A Single Ascending Dose Study Assessing the Safety, Tolerability, PK and PD of MYK-491

Randomized, Placebo-Controlled Study of Safety, Tolerability, Preliminary Pharmacokinetics and Pharmacodynamics of Single Ascending Oral Doses of MYK-491 in Healthy Adult Volunteers

Up to 72 healthy volunteers will be given a single dose of MYK-491 or placebo and be monitored for safety and tolerability over a 7 day period.

Up to 72 healthy volunteers will be given a single dose of MYK-491 or placebo and be monitored for safety and tolerability over a 7 day period. After the 28 day screening period, the eligible subject will be admitted to the clinical site and will receive a single dose of study drug or placebo. Subjects will be confined to the clinical site for five days (Day -1 to Day 4) and will return to the clinic on Day 7 for a safety follow-up.

Inclusion Criteria:

• Weight between 60 and 90 kg inclusive
• Resting heart rate of < 80 beats per minute
• Documented LVEF greater than or equal to 55% during Screening
• Normal electrocardiogram (ECG) at Screening
• Normal acoustic windows on transthoracic echocardiograms at Screening
• All safety laboratory parameters within normal limits at Screening
• History or evidence of another clinically significant disorder, in the opinion of the investigator.

Exclusion Criteria:

• Active infection
• History of coronary artery disease
• History of malignancy with the exception of in situ cervical cancer more than 5 years prior to Screening or surgically-excised non-melanomatous skin cancers more than 2 years prior to Screening
• Positive serology tests at screening
• Current use of tobacco or nicotine-containing products exceeding 10 per day.