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

NCT ID: NCT03359473

Last Updated: 2020-07-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 97 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-28
• Study Completion Date: 2019-11-19

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.

Conditions

Cachexia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

GSK2881078

Intervention Type: 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.

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.

Group Type: PLACEBO_COMPARATOR

Matching Placebo

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

GSK2881078

Intervention Type: 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.

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.

Group Type: PLACEBO_COMPARATOR

Matching Placebo

Intervention Type: DRUG

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

Interventions

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.

Intervention Type: DRUG

Matching Placebo

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

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Torrance, California, United States

GSK Investigational Site

Jacksonville, Florida, United States

GSK Investigational Site

High Point, North Carolina, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Spartanburg, South Carolina, United States

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Großhansdorf, Schleswig-Holstein, Germany

GSK Investigational Site

Leicester, Leicestershire, United Kingdom

GSK Investigational Site

Harefield, Middlesex, United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

London, Greater London, , United Kingdom

Countries

United States; Germany; United Kingdom

References

Tabberer M, Williamson N, Tatlock S, Gater A, Grimes R, Akinseye C, Neil D, Mahon-Smith A, Nelsen L. Qualitative interviews of patients with COPD and muscle weakness enrolled in a clinical trial evaluating a new anabolic treatment: patient perspectives of disease experience, trial participation and outcome assessments. J Patient Rep Outcomes. 2024 Apr 20;8(1):45. doi: 10.1186/s41687-024-00712-0.

Reference Type: DERIVED

PMID: 38641716 (View on PubMed)

Mohan D, Rossiter H, Watz H, Fogarty C, Evans RA, Man W, Tabberer M, Beerahee M, Kumar S, Millns H, Thomas S, Tal-Singer R, Russell AJ, Holland MC, Akinseye C, Neil D, Polkey MI. Selective androgen receptor modulation for muscle weakness in chronic obstructive pulmonary disease: a randomised control trial. Thorax. 2023 Mar;78(3):258-266. doi: 10.1136/thorax-2021-218360. Epub 2022 Oct 25.

Reference Type: DERIVED

PMID: 36283827 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

2017-001148-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

200182

Identifier Type: -

Identifier Source: org_study_id