Study to Evaluate the Safety and Efficacy of 13 Weeks of the Selective Androgen Receptor Modulator (SARM) GSK2881078 in Chronic Obstructive Pulmonary Disease (COPD)

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03359473
• Collaborator: Parexel (Industry)
• Enrollment: 97
• Locations: 11
• Arms: 4
• Actual Duration (Months): 20.7
• Patients Per Site: 8.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Impaired physical function and muscle dysfunction are a major consequence of COPD, which may be associated with increased mortality, poor quality of life and increased health care use. This is a randomized, placebo-controlled, double-blind, parallel group study to evaluate the safety and tolerability of GSK2881078, an SARM over 13 weeks of dosing in older male subjects and post-menopausal female subjects with COPD and muscle weakness. This study will also assess the effect of GSK2881078 on physical strength and function after 13 weeks of treatment. Approximately 100 subjects with COPD and muscle weakness will be randomized into two cohorts of 50 male subjects and 50 female subjects. Within each cohort, subjects will be randomized to receive GSK2881078 or placebo in a ratio of 1:1. All subjects will participate in a standardized home exercise program, which will consist of daily walking, along with several resistance or weight-bearing exercises, such as bicep curls, upright rows, step ups and a sit-to-stand maneuver. The study will consist of a screening/Baseline period of up to 30 days, a 13-week treatment period and a post-treatment follow-up period of 6 weeks.

Condition or Disease	Intervention/Treatment	Phase
Cachexia	Drug: GSK2881078; Drug: Matching Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 97 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Study treatment will consist of two dosing cohorts: Cohort 1 will comprise of male subjects randomized to receive either placebo or 2 milligrams (mg) of GSK2881078 and Cohort 2 will comprise of post-menopausal female subjects randomized to receive either placebo or 1 mg of GSK2881078.Study treatment will consist of two dosing cohorts: Cohort 1 will comprise of male subjects randomized to receive either placebo or 2 milligrams (mg) of GSK2881078 and Cohort 2 will comprise of post-menopausal female subjects randomized to receive either placebo or 1 mg of GSK2881078.
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind (Sponsor Unblind), Placebo-controlled, Multi-centred 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
• Actual Study Start Date: Feb 28, 2018
• Actual Primary Completion Date: Nov 19, 2019
• Actual Study Completion Date: Nov 19, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Male subjects receiving GSK2881078-Cohort 1 Male subjects between the age of 50 and 75 years will be administered GSK2881078 at a dose of 2 mg once daily by the oral route.	Drug: GSK2881078; GSK2881078 will be available as capsules for oral administration. GSK2881078 will be administered once daily by the oral route at a dose of 1 mg and 2mg to post-menopausal female subjects and male subjects, respectively.
Placebo Comparator: Male subjects receiving Placebo-Cohort 1 Male subjects between the age of 50 and 75 years will be administered GSK2881078 matching placebo once daily by the oral route.	Drug: Matching Placebo; Subjects will be administered two capsules of GSK2881078 matching placebo once daily by the oral route.
Experimental: Female subjects receiving GSK2881078-Cohort 2 Post-menopausal female subjects between the age of 50 and 75 years will be administered GSK2881078 at a dose of 1 mg once daily by the oral route.	Drug: GSK2881078; GSK2881078 will be available as capsules for oral administration. GSK2881078 will be administered once daily by the oral route at a dose of 1 mg and 2mg to post-menopausal female subjects and male subjects, respectively.
Placebo Comparator: Female subjects receiving Placebo-Cohort 2 Post-menopausal female subjects between the age of 50 and 75 years will be administered GSK2881078 matching placebo once daily by the oral route.	Drug: Matching Placebo; Subjects will be administered two capsules of GSK2881078 matching placebo once daily by the oral route.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [Baseline (Day 1, Pre-dose), Days 14, 28, 56 and 90]

   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.

2. Change From Baseline in Heart Rate [Baseline (Day 1, Pre-dose), Days 14, 28, 56 and 90]

   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.

3. 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) [Baseline (Day 1, Pre-dose), Days 14, 28, 56 and 90]

   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.

4. Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters [Baseline (Day 1, Pre-dose) and up to Day 132]

   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.

5. Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters [Baseline (Day 1, Pre-dose) and up to Day 132]

   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.

6. Change From Baseline in Urinalysis Parameter; Specific Gravity: Placebo-Female Participants [Baseline (Day 1, Pre-dose), Days 28, 56 and 90]

   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.

7. Change From Baseline in Urinalysis Parameter; Specific Gravity: GSK2881078 1.0 mg- Female Participants [Baseline (Day 1, Pre-dose), Days 14 and 90]

   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.

8. Change From Baseline in Urinalysis Parameter; Specific Gravity: Male Participants [Baseline (Day 1, Pre-dose), Days 28 and 90]

   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.

9. Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH): Placebo- Female Participants [Baseline (Day 1, Pre-dose), Days 28, 56 and 90]

   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.

10. Change From Baseline in Urinalysis Parameter; pH: GSK2881078 1.0 mg- Female Participants [Baseline (Day 1, Pre-dose), Days 14 and 90]

    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.

11. Change From Baseline in Urinalysis Parameter; pH: Male Participants [Baseline (Day 1, Pre-dose), Days 28 and 90]

    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.

12. Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline [Baseline (Day 1, Pre-dose) and up to Day 132]

    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.

13. Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events [Up to Day 132]

    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.

14. Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 28 [Baseline (Day 1, Pre-dose), Day 28]

    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 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.

15. Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 56 [Baseline (Day 1, Pre-dose), Day 56]

    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.

16. Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 90 [Baseline (Day 1, Pre-dose), Day 90]

    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.

17. Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 28 [Baseline (Day 1, Pre-dose), Day 28]

    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.

18. Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 56 [Baseline (Day 1, Pre-dose), Day 56]

    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.

19. Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 90 [Baseline (Day 1, Pre-dose), Day 90]

    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.

Secondary Outcome Measures

1. Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 28 [Baseline (Day 1, Pre-dose), Day 28]

   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.

2. Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 56 [Baseline (Day 1, Pre-dose), Day 56]

   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.

3. Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 90 [Baseline (Day 1, Pre-dose), Day 90]

   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.

4. Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 28 [Baseline (Day 1, Pre-dose), Day 28]

   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.

5. Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 56 [Baseline (Day 1, Pre-dose), Day 56]

   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.

6. Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 90 [Baseline (Day 1, Pre-dose), Day 90]

   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.

7. Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 28 [Baseline (Day 1, Pre-dose), Day 28]

   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.

8. Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 56 [Baseline (Day 1, Pre-dose), Day 56]

   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.

9. Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 90 [Baseline (Day 1, Pre-dose), Day 90]

   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.

10. Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 28 [Baseline (Day 1, Pre-dose), Day 28]

    '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.

11. Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 56 [Baseline (Day 1, Pre-dose), Day 56]

    '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.

12. Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 90 [Baseline (Day 1, Pre-dose), Day 90]

    '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.

13. Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 28 [Baseline (Day 1, Pre-dose), Day 28]

    ''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.

14. Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 56 [Baseline (Day 1, Pre-dose), Day 56]

    '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.

15. Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 90 [Baseline (Day 1, Pre-dose), Day 90]

    '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.

16. Change From Baseline in Constant Work Rate (CWR) Duration From Endurance Shuttle Walking Test [Baseline (Day 1, Pre-dose), Day 90]

    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.

17. Change From Baseline in Peak Performance From Incremental Shuttle Walking Test [Baseline (Highest non-missing pre-dose assessment from Day-9 and Day 1), Day 90]

    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.

18. Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Score at Day 56 [Baseline (Day 1, Pre-dose), Day 56]

    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.

19. Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Score at Day 90 [Baseline (Day 1, Pre-dose), Day 90]

    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.

20. Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Difficulty Score at Day 56 [Baseline (Day -9), Day 56]

    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 for averaged weekly difficulty score.

21. Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Difficulty Score at Day 90 [Baseline (Day -9), Day 90]

    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 for averaged weekly difficulty score.

22. Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Amount Score at Day 56 [Baseline (Day -9), Day 56]

    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 for averaged weekly amount score.

23. Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Amount Score at Day 90 [Baseline (Day -9), Day 90]

    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 for averaged weekly amount score.

24. Change From Baseline in Participant Reported Outcome (PRO)Active Total Score at Day 56 [Baseline (Day -9), Day 56]

    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 scale for each domain. The 'total score' was obtained by calculating the average between two domains. Total score has the range 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. Adjusted means and SE are presented

25. Change From Baseline in Participant Reported Outcome (PRO)Active Total Score at Day 90 [Baseline (Day -9), Day 90]

    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 scale for each domain. The 'total score' was obtained by calculating the average between two domains. Total score has the range 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. Adjusted means and SE are presented.

26. Change From Baseline in Steps Per Day (Physical Activity Measure) as Assessed Via an Accelerometer [Baseline (Day -9), Days 56 and 90]

    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.

27. Change From Baseline in Vector Magnitude Unit Per Wear Time (Physical Activity Measure) as Assessed Via an Accelerometer [Baseline (Day -9), Days 56 and 90]

    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.

28. Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time [Days 14, 28, 56 and 90]

    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.

29. Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time [Days 1 and 90]

    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.

30. Change From Baseline in St. George Respiratory Questionnaire (SGRQ) for COPD (SGRQ-c) Total Score [Baseline (Day 1, Pre-dose), Day 90]

    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.

31. Change From Baseline in SGRQ-c Symptoms Score [Baseline (Day 1, Pre-dose), Day 90]

    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.

32. Change From Baseline in SGRQ-c Activity Score [Baseline (Day 1, Pre-dose), Day 90]

    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.

33. Change From Baseline in SGRQ-c Impact Score [Baseline (Day 1, Pre-dose), Day 90]

    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.

34. Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) [Baseline (Day 1, Pre-dose), Days 56 and 90]

    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.

35. Change From Baseline in Sniff Nasal Inspiratory Pressure (SnIP) [Baseline (Day 1, Pre-dose), Days 56 and 90]

    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.

36. Clearance (CL) of GSK2881078 Following Oral Dose in Participants [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)]

    Blood samples were collected at designated timepoints. Pharmacokinetics (PK) parameters of GSK2881078 were calculated using non-compartmental methods.

37. Volume of Distribution at Steady State (Vss) of GSK2881078 Following Oral Dose in Participants [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)]

    Blood samples were collected at designated timepoints. PK parameters of GSK2881078 were calculated using non-compartmental methods.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject must be 50 to 75 years of age inclusive, at the time of signing the informed consent.

• Male and/or female subjects will be included. a) A male subject with a partner who is a woman of child bearing potential (WOCPB) must agree to use contraception during the treatment period and until at least 5 half-lives of study medication have passed after the last ingested dose [125 days, corresponding to time needed to eliminate study treatment for both genotoxic and teratogenic study treatments plus an additional 90 days (a spermatogenesis cycle) for study treatments with genotoxic potential] after the last dose of study treatment and refrain from donating sperm during this period.

1. A female subject is eligible to participate if she is post-menopausal and not a WOCBP.

• Confirmed diagnosis of COPD in accordance with the American Thoracic Society (ATS)/European Respiratory Society (ERS) criteria with a post-bronchodilator FEV1/forced vital capacity (FVC) <0.70 and 30% <= FEV1% predicted <=65% of predicted normal value calculated at Screen using the Quanjer reference equation.

• SPPB with ALL of the following: Timed chair stand score >=1 and <=3; No score of "0" on any component of the SPPB (that is, gait speed, balance, or timed chair stand).

• Body Mass Index (BMI) within the range 18-32 kilogram per meter square (kg/m^2) (inclusive), where BMI = (weight in kg)/(height in meters)^2

• Current smokers or former smokers with a cigarette smoking history of >=10 pack years (1 pack year =20 cigarettes smoked per day for 1 year or equivalent). Former smokers are defined as those who have stopped smoking for at least 6 months prior to Baseline.

• Subjects must be able to read and write in the language used for the provided electronic diary and be able to operate an electronic device to a level that allows them to complete an electronic diary on a daily basis.

• Subjects participating in a structured exercise program must be willing to convert their current exercise program to the home exercise program used in this study.

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol.

Exclusion Criteria:

• Subjects with a history of myocardial infarction, angina, congestive heart failure exacerbation, hospitalization for cardiac etiology, stroke or transient ischemic attack in the past 12 months.

• Neurologic, musculoskeletal, osteoarthritis, or any other condition that in the opinion of the investigator limits subject's ability to complete study physical assessments.

• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

• Subjects with a history of cholecystectomy.

• Subjects with a history of malignancy that is not in complete remission for at least 2 years or 1 year for non-melanoma skin carcinoma.

• Subjects with a family history of early onset prostate cancer or familial prostate cancer (multiple family members).

• Diseases known to cause malabsorption of protein or energy, such as inflammatory bowel disease, celiac disease, pancreatic insufficiency, etc.

• Current or planned administration of cholestyramine or strong oral or injectable cytochrome P-450 isoenzyme 3A4 (CYP3A4) inducers.

• Current or planned use of any prescription drugs known to affect muscle mass, including androgen supplements, anti-androgens (such as luteinizing hormone-releasing hormone [LHRH] agonists), anti-estrogens (tamoxifen, etc.), recombinant growth hormone, megesterol, etc.

• Use of oral steroids concurrently or within 4 weeks preceding the screening visit.

• The subject has participated in a clinical trial and has received an investigational product within the following time-period prior to randomization in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

• Subjects with values outside the specified ranges for the following Key Clinical Laboratory Tests must be excluded from the study: a) Renal function: Glomerular Filtration Rate (GFR) <30 milliliter per minute per 1.73 meter square (mL/min/1.73 m^2). Subjects receiving dialysis are excluded from this study. b) Metabolic-glycated hemoglobin (HbA1c) >7.5%. c) ALT >2 times upper limit of normal (ULN) and bilirubin

1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). d) Hematology - Hemoglobin <10.0 grams per deciliter (g/dL) at screening. e) Prostate Specific Antigen (PSA) >4.0 nanograms per milliliter (ng/mL).

• Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.

• QT interval corrected for heart rate by Bazett's formula (QTcB) or QT interval corrected for heart rate by Fridericia's formula (QTcF) >450 milliseconds (msec) or QT interval corrected for heart rate (QTc) >480 msec in subjects with Bundle Branch Block based on a single ECG.

• A positive test for human immunodeficiency virus (HIV) antibody.

• More than two moderate/severe COPD exacerbations within the past year. Exacerbation is defined as worsening of two or more of the following major symptoms: dyspnea, sputum volume, sputum purulence OR worsening of any one major symptom together with at least one of the following additional symptoms: sore throat, colds (nasal discharge and/or nasal congestion), fever >37.5 degree Celsius without any explained cause, increased cough, increased wheeze. A moderate exacerbation is defined as an exacerbation that requires treatment with antibiotics and/or oral steroids. A severe exacerbation is defined as an event that is additionally associated with hospitalization or emergency room visit.

• Any moderate/severe COPD exacerbation in the 4 weeks preceding the screening visit.

• Subjects on long-term oxygen therapy (LTOT), defined as prescribed continuous oxygen use for >14 hours/day.

• Clinically diagnosed history of drug or alcohol abuse within 5 years prior to randomization.

• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation.

• Participation in a formal pulmonary rehabilitation exercise program outside or inside the home, either currently or completed within the previous 6 months.

• For subjects who opt to have magnetic resonance imaging (MRI) at participating study sites, there must be no contraindications to MRI, for example known claustrophobia or a pacemaker. Specific MRI contraindications will be determined by the type of MRI scanner available at each site and study personnel should confirm local eligibility requirements.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Torrance	California	United States	90502
2	GSK Investigational Site	Jacksonville	Florida	United States	32216
3	GSK Investigational Site	High Point	North Carolina	United States	27262
4	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19140
5	GSK Investigational Site	Spartanburg	South Carolina	United States	29303
6	GSK Investigational Site	Frankfurt	Hessen	Germany	60596
7	GSK Investigational Site	Grosshansdorf	Schleswig-Holstein	Germany	22927
8	GSK Investigational Site	Leicester	Leicestershire	United Kingdom	LE3 9QP
9	GSK Investigational Site	Harefield	Middlesex	United Kingdom	UB9 6JH
10	GSK Investigational Site	London, Greater London		United Kingdom	SE1 7EH
11	GSK Investigational Site	London		United Kingdom	SW3 6HP

Sponsors and Collaborators

• GlaxoSmithKline
• Parexel

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Statistical Analysis Plan - Jan 9, 2020
• Study Protocol - Oct 11, 2017

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03359473
• Other Study ID Numbers: 200182; 2017-001148-37
• First Posted: Dec 2, 2017
• Last Update Posted: Jul 15, 2020
• Last Verified: Jun 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GlaxoSmithKline: GSK2881078; COPD; muscle weakness; post-menopausal; selective androgen receptor modulator
• Additional relevant MeSH terms: Muscle Weakness; Cachexia; GSK2881078

Study Results

Participant Flow

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 Detail	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.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Period Title: Overall Study
STARTED	23	24	24	25
COMPLETED	21	18	18	20
NOT COMPLETED	2	6	6	5

Baseline Characteristics

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants	Total
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.	Total of all reporting groups
Overall Participants	23	24	24	25	96
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	64.7 (7.16)	64.2 (7.93)	64.0 (7.27)	67.2 (6.08)	65.1 (7.14)
Sex: Female, Male (Count of Participants)
Female	23 100%	24 100%	0 0%	0 0%	47 49%
Male	0 0%	0 0%	24 100%	25 100%	49 51%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	0 0%	1 4.2%	2 8.3%	2 8%	5 5.2%
White-White/Caucasian/European Heritage	23 100%	23 95.8%	22 91.7%	23 92%	91 94.8%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
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.
Time Frame	Baseline (Day 1, Pre-dose), Days 14, 28, 56 and 90

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	22	23	23	24
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)

2. Primary Outcome

Title	Change From Baseline in Heart Rate
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.
Time Frame	Baseline (Day 1, Pre-dose), Days 14, 28, 56 and 90

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	22	23	23	24
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)

3. Primary Outcome

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)
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.
Time Frame	Baseline (Day 1, Pre-dose), Days 14, 28, 56 and 90

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	22	23	23	24
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)

4. Primary Outcome

Title	Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters
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.
Time Frame	Baseline (Day 1, Pre-dose) and up to Day 132

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	23	22	24	25
Hb, Anemia, increase to Grade 3	0 0%	0 0%	0 0%	0 0%
Hb, Anemia, increase to Grade 4	0 0%	0 0%	0 0%	0 0%
Hb, Hb increased, increase to Grade 3	0 0%	0 0%	0 0%	0 0%
Hb, Hb increased, increase to Grade 4	0 0%	0 0%	0 0%	0 0%
Lympho, Lymph count decreased, increase to Grade 3	0 0%	0 0%	0 0%	0 0%
Lympho, Lymph count decreased, increase to Grade 4	0 0%	0 0%	0 0%	0 0%
Lympho, Lymph count increased, increase to Grade 3	0 0%	0 0%	0 0%	0 0%
Lympho, Lymph count increased, increase to Grade 4	0 0%	0 0%	0 0%	0 0%
Neutro,Neutro count decreased,increase to Grade 3	0 0%	0 0%	0 0%	0 0%
Neutro,Neutro count decreased,increase to Grade 4	0 0%	0 0%	0 0%	0 0%
PC, PC decreased,increase to Grade 3	0 0%	0 0%	0 0%	0 0%
PC, PC decreased,increase to Grade 4	0 0%	0 0%	0 0%	0 0%
PC, PC increased,increase to Grade 3	0 0%	0 0%	0 0%	0 0%
PC, PC increased,increase to Grade 4	0 0%	0 0%	0 0%	0 0%

5. Primary Outcome

Title	Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters
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.
Time Frame	Baseline (Day 1, Pre-dose) and up to Day 132

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	23	22	24	25
ALT, ALT increased, increase to Grade 3	0 0%	1 4.2%	0 0%	1 4%
ALT, ALT increased, increase to Grade 4	0 0%	0 0%	0 0%	0 0%
ALP, ALP increased, increase to Grade 3	0 0%	0 0%	0 0%	0 0%
ALP, ALP increased, increase to Grade 4	0 0%	0 0%	0 0%	0 0%
AST, AST increased, increase to Grade 3	0 0%	0 0%	0 0%	0 0%
AST, AST increased, increase to Grade 4	0 0%	0 0%	0 0%	0 0%
Bil, Blood Bil increased, increase to Grade 3	0 0%	0 0%	0 0%	0 0%
Bil, Blood Bil increased, increase to Grade 4	0 0%	0 0%	0 0%	0 0%
Ca, Hyper,increase to Grade 3	0 0%	0 0%	0 0%	0 0%
Ca, Hyper,increase to Grade 4	0 0%	0 0%	0 0%	0 0%
Ca, Hypo,increase to Grade 3	0 0%	0 0%	0 0%	0 0%
Ca, Hypo,increase to Grade 4	0 0%	0 0%	0 0%	0 0%
Chol, Chol high,increase to Grade 3	0 0%	0 0%	0 0%	0 0%
Chol, Chol high,increase to Grade 4	0 0%	0 0%	0 0%	0 0%
Creat, Creat increased,increase to Grade 3	0 0%	0 0%	0 0%	0 0%
Creat, Creat increased,increase to Grade 4	0 0%	0 0%	0 0%	0 0%
Gl, Hyper,increase to Grade 3	0 0%	0 0%	0 0%	1 4%
Gl, Hyper,increase to Grade 4	0 0%	0 0%	0 0%	0 0%
Gl, Hypo,increase to Grade 3	0 0%	0 0%	0 0%	0 0%
Gl, Hypo,increase to Grade 4	0 0%	0 0%	0 0%	0 0%
Phos, Hyper,increase to Grade 3	0 0%	0 0%	0 0%	0 0%
Phos, Hyper,increase to Grade 4	0 0%	0 0%	0 0%	0 0%
Phos, Hypo,increase to Grade 3	0 0%	0 0%	0 0%	0 0%
Phos, Hypo,increase to Grade 4	0 0%	0 0%	0 0%	0 0%
Pot, Hyper,increase to Grade 3	0 0%	0 0%	0 0%	0 0%
Pot, Hyper,increase to Grade 4	0 0%	0 0%	0 0%	0 0%
Pot, Hypo,increase to Grade 3	0 0%	0 0%	1 4.2%	0 0%
Pot, Hypo,increase to Grade 4	0 0%	0 0%	0 0%	0 0%
Sod, Hyper,increase to Grade 3	0 0%	0 0%	0 0%	0 0%
Sod, Hyper,increase to Grade 4	0 0%	0 0%	0 0%	0 0%
Sod, Hypo,increase to Grade 3	2 8.7%	0 0%	0 0%	0 0%
Sod, Hypo,increase to Grade 4	0 0%	0 0%	0 0%	0 0%

6. Primary Outcome

Title	Change From Baseline in Urinalysis Parameter; Specific Gravity: Placebo-Female Participants
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.
Time Frame	Baseline (Day 1, Pre-dose), Days 28, 56 and 90

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Placebo- Female Participants
Arm/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.
Measure Participants	21
Day 28,n=1	0.0030 (NA)
Day 56,n=1	0.0020 (NA)
Day 90,n=21	-0.0006 (0.00612)

7. Primary Outcome

Title	Change From Baseline in Urinalysis Parameter; Specific Gravity: GSK2881078 1.0 mg- Female Participants
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.
Time Frame	Baseline (Day 1, Pre-dose), Days 14 and 90

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	GSK2881078 1.0 mg- Female Participants
Arm/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.
Measure Participants	18
Day 14,n=1	0.000 (NA)
Day 90,n=18	0.0049 (0.00711)

8. Primary Outcome

Title	Change From Baseline in Urinalysis Parameter; Specific Gravity: Male Participants
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.
Time Frame	Baseline (Day 1, Pre-dose), Days 28 and 90

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/Group Description	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	19	20
Day 28,n=1,1	-0.0080 (NA)	0.0040 (NA)
Day 90,n=19,20	0.0017 (0.00870)	0.0018 (0.00610)

9. Primary Outcome

Title	Change From Baseline in Urinalysis Parameter; Potential of Hydrogen (pH): Placebo- Female Participants
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.
Time Frame	Baseline (Day 1, Pre-dose), Days 28, 56 and 90

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Placebo- Female Participants
Arm/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.
Measure Participants	21
Day 28,n=1	0.0000 (NA)
Day 56,n=1	-0.5000 (NA)
Day 90,n=21	0.0000 (0.80623)

10. Primary Outcome

Title	Change From Baseline in Urinalysis Parameter; pH: GSK2881078 1.0 mg- Female Participants
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.
Time Frame	Baseline (Day 1, Pre-dose), Days 14 and 90

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	GSK2881078 1.0 mg- Female Participants
Arm/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.
Measure Participants	18
Day 14,n=1	1.0000 (NA)
Day 90,n=18	-0.1111 (0.60768)

11. Primary Outcome

Title	Change From Baseline in Urinalysis Parameter; pH: Male Participants
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.
Time Frame	Baseline (Day 1, Pre-dose), Days 28 and 90

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/Group Description	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	19	20
Day 28,n=1,1	1.0000 (NA)	0.5000 (NA)
Day 90,n=19,20	-0.1579 (0.72749)	0.3000 (0.71451)

12. Primary Outcome

Title	Number of Participants With Urinalysis Dipstick Results Post-Baseline Relative to Baseline
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.
Time Frame	Baseline (Day 1, Pre-dose) and up to Day 132

Outcome Measure Data

Analysis Population Description

Safety Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	23	21	23	24
Glucose: increase to trace	0 0%	0 0%	1 4.2%	0 0%
Glucose: increase to 1+	0 0%	0 0%	0 0%	0 0%
Glucose: increase to 2+	0 0%	0 0%	0 0%	0 0%
Glucose: increase to 3+	0 0%	0 0%	0 0%	1 4%
OB: increase to trace	1 4.3%	0 0%	1 4.2%	1 4%
OB: increase to 1+	1 4.3%	1 4.2%	1 4.2%	0 0%
OB: increase to 2+	1 4.3%	2 8.3%	0 0%	0 0%
OB: increase to 3+	0 0%	0 0%	0 0%	1 4%
Protein: increase to trace	2 8.7%	2 8.3%	3 12.5%	6 24%
Protein: increase to 1+	0 0%	3 12.5%	1 4.2%	3 12%
Protein: increase to 2+	0 0%	1 4.2%	0 0%	1 4%
Protein: increase to 3+	0 0%	0 0%	0 0%	0 0%

13. Primary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events
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.
Time Frame	Up to Day 132

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	23	24	24	25
Non-SAEs	15 65.2%	18 75%	13 54.2%	17 68%
SAEs	1 4.3%	2 8.3%	2 8.3%	0 0%

14. Primary Outcome

Title	Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 28
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 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.
Time Frame	Baseline (Day 1, Pre-dose), Day 28

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	20	22	23
Mean (Standard Error) [Percentage change]	4.82 (2.406)	9.34 (2.459)	1.55 (2.940)	9.35 (2.848)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.53
	Confidence Interval	(2-Sided) 90%; -1.30 to 10.36
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	7.80
	Confidence Interval	(2-Sided) 90%; 0.83 to 14.76
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

15. Primary Outcome

Title	Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 56
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 56

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	20	18	21	21
Mean (Standard Error) [Percentage change]	0.08 (2.787)	16.78 (2.925)	5.73 (3.921)	11.07 (3.922)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	16.71
	Confidence Interval	(2-Sided) 90%; 9.86 to 23.56
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	5.35
	Confidence Interval	(2-Sided) 90%; -4.09 to 14.78
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

