| Eligibility |
Inclusion Criteria:
- Subject has a body mass index of 18.5 to 35.0 kg/m2, inclusive.
- Subject has a score of greater than 4 and less than or equal to 10 on a Short physical
performance battery (SPPB).
- Subject is able to complete the 6-minute walk test at screening without an assistive
device or the help of another person.
- Subject is able to successfully complete the prestudy isokinetic knee extension (120
contractions). These assessments may be repeated once at the investigator's discretion
(within the screening window).
- Subject is able to communicate well with the investigator and to understand and comply
with the requirements of the study.
- Subject has a mini-mental state examination (MMSE) score of greater than 21 at
screening.
- Subject is currently not following a a strenuous weekly exercise regimen.
- A sexually active male subject with female partner(s) of childbearing potential is
eligible if:
- Male subject agrees to use a male condom starting at screening and continue
throughout study treatment and for 90 days after the final study drug
administration.
- If the male subject has not had a vasectomy or is not sterile as defined below,
the male subject's female partner(s) is utilizing 1 form of highly effective
birth control starting at screening and continuing throughout study treatment and
for 90 days after the male subject receives final study drug administration.
- Male subject must not donate sperm starting at screening and throughout the study
period, and for 90 days after the final study drug administration.
- Male subject with a pregnant or breastfeeding partner(s) must agree to remain
abstinent or use a condom for the duration of the pregnancy or time partner is
breastfeeding throughout the study period and for 90 days after the final study drug
administration.
- Subject agrees not to participate in another interventional study while participating
in the present study, defined as from signing the informed consent form for the
current study until completion of the Follow-up visit for this study.
Exclusion Criteria:
- Subject has had previous exposure to CK-2127107.
- Subject has any of the liver function tests (aspartate aminotransferase, alanine
aminotransferase, alkaline phosphatase, ?-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.
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