
    -0.564 ( 0.2372 )
    1.522 ( 0.2587 )
    -0.373 ( 0.3820 )
    1.327 ( 0.3700 )
    Notes
    [96] - Analysis Population
    [97] - Analysis Population
    [98] - Analysis Population
    [99] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline total lean mass, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    2.085
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.493
         upper limit
    		 2.678
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline total lean mass, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    1.7
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.801
         upper limit
    		 2.6

    Secondary: Change from Baseline in total lean mass as assessed by dual-energy X-ray absorptiometry (DXA) at Day 90

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    End point title
    		 Change from Baseline in total lean mass as assessed by dual-energy X-ray absorptiometry (DXA) at Day 90
    End point description
    Participants were asked to lie on a padded platform while a mechanical arm passed over their body. Total lean mass was measured using DXA. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [100]
    17 [101]
    15 [102]
    18 [103]
    Units: Kilograms
        arithmetic mean (standard error)
    -0.531 ( 0.3349 )
    1.577 ( 0.3666 )
    -0.424 ( 0.5056 )
    1.689 ( 0.4666 )
    Notes
    [100] - Analysis Population
    [101] - Analysis Population
    [102] - Analysis Population
    [103] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline total lean mass, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    33
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    2.113
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0.949
         upper limit
    		 3.277
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline total lean mass, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    2.108
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 1.271
         upper limit
    		 2.945

    Secondary: Change from Baseline in total Short Physical Performance Battery (SPPB) score at Day 28

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    End point title
    		 Change from Baseline in total Short Physical Performance Battery (SPPB) score at Day 28
    End point description
    Participants were assessed for balance, time for chair rise and gait speed. These are the three components of SPPB. Each component was scored from 0 to 4. The total SPPB score was calculated by taking sum of scores of all 3 components, which ranged from 0 (worst performance) to 12 (best performance). Higher scores indicated better performance. Scores 10 to 12 indicated 'fit/normal' and scores <=7 indicated frail participant. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 28
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [104]
    20 [105]
    22 [106]
    23 [107]
    Units: Scores on a scale
        arithmetic mean (standard error)
    0.3 ( 0.25 )
    0.4 ( 0.26 )
    0.2 ( 0.19 )
    0.3 ( 0.18 )
    Notes
    [104] - Analysis Population
    [105] - Analysis Population
    [106] - Analysis Population
    [107] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline SPPB total score, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    0
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 0.6
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline SPPB total score, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    45
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    0
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 0.5

    Secondary: Change from Baseline in total Short Physical Performance Battery (SPPB) score at Day 56

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    End point title
    		 Change from Baseline in total Short Physical Performance Battery (SPPB) score at Day 56
    End point description
    Participants were assessed for balance, time for chair rise and gait speed. These are the three components of SPPB. Each component was scored from 0 to 4. The total SPPB score was calculated by taking sum of scores of all 3 components, which ranged from 0 (worst performance) to 12 (best performance). Higher scores indicated better performance. Scores 10 to 12 indicated 'fit/normal' and scores <=7 indicated frail participant. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 56
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [108]
    19 [109]
    21 [110]
    21 [111]
    Units: Scores on a scale
        arithmetic mean (standard error)
    0.4 ( 0.24 )
    0.4 ( 0.25 )
    0.1 ( 0.24 )
    0.4 ( 0.24 )
    Notes
    [108] - Analysis Population
    [109] - Analysis Population
    [110] - Analysis Population
    [111] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline SPPB total score, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    0
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.6
         upper limit
    		 0.6
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline SPPB total score, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.3
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.2
         upper limit
    		 0.9

    Secondary: Change from Baseline in total Short Physical Performance Battery (SPPB) score at Day 90

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    End point title
    		 Change from Baseline in total Short Physical Performance Battery (SPPB) score at Day 90
    End point description
    Participants were assessed for balance, time for chair rise and gait speed. These are the three components of SPPB. Each component was scored from 0 to 4. The total SPPB score was calculated by taking sum of scores of all 3 components, which ranged from 0 (worst performance) to 12 (best performance). Higher scores indicated better performance. Scores 10 to 12 indicated 'fit/normal' and scores <=7 indicated frail participant. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [112]
    18 [113]
    18 [114]
    20 [115]
    Units: Scores on a scale
        arithmetic mean (standard error)
    0.3 ( 0.26 )
    0.5 ( 0.28 )
    0.4 ( 0.23 )
    0.5 ( 0.22 )
    Notes
    [112] - Analysis Population
    [113] - Analysis Population
    [114] - Analysis Population
    [115] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline SPPB total score, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.4
         upper limit
    		 0.9
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline SPPB total score, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 0.6

    Secondary: Change from Baseline in 'time for chair rise' as assessed by SPPB at Day 28

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    End point title
    		 Change from Baseline in 'time for chair rise' as assessed by SPPB at Day 28
    End point description
    'Time for chair rise' is one of the 3 components of SPPB, which was assessed by repeated chair stand test and calculated as time for five successful chair stands measured in seconds. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 28
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [116]
    20 [117]
    22 [118]
    23 [119]
    Units: Seconds
        arithmetic mean (standard error)
    -0.644 ( 0.6333 )
    -1.196 ( 0.6491 )
    -0.464 ( 0.3841 )
    -0.537 ( 0.3763 )
    Notes
    [116] - Analysis Population
    [117] - Analysis Population
    [118] - Analysis Population
    [119] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and corresponding Baseline time for chair rise, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.553
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -2.082
         upper limit
    		 0.977
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and corresponding Baseline time for chair rise, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    45
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.073
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.977
         upper limit
    		 0.832

    Secondary: Change from Baseline in 'time for chair rise' as assessed by SPPB at Day 56