16. Primary Outcome

Title	Percentage Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 90
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	19	18	18	20
Mean (Standard Error) [Percentage change]	12.76 (4.061)	17.93 (4.179)	7.15 (2.759)	14.17 (2.632)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	5.17
	Confidence Interval	(2-Sided) 90%; -4.67 to 15.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	7.02
	Confidence Interval	(2-Sided) 90%; 0.46 to 13.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

17. Primary Outcome

Title	Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 28
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 28

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	20	22	23
Mean (Standard Error) [Kilograms]	4.2 (3.01)	10.0 (3.08)	3.0 (5.06)	16.5 (4.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	5.9
	Confidence Interval	(2-Sided) 90%; -1.4 to 13.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	13.5
	Confidence Interval	(2-Sided) 90%; 1.6 to 25.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

18. Primary Outcome

Title	Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 56
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 56

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	20	18	21	21
Mean (Standard Error) [Kilograms]	0.6 (4.29)	21.3 (4.50)	8.3 (7.69)	15.7 (7.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	20.7
	Confidence Interval	(2-Sided) 90%; 10.1 to 31.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	7.3
	Confidence Interval	(2-Sided) 90%; -11.1 to 25.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

19. Primary Outcome

Title	Change From Baseline in Maximum Leg Press Strength Following 1 Repetition Maximum (1-RM) at Day 90
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	19	18	18	20
Mean (Standard Error) [Kilograms]	12.3 (4.31)	20.3 (4.45)	14.2 (5.17)	26.0 (4.91)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	8.0
	Confidence Interval	(2-Sided) 90%; -2.5 to 18.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	11.8
	Confidence Interval	(2-Sided) 90%; -0.5 to 24.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

20. Secondary Outcome

Title	Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 28
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 28

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	19	20	22
Mean (Standard Error) [Kilograms]	-0.240 (0.0974)	0.642 (0.1023)	0.055 (0.1920)	0.346 (0.1831)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.882
	Confidence Interval	(2-Sided) 90%; 0.643 to 1.121
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.291
	Confidence Interval	(2-Sided) 90%; -0.156 to 0.738
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

21. Secondary Outcome

Title	Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 56
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 56

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	17	17	18
Mean (Standard Error) [Kilograms]	-0.134 (0.1410)	0.848 (0.1540)	-0.464 (0.1887)	0.663 (0.1829)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.982
	Confidence Interval	(2-Sided) 90%; 0.629 to 1.334
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.127
	Confidence Interval	(2-Sided) 90%; 0.682 to 1.571
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

22. Secondary Outcome

Title	Change From Baseline in Appendicular Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 90
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	17	15	18
Mean (Standard Error) [Kilograms]	-0.434 (0.1657)	0.946 (0.1818)	-0.225 (0.2306)	0.899 (0.2117)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.380
	Confidence Interval	(2-Sided) 90%; 0.964 to 1.795
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.124
	Confidence Interval	(2-Sided) 90%; 0.594 to 1.654
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

23. Secondary Outcome

Title	Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 28
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 28

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	19	20	22
Mean (Standard Error) [Kilograms]	-0.017 (0.2004)	1.150 (0.2106)	0.075 (0.3004)	0.998 (0.2869)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.167
	Confidence Interval	(2-Sided) 90%; 0.677 to 1.658
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.923
	Confidence Interval	(2-Sided) 90%; 0.222 to 1.623
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

24. Secondary Outcome

Title	Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 56
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 56

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	17	17	18
Mean (Standard Error) [Kilograms]	-0.564 (0.2372)	1.522 (0.2587)	-0.373 (0.3820)	1.327 (0.3700)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.085
	Confidence Interval	(2-Sided) 90%; 1.493 to 2.678
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.700
	Confidence Interval	(2-Sided) 90%; 0.801 to 2.600
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

25. Secondary Outcome

Title	Change From Baseline in Total Lean Mass as Assessed by Dual-energy X-ray Absorptiometry (DXA) at Day 90
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	17	15	18
Mean (Standard Error) [Kilograms]	-0.531 (0.3349)	1.577 (0.3666)	-0.424 (0.5056)	1.689 (0.4666)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.108
	Confidence Interval	(2-Sided) 90%; 1.271 to 2.945
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.113
	Confidence Interval	(2-Sided) 90%; 0.949 to 3.277
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

26. Secondary Outcome

Title	Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 28
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 28

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	20	22	23
Mean (Standard Error) [Scores on a scale]	0.3 (0.25)	0.4 (0.26)	0.2 (0.19)	0.3 (0.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 90%; -0.6 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 90%; -0.4 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

27. Secondary Outcome

Title	Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 56
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 56

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	19	21	21
Mean (Standard Error) [Scores on a scale]	0.4 (0.24)	0.4 (0.25)	0.1 (0.24)	0.4 (0.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 90%; -0.6 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 90%; -0.2 to 0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

28. Secondary Outcome

Title	Change From Baseline in Total Short Physical Performance Battery (SPPB) Score at Day 90
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	18	18	20
Mean (Standard Error) [Scores on a scale]	0.3 (0.26)	0.5 (0.28)	0.4 (0.23)	0.5 (0.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 90%; -0.4 to 0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 90%; -0.5 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

29. Secondary Outcome

Title	Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 28
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 28

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	20	22	23
Mean (Standard Error) [Seconds]	-0.644 (0.6333)	-1.196 (0.6491)	-0.464 (0.3841)	-0.537 (0.3763)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.553
	Confidence Interval	(2-Sided) 90%; -2.082 to 0.977
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.073
	Confidence Interval	(2-Sided) 90%; -0.977 to 0.832
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

30. Secondary Outcome

Title	Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 56
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 56

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	19	21	21
Mean (Standard Error) [Seconds]	-1.207 (0.5912)	-2.023 (0.6124)	-0.323 (0.5294)	-0.160 (0.5282)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.816
	Confidence Interval	(2-Sided) 90%; -2.252 to 0.619
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.163
	Confidence Interval	(2-Sided) 90%; -1.096 to 1.422
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

31. Secondary Outcome

Title	Change From Baseline in 'Time for Chair Rise' as Assessed by SPPB at Day 90
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	18	18	20
Mean (Standard Error) [Seconds]	-1.070 (0.6956)	-2.030 (0.7362)	1.144 (1.4013)	-0.793 (1.3401)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.960
	Confidence Interval	(2-Sided) 90%; -2.668 to 0.748
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.937
	Confidence Interval	(2-Sided) 90%; -5.208 to 1.333
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

32. Secondary Outcome

Title	Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 28
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 28

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	20	22	23
Mean (Standard Error) [Seconds]	-0.236 (0.1132)	-0.277 (0.1161)	-0.167 (0.1133)	-0.110 (0.1108)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.040
	Confidence Interval	(2-Sided) 90%; -0.314 to 0.233
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.058
	Confidence Interval	(2-Sided) 90%; -0.209 to 0.324
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

