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Completed

NCT Number: NCT03359473

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

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.

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Key information

Conditions

Cachexia Body Weight Body Weight Changes Chronic Disease Disease Attributes Lung Diseases Lung Diseases, Obstructive Muscle Weakness Muscular Diseases Musculoskeletal Diseases Nervous System Diseases Neurologic Manifestations Neuromuscular Manifestations Pathologic Processes Pathological Conditions, Signs and Symptoms Pulmonary Disease, Chronic Obstructive Respiratory Tract Diseases Signs and Symptoms Thinness Weight Loss

Age range

50 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

GSK Investigational Site, Frankfurt am Main, Hesse, Germany

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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. b) 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.

Treatment and study plan

GSK2881078

Drug

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.

Matching Placebo

Drug

Subjects will be administered two capsules of GSK2881078 matching placebo once daily by the oral route.

Primary outcomes

  1. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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 outcomes

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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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)

    Time frame: 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)

    Time frame: 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

    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)

    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

    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)

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

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Collaborators

  • Parexel

Registry information

Official study 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

Important dates

Study start
2018
Primary completion
2019
Study completion
2019
First posted
Dec 2, 2017
Registry last updated
Jul 15, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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