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    End point title
    		 Change from Baseline in 'time for chair rise' as assessed by SPPB at Day 56
    End point description
    'Time for chair rise' is one of the 3 components of SPPB, which was assessed by repeated chair stand test and calculated as time for five successful chair stands measured in seconds. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 56
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [120]
    19 [121]
    21 [122]
    21 [123]
    Units: Seconds
        arithmetic mean (standard error)
    -1.207 ( 0.5912 )
    -2.023 ( 0.6124 )
    -0.323 ( 0.5294 )
    -0.160 ( 0.5282 )
    Notes
    [120] - Analysis Population
    [121] - Analysis Population
    [122] - Analysis Population
    [123] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and corresponding Baseline time for chair rise, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.816
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -2.252
         upper limit
    		 0.619
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and corresponding Baseline time for chair rise, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.163
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -1.096
         upper limit
    		 1.422

    Secondary: Change from Baseline in 'time for chair rise' as assessed by SPPB at Day 90

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    End point title
    		 Change from Baseline in 'time for chair rise' as assessed by SPPB at Day 90
    End point description
    ‘Time for chair rise' is one of the 3 components of SPPB, which was assessed by repeated chair stand test and calculated as time for five successful chair stands measured in seconds. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [124]
    18 [125]
    18 [126]
    20 [127]
    Units: Seconds
        arithmetic mean (standard error)
    -1.070 ( 0.6956 )
    -2.030 ( 0.7362 )
    1.144 ( 1.4013 )
    -0.793 ( 1.3401 )
    Notes
    [124] - Analysis Population
    [125] - Analysis Population
    [126] - Analysis Population
    [127] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and corresponding Baseline time for chair rise, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.96
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -2.668
         upper limit
    		 0.748
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and corresponding Baseline time for chair rise, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.937
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -5.208
         upper limit
    		 1.333

    Secondary: Change from Baseline in 'time for fastest walk for 4 meter' as assessed by SPPB at Day 28

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    End point title
    		 Change from Baseline in 'time for fastest walk for 4 meter' as assessed by SPPB at Day 28
    End point description
    ''Time for fastest walk for 4 meter' was assessed by SPPB using 4 meter gait speed test. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 28
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [128]
    20 [129]
    22 [130]
    23 [131]
    Units: Seconds
        arithmetic mean (standard error)
    -0.236 ( 0.1132 )
    -0.277 ( 0.1161 )
    -0.167 ( 0.1133 )
    -0.110 ( 0.1108 )
    Notes
    [128] - Analysis Population
    [129] - Analysis Population
    [130] - Analysis Population
    [131] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and corresponding Baseline Time for fastest walk for 4 meter, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.04
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.314
         upper limit
    		 0.233
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and corresponding Baseline Time for fastest walk for 4 meter, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    45
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    0.058
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.209
         upper limit
    		 0.324

    Secondary: Change from Baseline in 'time for fastest walk for 4 meter' as assessed by SPPB at Day 56

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    End point title
    		 Change from Baseline in 'time for fastest walk for 4 meter' as assessed by SPPB at Day 56
    End point description
    ‘Time for fastest walk for 4 meter' was assessed by SPPB using 4 meter gait speed test. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 56
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [132]
    19 [133]
    21 [134]
    21 [135]
    Units: Seconds
        arithmetic mean (standard error)
    0.010 ( 0.1487 )
    -0.276 ( 0.1560 )
    -0.093 ( 0.1437 )
    -0.284 ( 0.1438 )
    Notes
    [132] - Analysis Population
    [133] - Analysis Population
    [134] - Analysis Population
    [135] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and corresponding Baseline Time for fastest walk for 4 meter, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.287
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.65
         upper limit
    		 0.077
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and corresponding Baseline Time for fastest walk for 4 meter, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.191
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.534
         upper limit
    		 0.152

    Secondary: Change from Baseline in 'time for fastest walk for 4 meter' as assessed by SPPB at Day 90

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    End point title
    		 Change from Baseline in 'time for fastest walk for 4 meter' as assessed by SPPB at Day 90
    End point description
    ‘Time for fastest walk for 4 meter' was assessed by SPPB using 4 meter gait speed test. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Analysis was performed using mixed model repeated measures. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [136]
    18 [137]
    18 [138]
    20 [139]
    Units: Seconds
        arithmetic mean (standard error)
    -0.043 ( 0.2194 )
    -0.055 ( 0.2361 )
    -0.130 ( 0.1331 )
    -0.360 ( 0.1275 )
    Notes
    [136] - Analysis Population
    [137] - Analysis Population
    [138] - Analysis Population
    [139] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and corresponding Baseline Time for fastest walk for 4 meter, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.231
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.541
         upper limit
    		 0.08
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and corresponding Baseline Time for fastest walk for 4 meter, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.012
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.555
         upper limit
    		 0.532

    Secondary: Change from Baseline in constant work rate (CWR) duration from endurance shuttle walking test

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    End point title
    		 Change from Baseline in constant work rate (CWR) duration from endurance shuttle walking test
    End point description
    The endurance shuttle walk test is a CWR test requiring the participant to walk around a flat 10 meter track at a constant individualized pace. The test was externally paced, set to elicit a maximal exercise response (pace was based on a fixed percentage of prior incremental shuttle walk test performance, which determined a participant’s peak exercise capacity). CWR duration is the time in seconds required by a participant to cover a flat 10 meter track during this test. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using analysis of covariance (ANCOVA) model. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    19 [140]
    16 [141]
    18 [142]
    20 [143]
    Units: Seconds
        least squares mean (standard error)
    -6.5 ( 26.78 )
    4.6 ( 29.25 )
    105.1 ( 54.94 )
    -44.2 ( 51.97 )
    Notes
    [140] - Analysis Population
    [141] - Analysis Population
    [142] - Analysis Population
    [143] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by ANCOVA model with Baseline CWR duration as the covariate adjusting for the treatment.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Least Square Means
    Point estimate
    -149.3
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -280.6
         upper limit
    		 -18.1
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by ANCOVA model with Baseline CWR duration as the covariate adjusting for the treatment.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Least Square Means
    Point estimate
    11.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -57.1
         upper limit
    		 79.2

