Clinical trial NCT03062956: A Single Ascending Dose Study Assessing the Safety, Tolerability, PK and PD of MYK-491
Official title: Randomized, Placebo-Controlled Study of Safety, Tolerability, Preliminary Pharmacokinetics and Pharmacodynamics of Single Ascending Oral Doses of MYK-491 in Healthy Adult Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dilated Cardiomyopathy
Lead sponsor: MyoKardia, Inc.
Sponsor class: INDUSTRY
First posted: 2017-02-24
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 7 days
Secondary outcomes:
measure: Maximum observed plasma drug concentration (Cmax)
timeFrame: 7 days
measure: Maximum observed plasma concentration (Tmax)
timeFrame: 7 days
measure: Area under the plasma concentration-time curve (AUC)
timeFrame: 7 days
measure: First-order terminal elimination half-life (t1/2)
timeFrame: 7 days
measure: Mean retention time (MRT)
timeFrame: 7 days
Other outcomes:
measure: The change from baseline in LVFS, LVEF, LVSV and SET by TTE
timeFrame: 7 days
measure: SET while using photoplethysmography
timeFrame: 7 days
measure: Relationship between MYK-491 plasma concentrations/PK parameters and PD parameters
timeFrame: 7 days
measure: Plasma concentrations of metabolites of MYK-491 in plasma and urine
timeFrame: 7 days
measure: Relationship between MYK-491 plasma concentration and QTc interval
timeFrame: 7 days
Locations:
city: Melbourne
country: Australia
facility: Nucleus Network
state: Victoria
Study officials:
affiliation: Nucleus Network
name: Jason Lickliter, MD
role: PRINCIPAL_INVESTIGATOR
References: