A Study to Assess the Effect of CK-2127107 on Physical Function in Subjects With Chronic Obstructive Pulmonary Disease

Enrolled participants will be randomly assigned to 1 of 2 treatment sequences and will
receive both CK-2127107 and matching placebo over 2 treatment periods.

Inclusion Criteria:

- Subject has a body mass index (BMI) of 18-35 kg/m2 inclusive.

- Subject must have all of the following:

- Clinical diagnosis of moderate to severe COPD, with a postbronchodilator FEV1/FVC
ratio < 70% and 30% ≤ FEV1 < 65% predicted at screening. The predicted values for
normal spirometry will be those recommended by the American Thoracic Society
(ATS) / European Respiratory Society (ERS) [Miller et al, 2005].

- General stable health with no change in medication (including non-COPD agents and
dietary aids/food supplements) within 2 weeks prior to screening, no systemic
corticosteroid administration (topical or inhaled corticosteroids are allowed)
within 6 weeks prior to screening, no exacerbations or hospitalization within 6
weeks prior to screening.

- Current or ex-smokers with a smoking history of at least 10 pack years.

- Grade of 2 or 3 on the Modified Medical Research Council (mMRC) Dyspnea Scale at
screening:

1. Grade 2: walks slower than people of the same age on the level because of
breathlessness or has to stop for breath when walking at own pace on the
level.

2. Grade 3: stops for breath after walking about 100 meters or after a few
minutes on the level.

- Subject is able to complete technically acceptable respiratory muscle strength tests,
spirometry, physical performance test and exercise tests.

- Female subject must either:

- Be of non-child bearing potential: Postmenopausal (defined as at least 1 year
without any menses) prior to screening, or documented surgically sterile.

- Or, if of childbearing potential: Agree not to try to become pregnant during the
study and for 28 days after the last dose, and have a negative serum pregnancy
test at screening, and, if heterosexually active, agree to consistently use 2
forms of highly-effective birth control (at least 1 of which must be a barrier
method) starting at screening, throughout the study, and for 28 days after the
last dose.

- Female subject must agree not to breastfeed starting at screening and throughout the
study and for 28 days after the last dose.

- Female subject must not donate ova starting at screening, throughout the study and for
28 days after the last dose.

- Male subject and their female spouse/partners who are of childbearing potential must
be using highly effective form of contraception consisting of 2 forms of birth control
(at least 1 of which must be a barrier method) starting at screening, and continuing
throughout the study and for 90 days after the last dose.

- Male subject must not donate sperm starting at screening, throughout the study and for
90 days after the last dose.

- Subject agrees not to participate in another interventional study from screening
through the follow-up visit (FUV) of the study.

Exclusion Criteria:

- Subject has previously enrolled in a clinical study of CK-2127107.

- Subject has any clinically significant abnormality following the investigator's review
of the physical examination, ECG and protocol-defined clinical laboratory tests at
screening. A significant abnormality is defined as an abnormality which, in the
opinion of the investigator, may (i) put the subject at risk because of participation
in the study, (ii) influence the results of the study or (iii) cause concern regarding
the subject's ability to participate in the study.

- Subject has any of the liver function tests (LFTs; i.e., aspartate aminotransferase
[AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], γ-glutamyl
transferase [GGT] and/or total bilirubin [TBL]) above 1.5 times the upper limit of
normal (ULN) at screening. These assessments may be repeated once at the
investigator's discretion (within the screening window).

- Subject has an estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2
by the Cockcroft-Gault equation at screening.

- Subject has a serious cardiovascular disease, including a current New York Heart
Association (NYHA) class III or IV congestive heart failure or clinically significant
valvular disease, history of cardiac arrest, uncontrolled angina or arrhythmia,
untreated serious conduction disorder (e.g., third-degree heart block), or acute
myocardial ischemic condition suspected on the ECG at screening (e.g., ST-segment
elevation, ST-segment depressions > 2 mm).

- Subject has had a myocardial infarction or other acute coronary syndrome, major heart
surgery (i.e., valve replacement or bypass surgery), stroke, deep vein thrombosis or
pulmonary embolus in the 6 months prior to screening.

- Subject has known active tuberculosis.

- Subject has undergone thoracotomy with pulmonary resection (except for sub-lobar
resection).

- Subject has resting pulse < 40 bpm or > 100 bpm; resting systolic blood pressure > 160
mm Hg or < 90 mm Hg; resting diastolic blood pressure > 100 mm Hg at screening. These
assessments may be repeated once at the investigator's discretion (within the
screening window).

- Subject desaturates to SpO2 < 85% for at least 1 minute on screening IET.

- Subject has a limitation of exercise performance as a result of factors other than
fatigue or exertional dyspnea/shortness of breath (considered to be due to COPD), such
as arthritis in the leg, angina pectoris, heart failure, claudication or morbid
obesity.

- Subject has a CWR cycle ergometry endurance time less than 4 or greater than 8 minutes
after WR adjustment procedures.

- Subject has used the following drugs within 14 days prior to day -1:

- Strong cytochrome P450 (CYP)3A4 inhibitor (e.g., itraconazole, clarithromycin).

- Strong CYP3A4 inducer (e.g., barbiturates, rifampin).

- Subject has hemoglobin (Hb) concentration below 10.0 g/dL at screening.

- Subject has a cancer requiring treatment currently or in the past 3 years (except
primary nonmelanoma skin cancer, carcinoma in situ or cancers that have an excellent
prognosis such as early stage breast or prostate cancer).

- Subject giving a history of asthma, allergic rhinitis or atopy shall be evaluated by
the investigator to determine whether the subject's predominant diagnosis is COPD
rather than asthma.

- Subject has neurological conditions or neuromuscular diseases that are causing
impaired muscle function or mobility.

- Subject has a current diagnosis of schizophrenia, other psychotic disorders or bipolar
disorder.

- Subject in the active phase of pulmonary rehabilitation or had completed pulmonary
rehabilitation or exercise training within the 13 weeks prior to screening.

- Subject has severe and/or uncontrolled medical conditions that could interfere with
the study (e.g., severe neurological deficit after stroke, developed diabetic
peripheral neuropathy, respiratory diseases requiring daytime supplemental oxygen,
infection, gastrointestinal disorder, uncontrolled pain or any other non-stable
illness) as judged by the medical investigator.

- Subject has a known history of positive test for hepatitis B surface antigen (HBsAg)
or hepatitis C antibody or history of a positive test for human immunodeficiency virus
(HIV) infection.

- Subject has a history of alcoholism or drug/chemical substance abuse within 2 years
prior to screening.

- Subject has used any medications known to affect physical function or muscle mass
including androgen supplements, anti-androgens (such as luteinizing hormone-releasing
hormone [LHRH] agonists), anti-estrogen (tamoxifen, etc.), recombinant human growth
hormone (rhGH), insulin, oral beta adrenergic agonists, megestrol acetate, dronabinol,
metformin or other drugs which, in the opinion of the investigator, might influence
physical function or muscle mass within 6 weeks prior to screening.

- Subject has participated in any interventional clinical study or has been treated with
any investigational drugs within 28 days or 5 half-lives whichever is longer, prior to
the initiation of screening.

- Subject has any other condition that in the opinion of the investigator precludes the
subject's participation in the trial.