    Secondary: Change from Baseline in peak performance from incremental shuttle walking test

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    End point title
    		 Change from Baseline in peak performance from incremental shuttle walking test
    End point description
    An incremental shuttle walk test is an externally paced maximal exercise test which determined a participant’s peak exercise capacity. The maximum duration of the test is 20 minutes. Peak performance was measured in meters, which was defined as the maximum distance covered by a participant until the participant can no longer continue walking during this test. Baseline was defined as the highest non-missing pre-dose assessment from Day -9 and Day 1. Analysis was performed using ANCOVA model. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Highest non-missing pre-dose assessment from Day-9 and Day 1), Day 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    19 [144]
    18 [145]
    18 [146]
    20 [147]
    Units: Meters
        least squares mean (standard error)
    -10.5 ( 14.76 )
    -17.2 ( 15.16 )
    -7.5 ( 15.84 )
    -42.3 ( 15.02 )
    Notes
    [144] - Analysis Population
    [145] - Analysis Population
    [146] - Analysis Population
    [147] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by ANCOVA model with Baseline peak performance as the covariate adjusting for the treatment.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Least Square Means
    Point estimate
    -6.7
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -42.7
         upper limit
    		 29.2
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by ANCOVA model with Baseline peak performance as the covariate adjusting for the treatment.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Least Square Means
    Point estimate
    -34.8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -72
         upper limit
    		 2.4

    Secondary: Change from Baseline in chronic obstructive pulmonary disease (COPD) assessment test (CAT) score at Day 56

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    End point title
    		 Change from Baseline in chronic obstructive pulmonary disease (COPD) assessment test (CAT) score at Day 56
    End point description
    The CAT is a short and simple participant-completed questionnaire which was developed for use in routine clinical practice to measure the health status of participants with COPD. The CAT is an 8-item questionnaire suitable for completion by all participants diagnosed with COPD. Participants rated their experience on a 6-point scale, ranging from 0 (no impairment) to 5 (maximum impairment). A total CAT score was calculated by summing the non-missing scores of the eight items with a scoring range of 0-40. Higher scores indicated more severe disease impact. Day 1 (Pre-dose) was considered as a Baseline. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 56
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [148]
    19 [149]
    21 [150]
    21 [151]
    Units: Scores on a Scale
        arithmetic mean (standard error)
    -0.8 ( 0.92 )
    -1.2 ( 0.97 )
    -0.4 ( 1.14 )
    -1.0 ( 1.14 )
    Notes
    [148] - Analysis Population
    [149] - Analysis Population
    [150] - Analysis Population
    [151] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline CAT score, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    40
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -2.6
         upper limit
    		 1.9
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline CAT score, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    42
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.7
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -3.4
         upper limit
    		 2.1

    Secondary: Change from Baseline in chronic obstructive pulmonary disease (COPD) assessment test (CAT) score at Day 90

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    End point title
    		 Change from Baseline in chronic obstructive pulmonary disease (COPD) assessment test (CAT) score at Day 90
    End point description
    The CAT is a short and simple participant-completed questionnaire which was developed for use in routine clinical practice to measure the health status of participants with COPD. The CAT is an 8-item questionnaire suitable for completion by all participants diagnosed with COPD. Participants rated their experience on a 6-point scale, ranging from 0 (no impairment) to 5 (maximum impairment). A total CAT score was calculated by summing the non-missing scores of the eight items with a scoring range of 0-40. Higher scores indicated more severe disease impact. Day 1 (Pre-dose) was considered as a Baseline. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [152]
    18 [153]
    18 [154]
    20 [155]
    Units: Scores on a Scale
        arithmetic mean (standard error)
    -1.3 ( 0.79 )
    -2.2 ( 0.85 )
    -1.4 ( 0.94 )
    0.8 ( 0.90 )
    Notes
    [152] - Analysis Population.
    [153] - Analysis Population.
    [154] - Analysis Population.
    [155] - Analysis Population.
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline CAT score, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    2.2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 4.5
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and Baseline CAT score, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.9
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -2.9
         upper limit
    		 1.1

    Secondary: Change from Baseline in participant reported outcome (PRO)active individual component: Difficulty score at Day 56

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    End point title
    		 Change from Baseline in participant reported outcome (PRO)active individual component: Difficulty score at Day 56
    End point description
    The daily PROactive instrument consisted of a PRO questionnaire and an activity monitor to measure participant experience of physical activity. It consisted of 9-item daily assessments covering 2 different domains (amount and difficulty). The ‘amount’ domain was covered by 2 questions combined with 2 activity monitor outputs. The ‘difficulty’ domain was covered by 5 questions. Individual domains were scored by simple adding items, gave raw score values 0 to 17 for ‘amount’ and 0 to 20 for ‘difficulty’. The raw scores were then transformed to a 0 to 100 Rasch analysis based scale for each domain. Higher scores indicated worse experience with physical activity. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day -9) and Day 56
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    17 [156]
    12 [157]
    12 [158]
    13 [159]
    Units: Scores on a Scale
        arithmetic mean (standard error)
    3.7 ( 1.59 )
    -1.1 ( 1.80 )
    1.3 ( 2.16 )
    -0.8 ( 2.08 )
    Notes
    [156] - Analysis Population
    [157] - Analysis Population
    [158] - Analysis Population
    [159] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and corresponding Baseline difficulty scores, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    29
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -4.7
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -8.9
         upper limit
    		 -0.6
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and corresponding Baseline difficulty scores, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -2.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -7.2
         upper limit
    		 3.1

    Secondary: Change from Baseline in participant reported outcome (PRO)active individual component: Difficulty score at Day 90

