Dilated Cardiomyopathy
Conditions
Brief summary
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
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.
Interventions
DRUGMYK-491 or placebo
Oral suspension
Sponsors
MyoKardia, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Subjects will be randomized 6:2 to MYK-491:placebo within each cohort.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Other
| Measure | Time frame |
|---|---|
| Relationship between MYK-491 plasma concentration and QTc interval | 7 days |
| The change from baseline in LVFS, LVEF, LVSV and SET by TTE | 7 days |
| SET while using photoplethysmography | 7 days |
| Relationship between MYK-491 plasma concentrations/PK parameters and PD parameters | 7 days |
| Plasma concentrations of metabolites of MYK-491 in plasma and urine | 7 days |
Countries
Australia
Outcome results
None listed