33. Secondary Outcome

Title	Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 56
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 56

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	19	21	21
Mean (Standard Error) [Seconds]	0.010 (0.1487)	-0.276 (0.1560)	-0.093 (0.1437)	-0.284 (0.1438)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.287
	Confidence Interval	(2-Sided) 90%; -0.650 to 0.077
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.191
	Confidence Interval	(2-Sided) 90%; -0.534 to 0.152
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

34. Secondary Outcome

Title	Change From Baseline in 'Time for Fastest Walk for 4 Meter' as Assessed by SPPB at Day 90
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	18	18	20
Mean (Standard Error) [Seconds]	-0.043 (0.2194)	-0.055 (0.2361)	-0.130 (0.1331)	-0.360 (0.1275)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.012
	Confidence Interval	(2-Sided) 90%; -0.555 to 0.532
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.231
	Confidence Interval	(2-Sided) 90%; -0.541 to 0.080
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

35. Secondary Outcome

Title	Change From Baseline in Constant Work Rate (CWR) Duration From Endurance Shuttle Walking Test
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	19	16	18	20
Least Squares Mean (Standard Error) [Seconds]	-6.5 (26.78)	4.6 (29.25)	105.1 (54.94)	-44.2 (51.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	11.1
	Confidence Interval	(2-Sided) 90%; -57.1 to 79.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis was performed by ANCOVA model with Baseline CWR duration as the covariate adjusting for the treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-149.3
	Confidence Interval	(2-Sided) 90%; -280.6 to -18.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis was performed by ANCOVA model with Baseline CWR duration as the covariate adjusting for the treatment.

36. Secondary Outcome

Title	Change From Baseline in Peak Performance From Incremental Shuttle Walking Test
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.
Time Frame	Baseline (Highest non-missing pre-dose assessment from Day-9 and Day 1), Day 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	19	18	18	20
Least Squares Mean (Standard Error) [Meters]	-10.5 (14.76)	-17.2 (15.16)	-7.5 (15.84)	-42.3 (15.02)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-6.7
	Confidence Interval	(2-Sided) 90%; -42.7 to 29.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis was performed by ANCOVA model with Baseline peak performance as the covariate adjusting for the treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-34.8
	Confidence Interval	(2-Sided) 90%; -72.0 to 2.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis was performed by ANCOVA model with Baseline peak performance as the covariate adjusting for the treatment.

37. Secondary Outcome

Title	Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Score at Day 56
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 56

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	19	21	21
Mean (Standard Error) [Scores on a Scale]	-0.8 (0.92)	-1.2 (0.97)	-0.4 (1.14)	-1.0 (1.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 90%; -2.6 to 1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 90%; -3.4 to 2.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

38. Secondary Outcome

Title	Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) Score at Day 90
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	18	18	20
Mean (Standard Error) [Scores on a Scale]	-1.3 (0.79)	-2.2 (0.85)	-1.4 (0.94)	0.8 (0.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 90%; -2.9 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.2
	Confidence Interval	(2-Sided) 90%; 0.0 to 4.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

39. Secondary Outcome

Title	Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Difficulty Score at Day 56
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 for averaged weekly difficulty score.
Time Frame	Baseline (Day -9), Day 56

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	17	12	12	13
Mean (Standard Error) [Scores on a Scale]	3.7 (1.59)	-1.1 (1.80)	1.3 (2.16)	-0.8 (2.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.7
	Confidence Interval	(2-Sided) 90%; -8.9 to -0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 90%; -7.2 to 3.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

40. Secondary Outcome

Title	Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Difficulty Score at Day 90
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 for averaged weekly difficulty score.
Time Frame	Baseline (Day -9), Day 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	15	17	13	11
Mean (Standard Error) [Scores on a Scale]	2.0 (1.90)	-2.9 (1.84)	2.8 (2.56)	-1.2 (2.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.9
	Confidence Interval	(2-Sided) 90%; -9.5 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.1
	Confidence Interval	(2-Sided) 90%; -10.3 to 2.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

41. Secondary Outcome

Title	Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Amount Score at Day 56
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 for averaged weekly amount score.
Time Frame	Baseline (Day -9), Day 56

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	17	12	12	13
Mean (Standard Error) [Scores on a Scale]	3.3 (1.09)	0.2 (1.24)	2.5 (1.83)	2.3 (1.77)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.1
	Confidence Interval	(2-Sided) 90%; -5.9 to -0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 90%; -4.6 to 4.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

42. Secondary Outcome

Title	Change From Baseline in Participant Reported Outcome (PRO)Active Individual Component: Amount Score at Day 90
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 for averaged weekly amount score.
Time Frame	Baseline (Day -9), Day 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	15	17	13	11
Mean (Standard Error) [Scores on a Scale]	-0.2 (2.05)	3.8 (1.98)	-0.8 (2.33)	2.7 (2.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	4.0
	Confidence Interval	(2-Sided) 90%; -0.8 to 8.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	3.5
	Confidence Interval	(2-Sided) 90%; -2.3 to 9.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

43. Secondary Outcome

Title	Change From Baseline in Participant Reported Outcome (PRO)Active Total Score at Day 56
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 scale for each domain. The 'total score' was obtained by calculating the average between two domains. Total score has the range 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. Adjusted means and SE are presented
Time Frame	Baseline (Day -9), Day 56

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	17	12	12	13
Mean (Standard Error) [Scores on a Scale]	3.7 (0.89)	-0.5 (1.03)	2.1 (1.09)	0.5 (1.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-4.2
	Confidence Interval	(2-Sided) 90%; -6.5 to -1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 90%; -4.1 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

44. Secondary Outcome

Title	Change From Baseline in Participant Reported Outcome (PRO)Active Total Score at Day 90
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 scale for each domain. The 'total score' was obtained by calculating the average between two domains. Total score has the range 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. Adjusted means and SE are presented.
Time Frame	Baseline (Day -9), Day 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	15	17	13	11
Mean (Standard Error) [Scores on a Scale]	1.3 (1.20)	0.3 (1.14)	1.2 (1.57)	0.5 (1.66)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 90%; -3.8 to 1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 90%; -4.6 to 3.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	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.