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    End point title
    		 Change from Baseline in participant reported outcome (PRO)active individual component: Difficulty score at Day 90
    End point description
    The daily PROactive instrument consisted of a PRO questionnaire and an activity monitor to measure participant experience of physical activity. It consisted of 9-item daily assessments covering 2 different domains (amount and difficulty). The ‘amount’ domain was covered by 2 questions combined with 2 activity monitor outputs. The ‘difficulty’ domain was covered by 5 questions. Individual domains were scored by simple adding items, gave raw score values 0 to 17 for ‘amount’ and 0 to 20 for ‘difficulty’. The raw scores were then transformed to a 0 to 100 Rasch analysis based scale for each domain. Higher scores indicated worse experience with physical activity. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day -9) and Day 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    15 [160]
    17 [161]
    13 [162]
    11 [163]
    Units: Scores on a Scale
        arithmetic mean (standard error)
    2.0 ( 1.90 )
    -2.9 ( 1.84 )
    2.8 ( 2.56 )
    -1.2 ( 2.65 )
    Notes
    [160] - Analysis Population
    [161] - Analysis Population
    [162] - Analysis Population
    [163] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and corresponding Baseline difficulty scores, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -4.9
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -9.5
         upper limit
    		 -0.4
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and corresponding Baseline difficulty scores, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -4.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -10.3
         upper limit
    		 2.2

    Secondary: Change from Baseline in participant reported outcome (PRO)active individual component: Amount score at Day 56

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    End point title
    		 Change from Baseline in participant reported outcome (PRO)active individual component: Amount score at Day 56
    End point description
    The daily PROactive instrument consisted of a PRO questionnaire and an activity monitor to measure participant experience of physical activity. It consisted of 9-item daily assessments covering 2 different domains (amount and difficulty). The ‘amount’ domain was covered by 2 questions combined with 2 activity monitor outputs. The ‘difficulty’ domain was covered by 5 questions. Individual domains were scored by simple adding items, gave raw score values 0 to 17 for ‘amount’ and 0 to 20 for ‘difficulty’. The raw scores were then transformed to a 0 to 100 Rasch analysis based scale for each domain. Higher scores indicated worse experience with physical activity. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day -9) and Day 56
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    17 [164]
    12 [165]
    12 [166]
    13 [167]
    Units: Scores on a Scale
        arithmetic mean (standard error)
    3.3 ( 1.09 )
    0.2 ( 1.24 )
    2.5 ( 1.83 )
    2.3 ( 1.77 )
    Notes
    [164] - Analysis Population
    [165] - Analysis Population
    [166] - Analysis Population
    [167] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and corresponding Baseline amount scores, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    29
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -3.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -5.9
         upper limit
    		 -0.3
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates: treatment, Day, treatment* Day and corresponding Baseline amount scores, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -4.6
         upper limit
    		 4.2

    Secondary: Change from Baseline in participant reported outcome (PRO)active individual component: Amount score at Day 90

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    End point title
    		 Change from Baseline in participant reported outcome (PRO)active individual component: Amount score at Day 90
    End point description
    The daily PROactive instrument consisted of a PRO questionnaire and an activity monitor to measure participant experience of physical activity. It consisted of 9-item daily assessments covering 2 different domains (amount and difficulty). The ‘amount’ domain was covered by 2 questions combined with 2 activity monitor outputs. The ‘difficulty’ domain was covered by 5 questions. Individual domains were scored by simple adding items, gave raw score values 0 to 17 for ‘amount’ and 0 to 20 for ‘difficulty’. The raw scores were then transformed to a 0 to 100 Rasch analysis based scale for each domain. Higher scores indicated worse experience with physical activity. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Adjusted means and SE are presented. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day -9) and Day 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    15 [168]
    17 [169]
    13 [170]
    11 [171]
    Units: Scores on a Scale
        arithmetic mean (standard error)
    -0.2 ( 2.05 )
    3.8 ( 1.98 )
    -0.8 ( 2.33 )
    2.7 ( 2.47 )
    Notes
    [168] - Analysis Population
    [169] - Analysis Population
    [170] - Analysis Population
    [171] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by repeated measures mixed model including the covariates; treatment, Day, treatment* Day and corresponding Baseline amount scores, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    3.5
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -2.3
         upper limit
    		 9.4
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by repeated measures mixed model including the covariates; treatment, Day, treatment* Day and corresponding Baseline amount scores, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 8.8

    Secondary: Change from Baseline in participant reported outcome (PRO)active total score at Day 56

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    End point title
    		 Change from Baseline in participant reported outcome (PRO)active total score at Day 56
    End point description
    The daily PROactive instrument consisted of a PRO questionnaire and an activity monitor to measure physical activity. It consisted of 9-item daily assessments covering 2 different domains(amount and difficulty). The‘amount’domain was covered by 2 questions combined with 2 activity monitor outputs. The ‘difficulty’domain was covered by 5 questions. Individual domains were scored by simple adding items, gave raw score values 0 to 17 for‘amount’and 0 to 20 for‘difficulty. The raw scores were then transformed to a 0 to 100 Rasch scale. The ‘total score’ was obtained by calculating the average between two domains (ranged from 0 to 100). Higher scores indicated worse experience with physical activity. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day -9) and Day 56
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    17 [172]
    12 [173]
    12 [174]
    13 [175]
    Units: Scores on a Scale
        arithmetic mean (standard error)
    3.7 ( 0.89 )
    -0.5 ( 1.03 )
    2.1 ( 1.09 )
    0.5 ( 1.05 )
    Notes
    [172] - Analysis Population
    [173] - Analysis Population
    [174] - Analysis Population
    [175] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates; treatment, Day, treatment* Day and corresponding Baseline total scores, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    25
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1.5
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -4.1
         upper limit
    		 1.1
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates; treatment, Day, treatment* Day and corresponding Baseline total scores, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    29
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -4.2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -6.5
         upper limit
    		 -1.9

    Secondary: Change from Baseline in participant reported outcome (PRO)active total score at Day 90

