A Study to Assess the Anti-fatigability Effect of CK-2127107 in Elderly Male and Female Subjects With Limitations in Mobility

Exclusion Criteria

• •Subject has had previous exposure to CK-2127107.
• •Subject has any of the liver function tests (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyl transferase and total bilirubin) above 1.5 times the upper limit of normal at day -1. In such a case, the assessment may be repeated once.
• •Subject has an estimated glomerular filtration rate less than 30 mL/min per 1.73 m2 by the Cockcroft-Gault equation at screening.
• •Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding seasonal allergies) prior to study drug administration.
• •Subject has/had a febrile illness or a symptomatic viral, bacterial (including upper respiratory infections), or fungal (noncutaneous) infection within 1 week prior to day -1.
• •Subject has any condition which makes the subject unsuitable for study participation.
• •Subject has a serious cardiovascular disease, including a current New York Heart Association class II, class III or IV congestive heart failure or clinically significant valvular disease, history of cardiac arrest, uncontrolled angina or arrhythmia, chronic atrial fibrillation regardless of ventricular rate, persistent atrioventricular conduction block \> first degree, or acute myocardial ischemic condition suspected on the Electrocardiogram (ECG) at screening (e.g., ST-segment elevation, down-sloping ST-segment depressions \> 2 mm).
• •Subject has 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 past 6 months prior to screening.
• •Subject has any of the following, with or without blood pressure medication: a pulse \< 40 or \> 100 bpm; mean systolic blood pressure \>160 mmHg; mean diastolic blood pressure \> 100 mmHg (based on the measurements taken in triplicate after subject has been resting in seated position for 5 minutes; pulse will be measured automatically) at day 1. These assessments may be repeated once at the investigator's discretion (within the screening window).
• •Subject has used the following drugs:
• •* Strong cytochrome P450 (CYP) 3A4 inhibitor (e.g., itraconazole, clarithromycin; within 14 days prior to day 1
• •* CYP3A4 inducer (e.g., barbiturates, rifampin) within 14 days prior to day 1.
• •* Any medications known to affect physical function or muscle mass including androgen supplements, anti-androgens (such as luteinizing hormone-releasing hormone \[LHRH\] agonist, anti-estrogen \[tamoxifen, etc\],.), recombinant human growth hormone \[rhGH\] insulin, oral beta adrenergic agonists, megestrol acetate, dronabinol, metformin or other drugs) which might influence physical function or muscle mass within 6 weeks prior to screening.
• •Subject has had significant blood loss, donated 1 unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to screening.
• •Subject has/had hemoglobin concentration below 10.0 g/dL at screening.
• •Subject has/had \> 20% weight loss in the previous 3 months prior to screening.
• •Subject has/had chronic medications introduced within 2 weeks prior to screening.
• •Subject has/had 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 has/had a diagnosed neurological conditions or neuromuscular diseases causing impaired muscle function or mobility.
• •Subject has current diagnosis of schizophrenia, other psychotic disorders or bipolar disorder.
• •Subject has severe and/or uncontrolled medical conditions that could interfere with the study (e.g., severe neurological deficit after stroke, diabetic peripheral neuropathy, respiratory diseases requiring daytime supplemental oxygen, infection, gastrointestinal disorder, uncontrolled pain from osteoarthritis that would limit completion of study procedures or any other nonstable illness).
• •Subject has a positive serology test for hepatitis B surface antigen, hepatitis B core antibody, hepatitis A virus antibodies (immunoglobulin M), hepatitis C virus antibodies, or antibodies to human immunodeficiency virus (HIV) type 1 at screening.
• •Subject has/had a surgical procedure requiring general anesthesia within 2 months prior to screening, or a planned surgical procedure requiring general anesthesia during study period.
• •Subject is using any nonmedical therapy, or dietary aids/food supplements that have not been at a stable dose for at least 4 weeks prior to baseline and/or are anticipated to change dosing regimen during the study.
• •Subject has history of drug/chemical substance or alcohol abuse within 2 years prior to screening.
• •Subject has received investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening.