Safety, Tolerability and Pharmacokinetics Study of CK-3773274

Study Overview
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Brief Summary
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The purposes of this study are to: Learn about the safety of CK-3773274 after a single dose and multiple doses in Chinese healthy adult subjects. Learn how healthy subjects tolerate CK-3773274 after a single dose and multiple doses. Find out how much CK-3773274 is in the blood after a single dose and multiple doses. Determine the effect of doses of CK-3773274 on the pumping function of the heart. Evaluate the effect CYP2D6 genetic polymorphisms on how the body metabolizes CK-3773274.

Official Title
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A Phase 1, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Safety, Tolerability and Pharmacokinetics of CK-3773274 in Healthy Chinese Subjects

Conditions
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Obstructive Hypertrophic Cardiomyopathy, Healthy Adult Subjects

Intervention / Treatment
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* Drug: CK-3773274
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Chinese males and females between 18 and 45 years of age, inclusive Body weight ≥50kg and body mass index (BMI) within 18 to 26 kg/m2, inclusive Acoustic windows adequate for accurate transthoracic echocardiograms Normal cardiac structure and function, as determined by the cardiologist, or if abnormalities are present, the finding is not clinically significant as determined by the cardiologist LVEF ≥65 percent at screening, and LVEF ≥60 percent at Day-1 Normal ECG Exclusion Criteria: History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs Subjects with breast implants that may impede echocardiography A clinically significant illness within 4 weeks prior to admission to the CRU Inability to swallow tablets Use of alcohol-containing, grapefruit-containing, or caffeine-containing foods or beverages within 48 hours prior to admission to the CRU Poor peripheral venous access Any blood donation within 60 days prior to admission to the CRU, or any plasma donation within 30 days prior to admission to the CRU, or receipt of blood products within 2 months prior to admission to the CRU

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CK-3773274 for Single Ascending Dose (SAD) Cohorts<br>Subjects will be assigned to one of 2 planned dose cohorts and receive single doses of CK-3773274 | Drug: CK-3773274<br>* CK-3773274- Tablets<br>|
| Placebo Comparator: Placebo comparator for SAD Cohorts<br>Subjects will be assigned to one of 2 planned dose cohorts and receive single doses of placebo comparator | Drug: Placebo<br>* Placebo- Tablets<br>|
| Experimental: CK-3773274 for Multiple Dose (MD) Cohort<br>Subjects will receive multiple doses of CK-3773274 | Drug: CK-3773274<br>* CK-3773274- Tablets<br>|
| Placebo Comparator: Placebo comparator for MD Cohort<br>Subjects will receive multiple doses of placebo comparator | Drug: Placebo<br>* Placebo- Tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject incidence of Adverse Event (AE), Serious Adverse Event (SAE) |  | SAD cohorts: Day-1 - Day10; MD cohort: Day-1 - Day 23 | 
| Reduced Left Ventricular Ejection Fraction (LVEF) |  | SAD cohorts: Day-1 - Day10; MD cohort: Day-1 - Day 23 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of CK-3773274 after single and multiple ascending doses |  | SAD Cohorts: Day-1 - Day10; MD Cohort: Day-1 - Day 23 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oHCM, CK-274, Obstructive hypertrophic cardiomyopathy, CK-3773274