45. Secondary Outcome

Title	Change From Baseline in Steps Per Day (Physical Activity Measure) as Assessed Via an Accelerometer
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.
Time Frame	Baseline (Day -9), Days 56 and 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	17	17	14	17
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)

46. Secondary Outcome

Title	Change From Baseline in Vector Magnitude Unit Per Wear Time (Physical Activity Measure) as Assessed Via an Accelerometer
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.
Time Frame	Baseline (Day -9), Days 56 and 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	17	17	14	17
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)

47. Secondary Outcome

Title	Number of Participants With Participant Global Impression of Change (PGIC) Score Over Time
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.
Time Frame	Days 14, 28, 56 and 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	20	23	23
Day 14, much worse,n=21,20,23,23	0 0%	0 0%	0 0%	0 0%
Day 14, worse,n=21,20,23,23	0 0%	0 0%	0 0%	1 4%
Day 14, slightly worse,n=21,20,23,23	0 0%	1 4.2%	0 0%	0 0%
Day 14, no change,n=21,20,23,23	6 26.1%	5 20.8%	9 37.5%	9 36%
Day 14, slightly better,n=21,20,23,23	7 30.4%	7 29.2%	4 16.7%	4 16%
Day 14, better,n=21,20,23,23	7 30.4%	5 20.8%	8 33.3%	7 28%
Day 14, much better,n=21,20,23,23	1 4.3%	2 8.3%	2 8.3%	2 8%
Day 28, much worse,n=21,20,21,22	0 0%	0 0%	0 0%	0 0%
Day 28, worse,n=21,20,21,22	0 0%	0 0%	0 0%	0 0%
Day 28, slightly worse,n=21,20,21,22	1 4.3%	2 8.3%	0 0%	0 0%
Day 28, no change,n=21,20,21,22	3 13%	6 25%	4 16.7%	6 24%
Day 28, slightly better,n=21,20,21,22	9 39.1%	6 25%	10 41.7%	7 28%
Day 28, better,n=21,20,21,22	5 21.7%	6 25%	5 20.8%	7 28%
Day 28, much better,n=21,20,21,22	3 13%	0 0%	2 8.3%	2 8%
Day 56, much worse,n=21,19,21,21	0 0%	0 0%	0 0%	0 0%
Day 56, worse,n=21,19,21,21	0 0%	0 0%	0 0%	0 0%
Day 56, slightly worse,n=21,19,21,21	1 4.3%	3 12.5%	1 4.2%	4 16%
Day 56, no change,n=21,19,21,21	2 8.7%	5 20.8%	4 16.7%	5 20%
Day 56, slightly better,n=21,19,21,21	6 26.1%	4 16.7%	7 29.2%	5 20%
Day 56, better,n=21,19,21,21	10 43.5%	6 25%	8 33.3%	5 20%
Day 56, much better,n=21,19,21,21	2 8.7%	1 4.2%	1 4.2%	2 8%
Day 90, much worse,n=21,18,18,20	0 0%	0 0%	0 0%	0 0%
Day 90, worse,n=21,18,18,20	0 0%	1 4.2%	0 0%	0 0%
Day 90, slightly worse,n=21,18,18,20	1 4.3%	0 0%	0 0%	0 0%
Day 90, no change,n=21,18,18,20	9 39.1%	8 33.3%	5 20.8%	6 24%
Day 90, slightly better,n=21,18,18,20	7 30.4%	3 12.5%	9 37.5%	9 36%
Day 90, better,n=21,18,18,20	3 13%	4 16.7%	4 16.7%	4 16%
Day 90, much better,n=21,18,18,20	1 4.3%	2 8.3%	0 0%	1 4%

48. Secondary Outcome

Title	Number of Participants With Participant Global Rating of Severity (PGRS) Score Over Time
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.
Time Frame	Days 1 and 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	20	23	23
Day 1, mild,n=21,20,23,23	2 8.7%	0 0%	0 0%	2 8%
Day 1, moderate,n=21,20,23,23	9 39.1%	13 54.2%	11 45.8%	12 48%
Day 1, severe,n=21,20,23,23	8 34.8%	7 29.2%	12 50%	8 32%
Day 1, very severe,n=21,20,23,23	2 8.7%	0 0%	0 0%	1 4%
Day 90, mild,n=21,18,18,20	4 17.4%	4 16.7%	1 4.2%	5 20%
Day 90, moderate,n=21,18,18,20	9 39.1%	7 29.2%	9 37.5%	2 8%
Day 90, severe,n=21,18,18,20	6 26.1%	6 25%	8 33.3%	12 48%
Day 90, very severe,n=21,18,18,20	2 8.7%	1 4.2%	0 0%	1 4%

49. Secondary Outcome

Title	Change From Baseline in St. George Respiratory Questionnaire (SGRQ) for COPD (SGRQ-c) Total Score
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	17	18	20
Least Squares Mean (Standard Error) [Scores on a scale]	-3.9 (1.71)	-0.9 (1.90)	-1.7 (1.87)	0.4 (1.77)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	3.0
	Confidence Interval	(2-Sided) 90%; -1.4 to 7.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis was performed by ANCOVA model with Baseline total score as the covariate adjusting for the treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	2.1
	Confidence Interval	(2-Sided) 90%; -2.3 to 6.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis was performed by ANCOVA model with Baseline total score as the covariate adjusting for the treatment.

50. Secondary Outcome

Title	Change From Baseline in SGRQ-c Symptoms Score
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	17	18	20
Least Squares Mean (Standard Error) [Scores on a scale]	-4.0 (2.95)	-1.4 (3.29)	-3.5 (3.38)	-4.0 (3.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	2.6
	Confidence Interval	(2-Sided) 90%; -5.0 to 10.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis was performed by ANCOVA model with Baseline symptoms score as the covariate adjusting for the treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 90%; -8.4 to 7.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis was performed by ANCOVA model with Baseline symptoms score as the covariate adjusting for the treatment.

51. Secondary Outcome

Title	Change From Baseline in SGRQ-c Activity Score
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	17	18	20
Least Squares Mean (Standard Error) [Scores on a scale]	-5.4 (2.00)	-3.4 (2.23)	1.2 (2.57)	1.6 (2.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 90%; -3.2 to 7.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis was performed by ANCOVA model with Baseline activity score as the covariate adjusting for the treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 90%; -5.6 to 6.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis was performed by ANCOVA model with Baseline activity score as the covariate adjusting for the treatment.

52. Secondary Outcome

Title	Change From Baseline in SGRQ-c Impact Score
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.
Time Frame	Baseline (Day 1, Pre-dose), Day 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed.

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	17	18	20
Least Squares Mean (Standard Error) [Scores on a scale]	-2.8 (2.03)	0.6 (2.25)	-2.7 (1.76)	0.8 (1.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo- Female Participants, GSK2881078 1.0 mg- Female Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	3.4
	Confidence Interval	(2-Sided) 90%; -1.7 to 8.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis was performed by ANCOVA model with Baseline impact score as the covariate adjusting for the treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo- Male Participants, GSK2881078 2.0 mg- Male Participants
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Square Means
	Estimated Value	3.5
	Confidence Interval	(2-Sided) 90%; -0.7 to 7.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Analysis was performed by ANCOVA model with Baseline impact score as the covariate adjusting for the treatment.