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    End point title
    		 Change from Baseline in participant reported outcome (PRO)active total score at Day 90
    End point description
    The daily PROactive instrument consisted of a PRO questionnaire and an activity monitor to measure physical activity. It consisted of 9-item daily assessments covering 2 different domains(amount and difficulty). The‘amount’domain was covered by 2 questions combined with 2 activity monitor outputs. The ‘difficulty’domain was covered by 5 questions. Individual domains were scored by simple adding items, gave raw score values 0 to 17 for‘amount’and 0 to 20 for‘difficulty. The raw scores were then transformed to a 0 to 100 Rasch scale. The ‘total score’ was obtained by calculating the average between two domains (ranged from 0 to 100). Higher scores indicated worse experience with physical activity. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day -9) and Day 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    15 [176]
    17 [177]
    13 [178]
    11 [179]
    Units: Scores on a Scale
        arithmetic mean (standard error)
    1.3 ( 1.20 )
    0.3 ( 1.14 )
    1.2 ( 1.57 )
    0.5 ( 1.66 )
    Notes
    [176] - Analysis Population
    [177] - Analysis Population
    [178] - Analysis Population
    [179] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates; treatment, Day, treatment* Day and corresponding Baseline total scores, with Day as the repeated factor.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    24
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -0.7
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -4.6
         upper limit
    		 3.2
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by mixed model repeated measures including the covariates; treatment, Day, treatment* Day and corresponding Baseline total scores, with Day as the repeated factor.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    32
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Mean difference (net)
    Point estimate
    -1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -3.8
         upper limit
    		 1.8

    Secondary: Change from Baseline in steps per day (physical activity measure) as assessed via an accelerometer

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    End point title
    		 Change from Baseline in steps per day (physical activity measure) as assessed via an accelerometer
    End point description
    Steps per day was assessed using an accelerometer, a clinically validated physical activity monitor which was used to measure the levels of physical activity. Participants wore an accelerometer for 7 days during individual timepoint. Values at Baseline, Day 56 and Day 90 were the average values collected from an accelerometer for 7 days after the Day -9, Day 56 and Day 90. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day -9), Days 56 and 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    17 [180]
    17 [181]
    14 [182]
    17 [183]
    Units: Steps per day
    arithmetic mean (standard deviation)
        Day 56,n=17,14,14,17
    285.19 ( 1289.604 )
    389.58 ( 1322.701 )
    120.41 ( 1282.092 )
    -17.40 ( 1334.539 )
        Day 90,n=17,17,14,14
    -246.45 ( 756.414 )
    786.21 ( 1439.988 )
    -527.07 ( 1077.747 )
    611.36 ( 1499.559 )
    Notes
    [180] - Analysis Population
    [181] - Analysis Population
    [182] - Analysis Population
    [183] - Analysis Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in vector magnitude unit per wear time (physical activity measure) as assessed via an accelerometer

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    End point title
    		 Change from Baseline in vector magnitude unit per wear time (physical activity measure) as assessed via an accelerometer
    End point description
    Vector magnitude unit per wear time was assessed using an accelerometer, a clinically validated physical activity monitor which was used to measure the levels of physical activity. Participants wore an accelerometer for 7 days during individual timepoint. Values at Baseline, Day 56 and Day 90 were the average values collected from accelerometer for 7 days after the Day -9, Day 56 and Day 90. Data from an accelerator was uploaded to a central site. Baseline was the average of the data collected from the 7-day period after dispensing of the device on Day -9. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day -9), Days 56 and 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    17 [184]
    17 [185]
    14 [186]
    17 [187]
    Units: Vector magnitude units per minute
    arithmetic mean (standard deviation)
        Day 56,n=17,14,14,17
    9.19 ( 82.596 )
    -4.83 ( 66.400 )
    56.42 ( 86.284 )
    71.98 ( 175.403 )
        Day 90,n=17,17,14,14
    -6.60 ( 65.648 )
    0.40 ( 64.670 )
    -3.73 ( 74.849 )
    42.36 ( 184.191 )
    Notes
    [184] - Analysis Population
    [185] - Analysis Population
    [186] - Analysis Population
    [187] - Analysis Population
    No statistical analyses for this end point

    Secondary: Number of participants with participant global impression of change (PGIC) score over time

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    End point title
    		 Number of participants with participant global impression of change (PGIC) score over time
    End point description
    Participant-reported response to treatment was assessed using the PGIC measure, a single item completed by participant to assess the participant’s impression of change in their disease severity since the beginning of the study. Responses to the PGIC question were on a 7 point Likert scale: Much Better, Better, Slightly Better, No Change, Slightly Worse, Worse, and Much Worse. Number of participants with PGIC score is presented by treatment group, visit and by 7 response categories. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Days 14, 28, 56 and 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [188]
    20 [189]
    23 [190]
    23 [191]
    Units: Participants
        Day 14, much worse,n=21,20,23,23
    0
    0
    0
    0
        Day 14, worse,n=21,20,23,23
    0
    0
    0
    1
        Day 14, slightly worse,n=21,20,23,23
    0
    1
    0
    0
        Day 14, no change,n=21,20,23,23
    6
    5
    9
    9
        Day 14, slightly better,n=21,20,23,23
    7
    7
    4
    4
        Day 14, better,n=21,20,23,23
    7
    5
    8
    7
        Day 14, much better,n=21,20,23,23
    1
    2
    2
    2
        Day 28, much worse,n=21,20,21,22
    0
    0
    0
    0
        Day 28, worse,n=21,20,21,22
    0
    0
    0
    0
        Day 28, slightly worse,n=21,20,21,22
    1
    2
    0
    0
        Day 28, no change,n=21,20,21,22
    3
    6
    4
    6
        Day 28, slightly better,n=21,20,21,22
    9
    6
    10
    7
        Day 28, better,n=21,20,21,22
    5
    6
    5
    7
        Day 28, much better,n=21,20,21,22
    3
    0
    2
    2
        Day 56, much worse,n=21,19,21,21
    0
    0
    0
    0
        Day 56, worse,n=21,19,21,21
    0
    0
    0
    0
        Day 56, slightly worse,n=21,19,21,21
    1
    3
    1
    4
        Day 56, no change,n=21,19,21,21
    2
    5
    4
    5
        Day 56, slightly better,n=21,19,21,21
    6
    4
    7
    5
        Day 56, better,n=21,19,21,21
    10
    6
    8
    5
        Day 56, much better,n=21,19,21,21
    2
    1
    1
    2
        Day 90, much worse,n=21,18,18,20
    0
    0
    0
    0
        Day 90, worse,n=21,18,18,20
    0
    1
    0
    0
        Day 90, slightly worse,n=21,18,18,20
    1
    0
    0
    0
        Day 90, no change,n=21,18,18,20
    9
    8
    5
    6
        Day 90, slightly better,n=21,18,18,20
    7
    3
    9
    9
        Day 90, better,n=21,18,18,20
    3
    4
    4
    4
        Day 90, much better,n=21,18,18,20
    1
    2
    0
    1
    Notes
    [188] - Analysis Population
    [189] - Analysis Population
    [190] - Analysis Population
    [191] - Analysis Population
    No statistical analyses for this end point

