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

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.