53. Secondary Outcome

Title	Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
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.
Time Frame	Baseline (Day 1, Pre-dose), Days 56 and 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	19	21	21
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)

54. Secondary Outcome

Title	Change From Baseline in Sniff Nasal Inspiratory Pressure (SnIP)
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.
Time Frame	Baseline (Day 1, Pre-dose), Days 56 and 90

Outcome Measure Data

Analysis Population Description

Analysis Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Arm/Group Title	Placebo- Female Participants	GSK2881078 1.0 mg- Female Participants	Placebo- Male Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.	Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.	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.
Measure Participants	21	19	21	21
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)

55. Secondary Outcome

Title	Clearance (CL) of GSK2881078 Following Oral Dose in Participants
Description	Blood samples were collected at designated timepoints. Pharmacokinetics (PK) parameters of GSK2881078 were calculated using non-compartmental methods.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	GSK2881078 1.0 mg- Female Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.
Measure Participants	21	24
Geometric Mean (Geometric Coefficient of Variation) [Liters per hour]	0.393 (59.5)	0.476 (44.0)

56. Secondary Outcome

Title	Volume of Distribution at Steady State (Vss) of GSK2881078 Following Oral Dose in Participants
Description	Blood samples were collected at designated timepoints. PK parameters of GSK2881078 were calculated using non-compartmental methods.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic Population

Arm/Group Title	GSK2881078 1.0 mg- Female Participants	GSK2881078 2.0 mg- Male Participants
Arm/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.	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.
Measure Participants	21	24
Geometric Mean (Geometric Coefficient of Variation) [Liters]	39.4 (16.3)	48.3 (29.8)

Adverse Events

Time Frame	Serious adverse events (SAEs) and non-serious AEs were collected from the start of study treatment until up to Day 132
Adverse Event Reporting 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.
Arm/Group Title	Placebo- Female Participants		GSK2881078 1.0 mg- Female Participants		Placebo- Male Participants		GSK2881078 2.0 mg- Male Participants
Arm/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.		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.		Male participants, 50 to 75 years of age, were administered orally two capsules of GSK2881078 matching placebo once daily over 13 weeks.		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.
All Cause Mortality
	Placebo- Female Participants		GSK2881078 1.0 mg- Female Participants		Placebo- Male Participants		GSK2881078 2.0 mg- Male Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/24 (0%)		0/24 (0%)		0/25 (0%)
Serious Adverse Events
	Placebo- Female Participants		GSK2881078 1.0 mg- Female Participants		Placebo- Male Participants		GSK2881078 2.0 mg- Male Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/23 (4.3%)		2/24 (8.3%)		2/24 (8.3%)		0/25 (0%)
Cardiac disorders
Myocardial infarction	0/23 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/25 (0%)	0
Hepatobiliary disorders
Cholecystitis acute	0/23 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	0/25 (0%)	0
Infections and infestations
Diverticulitis	0/23 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/25 (0%)	0
Infective exacerbation of chronic obstructive airways disease	1/23 (4.3%)	1	0/24 (0%)	0	0/24 (0%)	0	0/25 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	0/23 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	0/25 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo- Female Participants		GSK2881078 1.0 mg- Female Participants		Placebo- Male Participants		GSK2881078 2.0 mg- Male Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/23 (65.2%)		18/24 (75%)		13/24 (54.2%)		17/25 (68%)
Gastrointestinal disorders
Diarrhoea	1/23 (4.3%)	1	0/24 (0%)	0	1/24 (4.2%)	1	1/25 (4%)	1
Abdominal pain upper	0/23 (0%)	0	1/24 (4.2%)	1	1/24 (4.2%)	1	0/25 (0%)	0
Constipation	0/23 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	1/25 (4%)	1
Nausea	1/23 (4.3%)	1	1/24 (4.2%)	1	0/24 (0%)	0	0/25 (0%)	0
General disorders
Chest pain	0/23 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	1/25 (4%)	1
Fatigue	1/23 (4.3%)	1	0/24 (0%)	0	0/24 (0%)	0	1/25 (4%)	1
Non-cardiac chest pain	1/23 (4.3%)	1	0/24 (0%)	0	1/24 (4.2%)	1	0/25 (0%)	0
Infections and infestations
Nasopharyngitis	5/23 (21.7%)	5	2/24 (8.3%)	3	1/24 (4.2%)	1	1/25 (4%)	2
Urinary tract infection	1/23 (4.3%)	1	1/24 (4.2%)	1	0/24 (0%)	0	1/25 (4%)	2
Sinusitis	0/23 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	1/25 (4%)	1
Injury, poisoning and procedural complications
Contusion	3/23 (13%)	3	1/24 (4.2%)	1	0/24 (0%)	0	0/25 (0%)	0
Muscle strain	0/23 (0%)	0	1/24 (4.2%)	1	1/24 (4.2%)	1	0/25 (0%)	0
Investigations
Alanine aminotransferase increased	0/23 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	2/25 (8%)	2
Aspartate aminotransferase increased	0/23 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	1/25 (4%)	1
Blood 25-hydroxycholecalciferol decreased	0/23 (0%)	0	2/24 (8.3%)	2	0/24 (0%)	0	0/25 (0%)	0
Low density lipoprotein increased	0/23 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	1/25 (4%)	1
Metabolism and nutrition disorders
Decreased appetite	0/23 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	1/25 (4%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	0/23 (0%)	0	3/24 (12.5%)	5	2/24 (8.3%)	2	2/25 (8%)	2
Muscle spasms	1/23 (4.3%)	1	2/24 (8.3%)	2	0/24 (0%)	0	3/25 (12%)	3
Back pain	0/23 (0%)	0	3/24 (12.5%)	3	0/24 (0%)	0	2/25 (8%)	3
Musculoskeletal chest pain	0/23 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	2/25 (8%)	2
Musculoskeletal Pain	1/23 (4.3%)	1	1/24 (4.2%)	1	0/24 (0%)	0	1/25 (4%)	1
Neck pain	1/23 (4.3%)	1	0/24 (0%)	0	1/24 (4.2%)	1	0/25 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adrenal adenoma	0/23 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	1/25 (4%)	1
Nervous system disorders
Headache	0/23 (0%)	0	2/24 (8.3%)	2	0/24 (0%)	0	2/25 (8%)	2
Renal and urinary disorders
Haematuria	0/23 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	1/25 (4%)	1
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	6/23 (26.1%)	6	7/24 (29.2%)	8	2/24 (8.3%)	2	3/25 (12%)	4
Epistaxis	0/23 (0%)	0	0/24 (0%)	0	2/24 (8.3%)	2	1/25 (4%)	1
Dyspnoea	1/23 (4.3%)	1	0/24 (0%)	0	1/24 (4.2%)	1	0/25 (0%)	0
Pulmonary mass	0/23 (0%)	0	0/24 (0%)	0	1/24 (4.2%)	1	1/25 (4%)	1
Skin and subcutaneous tissue disorders
Dry skin	1/23 (4.3%)	1	1/24 (4.2%)	1	0/24 (0%)	0	1/25 (4%)	1
Pruritus	0/23 (0%)	0	1/24 (4.2%)	1	0/24 (0%)	0	1/25 (4%)	1
Vascular disorders
Hypertension	0/23 (0%)	0	1/24 (4.2%)	1	2/24 (8.3%)	2	0/25 (0%)	0
Haematoma	1/23 (4.3%)	1	1/24 (4.2%)	1	0/24 (0%)	0	0/25 (0%)	0
Hypotension	0/23 (0%)	0	0/24 (0%)	0	2/24 (8.3%)	2	0/25 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.