    Secondary: Number of participants with participant global rating of severity (PGRS) score over time

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    End point title
    		 Number of participants with participant global rating of severity (PGRS) score over time
    End point description
    PGRS is a single global question and was asked to participants to rate their COPD severity on a four point scale ranging from 1 to 4 (1=mild, 2=moderate, 3=severe, 4=very severe). Number of participants with PGRS score ranging from mild to very severe are presented over time. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Days 1 and 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [192]
    20 [193]
    23 [194]
    23 [195]
    Units: Participants
        Day 1, mild,n=21,20,23,23
    2
    0
    0
    2
        Day 1, moderate,n=21,20,23,23
    9
    13
    11
    12
        Day 1, severe,n=21,20,23,23
    8
    7
    12
    8
        Day 1, very severe,n=21,20,23,23
    2
    0
    0
    1
        Day 90, mild,n=21,18,18,20
    4
    4
    1
    5
        Day 90, moderate,n=21,18,18,20
    9
    7
    9
    2
        Day 90, severe,n=21,18,18,20
    6
    6
    8
    12
        Day 90, very severe,n=21,18,18,20
    2
    1
    0
    1
    Notes
    [192] - Analysis Population
    [193] - Analysis Population
    [194] - Analysis Population
    [195] - Analysis Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in St. George respiratory questionnaire (SGRQ) for COPD (SGRQ-c) total score

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    End point title
    		 Change from Baseline in St. George respiratory questionnaire (SGRQ) for COPD (SGRQ-c) total score
    End point description
    SGRQ-c is the COPD specific version of SGRQ. It consisted of 40 items in total, corresponding to 3 individual domains (components): symptoms, activity and impact, with different components carrying a different weighting. Component scores were calculated by summing the weights from all positive items in that component, dividing by the sum of maximum possible weights for all items in that component, and multiplying this number by 100. Total score was calculated by summing the weight to all the positive responses in each component. Total score has the range from 0 to 100. Higher scores indicated more severe disease impact. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using ANCOVA model. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [196]
    17 [197]
    18 [198]
    20 [199]
    Units: Scores on a scale
        least squares mean (standard error)
    -3.9 ( 1.71 )
    -0.9 ( 1.90 )
    -1.7 ( 1.87 )
    0.4 ( 1.77 )
    Notes
    [196] - Analysis Population
    [197] - Analysis Population
    [198] - Analysis Population
    [199] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by ANCOVA model with Baseline total score as the covariate adjusting for the treatment.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Least Square Means
    Point estimate
    3
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 7.4
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by ANCOVA model with Baseline total score as the covariate adjusting for the treatment.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Least Square Means
    Point estimate
    2.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -2.3
         upper limit
    		 6.5

    Secondary: Change from Baseline in SGRQ-c symptoms score

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    End point title
    		 Change from Baseline in SGRQ-c symptoms score
    End point description
    SGRQ-c is the COPD specific version of SGRQ. It consisted of 40 items in total, corresponding to 3 individual domains (components): symptoms, activity and impact, with different components carrying a different weighting. Component scores were calculated by summing the weights from all positive items in that component, dividing by the sum of maximum possible weights for all items in that component, and multiplying this number by 100. Symptoms component consisted of questions 1 to 7 in Part 1. Symptoms score has the range from 0 to 100. Higher scores indicated more severe disease impact. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using ANCOVA model. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [200]
    17 [201]
    18 [202]
    20 [203]
    Units: Scores on a scale
        least squares mean (standard error)
    -4.0 ( 2.95 )
    -1.4 ( 3.29 )
    -3.5 ( 3.38 )
    -4.0 ( 3.20 )
    Notes
    [200] - Analysis Population
    [201] - Analysis Population
    [202] - Analysis Population
    [203] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by ANCOVA model with Baseline symptoms score as the covariate adjusting for the treatment.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Least Square Means
    Point estimate
    2.6
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -5
         upper limit
    		 10.1
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by ANCOVA model with Baseline symptoms score as the covariate adjusting for the treatment.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Least Square Means
    Point estimate
    -0.5
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -8.4
         upper limit
    		 7.5

