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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Dilated Cardiomyopathy

Intervention / Treatment
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* Drug: MYK-491 or placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single oral dose of MYK-491<br>single-dose, oral suspension | Drug: MYK-491 or placebo<br>* Oral suspension<br>|
| Placebo Comparator: Single oral dose of placebo<br>single-dose, oral suspension | Drug: MYK-491 or placebo<br>* Oral suspension<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability assessments will include treatment emergent AEs and SAEs, ECG recordings, vital signs, hs-troponin 1 concentrations, laboratory abnormalities and physical exam abnormalities |  | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma drug concentration (Cmax) |  | 7 days | 
| Maximum observed plasma concentration (Tmax) |  | 7 days | 
| Area under the plasma concentration-time curve (AUC) |  | 7 days | 
| First-order terminal elimination half-life (t1/2) |  | 7 days | 
| Mean retention time (MRT) |  | 7 days |