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.

Study Overview

• Status: Completed
• Conditions: Dilated Cardiomyopathy
• Intervention / Treatment: Drug: MYK-491 or placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Nucleus Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single oral dose of MYK-491; single-dose, oral suspension	Drug: MYK-491 or placebo; Oral suspension
PLACEBO_COMPARATOR: Single oral dose of placebo; single-dose, oral suspension	Drug: MYK-491 or placebo; Oral suspension

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
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
Relationship between MYK-491 plasma concentration and QTc interval	7 days

Collaborators and Investigators

• Sponsor: MyoKardia, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 16, 2017
• Primary Completion (ACTUAL): November 28, 2017
• Study Completion (ACTUAL): November 28, 2017

Study Registration Dates

• First Submitted: February 16, 2017
• First Submitted That Met QC Criteria: February 20, 2017
• First Posted (ACTUAL): February 24, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 23, 2018
• Last Update Submitted That Met QC Criteria: March 21, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Cardiomegaly; Laminopathies; Cardiomyopathies; Cardiomyopathy, Dilated
• Other Study ID Numbers: MYK-491-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No