    Secondary: Change from Baseline in SGRQ-c activity score

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    End point title
    		 Change from Baseline in SGRQ-c activity score
    End point description
    SGRQ-c is the COPD specific version of SGRQ. It consisted of 40 items in total, corresponding to 3 individual domains (components): symptoms, activity and impact, with different components carrying a different weighting. Component scores were calculated by summing the weights from all positive items in that component, dividing by the sum of maximum possible weights for all items in that component, and multiplying this number by 100. Activity component consisted of questions 9 and 12 in Part 2 of the questionnaire. Activity score has the range from 0 to 100. Higher scores indicated more severe disease impact. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using ANCOVA model. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [204]
    17 [205]
    18 [206]
    20 [207]
    Units: Scores on a scale
        least squares mean (standard error)
    -5.4 ( 2.00 )
    -3.4 ( 2.23 )
    1.2 ( 2.57 )
    1.6 ( 2.44 )
    Notes
    [204] - Analysis Population
    [205] - Analysis Population
    [206] - Analysis Population
    [207] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by ANCOVA model with Baseline activity score as the covariate adjusting for the treatment.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Least Square Means
    Point estimate
    2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -3.2
         upper limit
    		 7.1
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by ANCOVA model with Baseline activity score as the covariate adjusting for the treatment.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Least Square Means
    Point estimate
    0.5
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -5.6
         upper limit
    		 6.5

    Secondary: Change from Baseline in SGRQ-c impact score

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    End point title
    		 Change from Baseline in SGRQ-c impact score
    End point description
    SGRQ-c is the COPD specific version of SGRQ. It consisted of 40 items in total, corresponding to 3 individual domains (components): symptoms, activity and impact, with different components carrying a different weighting. Component scores were calculated by summing the weights from all positive items in that component, dividing by the sum of maximum possible weights for all items in that component, and multiplying this number by 100. Impact component consisted of questions 8, 10, 11, 13, 14 in Part 2 of the questionnaire. Impact score has the range from 0 to 100. Higher scores indicated more severe disease impact. Day 1 (Pre-dose) was considered as a Baseline. Analysis was performed using ANCOVA model. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Day 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [208]
    17 [209]
    18 [210]
    20 [211]
    Units: Scores on a scale
        least squares mean (standard error)
    -2.8 ( 2.03 )
    0.6 ( 2.25 )
    -2.7 ( 1.76 )
    0.8 ( 1.67 )
    Notes
    [208] - Analysis Population
    [209] - Analysis Population
    [210] - Analysis Population
    [211] - Analysis Population
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by ANCOVA model with Baseline impact score as the covariate adjusting for the treatment.
    Comparison groups
    Placebo- Female Participants v GSK2881078 1.0 mg- Female Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Least Square Means
    Point estimate
    3.4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -1.7
         upper limit
    		 8.6
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    Analysis was performed by ANCOVA model with Baseline impact score as the covariate adjusting for the treatment.
    Comparison groups
    Placebo- Male Participants v GSK2881078 2.0 mg- Male Participants
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Least Square Means
    Point estimate
    3.5
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 7.7

    Secondary: Change from Baseline in forced expiratory volume in 1 second (FEV1)

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    End point title
    		 Change from Baseline in forced expiratory volume in 1 second (FEV1)
    End point description
    FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 measurements were collected using a spirometer. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Days 56 and 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [212]
    19 [213]
    21 [214]
    21 [215]
    Units: Liters
    arithmetic mean (standard deviation)
        Day 56,n=21,19,21,21
    -0.000 ( 0.0918 )
    -0.028 ( 0.0747 )
    0.012 ( 0.1342 )
    -0.016 ( 0.2377 )
        Day 90,n=20,18,18,20
    0.002 ( 0.0970 )
    -0.024 ( 0.0833 )
    0.050 ( 0.1130 )
    0.007 ( 0.2208 )
    Notes
    [212] - Analysis Population
    [213] - Analysis Population
    [214] - Analysis Population
    [215] - Analysis Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in sniff nasal inspiratory pressure (SnIP)

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    End point title
    		 Change from Baseline in sniff nasal inspiratory pressure (SnIP)
    End point description
    A bung size-specific to the participant was placed in the nostril deemed to be most patent by the investigator. The participant was asked to make a maximum voluntary sniff effort via a peak flow meter and the greatest effort from 10 repeat measurements were recorded. SnIP was measured in centimeter of water (cm H2O). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated as post-dose visit value minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1, Pre-dose), Days 56 and 90
    End point values
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [216]
    19 [217]
    21 [218]
    21 [219]
    Units: centimeter of water
    arithmetic mean (standard deviation)
        Day 56,n=21,19,21,21
    -6.0 ( 11.20 )
    3.4 ( 14.14 )
    0.7 ( 17.82 )
    -0.8 ( 15.51 )
        Day 90,n=20,18,18,20
    -0.7 ( 8.55 )
    -0.4 ( 11.34 )
    -1.2 ( 15.21 )
    2.5 ( 21.39 )
    Notes
    [216] - Analysis Population
    [217] - Analysis Population
    [218] - Analysis Population
    [219] - Analysis Population
    No statistical analyses for this end point

    Secondary: Clearance (CL) of GSK2881078 following oral dose in participants

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    End point title
    		 Clearance (CL) of GSK2881078 following oral dose in participants [220]
    End point description
    Blood samples were collected at designated timepoints. Pharmacokinetics (PK) parameters of GSK2881078 were calculated using non-compartmental methods. Pharmacokinetic Population comprised of participants in the ‘All Participants (all randomized participants who received at least one dose of study medication)’’ Population for whom a PK sample was obtained and analyzed for GSK2881078.
    End point type
    Secondary
    End point timeframe
    Day 14 (Pre-dose), Day 28 (Pre-dose and at 1 to 4 hours Post-dose), Day 56 (at 5 to 8 hours Post-dose), Day 90 (Pre-dose)
    Notes
    [220] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 GSK2881078 1.0 mg- Female Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [221]
    24 [222]
    Units: Liters per hour
        geometric mean (geometric coefficient of variation)
    0.393 ( 59.5 )
    0.476 ( 44.0 )
    Notes
    [221] - Pharmacokinetic Population
    [222] - Pharmacokinetic Population
    No statistical analyses for this end point

    Secondary: Volume of distribution at steady state (Vss) of GSK2881078 following oral dose in participants

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    End point title
    		 Volume of distribution at steady state (Vss) of GSK2881078 following oral dose in participants [223]
    End point description
    Blood samples were collected at designated timepoints. PK parameters of GSK2881078 were calculated using non-compartmental methods.
    End point type
    Secondary
    End point timeframe
    Day 14 (Pre-dose), Day 28 (Pre-dose and at 1 to 4 hours Post-dose), Day 56 (at 5 to 8 hours Post-dose), Day 90 (Pre-dose)
    Notes
    [223] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period.
    End point values
    		 GSK2881078 1.0 mg- Female Participants GSK2881078 2.0 mg- Male Participants
    Number of subjects analysed
    21 [224]
    24 [225]
    Units: Liters
        geometric mean (geometric coefficient of variation)
    39.4 ( 16.3 )
    48.3 ( 29.8 )
    Notes
    [224] - Pharmacokinetic Population
    [225] - Pharmacokinetic Population
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment until up to Day 132
    Adverse event reporting additional description
    SAEs and non-serious AEs were reported for the Safety Population which comprised of all randomized participants who received at least one dose of study medication. This population was based on the treatment the participant received.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Placebo- Female Participants
    Reporting group description
    		 Post-menopausal female participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks

    Reporting group title
    GSK2881078 1.0 mg- Female Participants
    Reporting group description
    		 Post-menopausal female participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 of a unit dose strength 0.5 milligram (mg) once daily over 13 weeks

    Reporting group title
    Placebo- Male Participants
    Reporting group description
    		 Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks

    Reporting group title
    GSK2881078 2.0 mg- Male Participants
    Reporting group description
    		 Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 of a unit dose strength 1.0 mg once daily over 13 weeks

    Serious adverse events
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 23 (4.35%)
    2 / 24 (8.33%)
    2 / 24 (8.33%)
    0 / 25 (0.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial infarction
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Diverticulitis
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Placebo- Female Participants GSK2881078 1.0 mg- Female Participants Placebo- Male Participants GSK2881078 2.0 mg- Male Participants
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    15 / 23 (65.22%)
    18 / 24 (75.00%)
    13 / 24 (54.17%)
    17 / 25 (68.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adrenal adenoma
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    1
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    2 / 24 (8.33%)
    0 / 25 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Haematoma
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Hypotension
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    2 / 24 (8.33%)
    0 / 25 (0.00%)
         occurrences all number
    0
    0
    2
    0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    1
    1
    Fatigue
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    0 / 24 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    1
    0
    0
    1
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    6 / 23 (26.09%)
    7 / 24 (29.17%)
    2 / 24 (8.33%)
    3 / 25 (12.00%)
         occurrences all number
    6
    8
    2
    4
    Epistaxis
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    2 / 24 (8.33%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    2
    1
    Dyspnoea
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Pulmonary mass
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    1
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    1
    0
    2
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    1
    0
    1
    Blood 25-hydroxycholecalciferol decreased
         subjects affected / exposed
    0 / 23 (0.00%)
    2 / 24 (8.33%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Low density lipoprotein increased
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    1
    0
    1
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    3 / 23 (13.04%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    3
    1
    0
    0
    Muscle strain
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    1 / 24 (4.17%)
    0 / 25 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 23 (0.00%)
    2 / 24 (8.33%)
    0 / 24 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    2
    0
    2
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    1 / 25 (4.00%)
         occurrences all number
    1
    0
    1
    1
    Abdominal pain upper
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    1 / 24 (4.17%)
    0 / 25 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Constipation
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    1
    0
    1
    Nausea
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    1
    1
    0
    0
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    1
    1
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    1
    0
    1
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    0
    1
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 23 (0.00%)
    3 / 24 (12.50%)
    2 / 24 (8.33%)
    2 / 25 (8.00%)
         occurrences all number
    0
    5
    2
    2
    Muscle spasms
         subjects affected / exposed
    1 / 23 (4.35%)
    2 / 24 (8.33%)
    0 / 24 (0.00%)
    3 / 25 (12.00%)
         occurrences all number
    1
    2
    0
    3
    Back pain
         subjects affected / exposed
    0 / 23 (0.00%)
    3 / 24 (12.50%)
    0 / 24 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    3
    0
    3
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    1
    0
    2
    Musculoskeletal Pain
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    1
    1
    0
    1
    Neck pain
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    0 / 25 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    5 / 23 (21.74%)
    2 / 24 (8.33%)
    1 / 24 (4.17%)
    1 / 25 (4.00%)
         occurrences all number
    5
    3
    1
    2
    Urinary tract infection
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 24 (4.17%)
    0 / 24 (0.00%)
    1 / 25 (4.00%)
         occurrences all number
    1
    1
    0
    2
    Sinusitis
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    1
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 24 (0.00%)
    1 / 24 (4.17%)
    1 / 25 (4.00%)
         occurrences all number
    0
    0
    1
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    19 May 2017
    Amendment 01: Removal of reference to measurement of lumbar bone density in the risk mitigation strategy for bone effects in section: risk assessment; removal of reference to measurement of lumbar bone density in section: dual-energy X-ray absorptiometry (DXA)
    22 Aug 2017
    Amendment 02: Removal of the stair climb test as a secondary endpoint in the study; removal of the requirements for vitamin D deficiency as an exclusion criteria; removal of reference to an independent monitoring committee; deletion of erroneous text describing supply of study drug to the participant at Day 90; reference to whole body multiple resonance imaging (MRI) removed and replaced with ‘cardiac and liver MRI (additionally prostate MRI in males) for clarity; edits to clarify that only the safety assessments at the follow-up visit would be conducted in case of withdrawal from the study; wording to clarify that any chronic obstructive pulmonary disease exacerbation that requires steroid use requires participants to withdraw from the study; clarification in the duration of necessary contraception use following participation in the study.
    11 Oct 2017
    Amendment 03: Removal of inspiratory capacity as an endpoint, as well as peak oxygen uptake measurements during the shuttle walk tests; previous guidance prohibiting concomitant use of cytochrome P-450 isoenzyme 3A4 (CYP3A4) inhibitors was removed.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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