Study Evaluating the Pharmacokinetics of Mavacamten in Healthy Adult Chinese Subjects

Study Overview
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Brief Summary
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Mavacamten is a small-molecule allosteric inhibitor of cardiac myosin that reversibly inhibits its binding to cardiac actin, thereby relieving systolic hypercontractility and improving ventricular compliance. This is an open-label, parallel-group, single-center Phase 1 clinical study. Healthy adult Chinese subjects with different genotypes will be included and administered with a single fasted oral dose of mavacamten to evaluate its PK profile. Up to 44 subjects will be enrolled in this study.

Detailed Description
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Approximately 44 healthy adult Chinese subjects are expected to be enrolled in this study according to their genotypes into 4 cohorts. The doses administered include: 15 mg for cohort 1; 25 mg for Cohort 2; 15 mg for Cohort 3; 15 mg for Cohort 4. Blood samples will be collected from subjects at scheduled time points for PK testing. Series of safety assessments (including but not limited to AEs, laboratory tests, vital signs, and ECGs) will be performed during the whole study at specified time points. This study will consist of the following 5 periods: Pre-screening period and Screening period (Day -43 to Day -2, up to 42 days) In-house period (Day -1 to Day 3, total 4 days) Outpatient period (Day 4 to Day 75, total 72 days): End of study visit (Day 75)

Official Title
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An Open-Label, Parallel-Group, Single-Center Phase 1 Clinical Study to Evaluate the Pharmacokinetics of a Single Oral Dose of Mavacamten in Healthy Adult Chinese Subjects

Conditions
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Hypertrophic Cardiomyopathy

Intervention / Treatment
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* Drug: Mavacamten


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female between the ages of 18 and 60 (inclusive) at screening With a body mass index (BMI) between 18 kg/m2 and 30 kg/m2 (inclusive) at screening Healthy as determined at screening and on Day -1 Female subjects shall not be pregnant or breastfeeding Male partners of female subjects must also adopt a contraceptive method from screening through 5 months after administration of the investigational drug Able to understand and comply with the study procedures, understand the risks involved in this study, and provide written informed consent according to local and institutional guidelines before screening procedure Key Exclusion Criteria: History of clinically significant arrhythmia History of any type of malignant tumors within 5 years of the Screening Visit Positive serologic tests at screening for infections with human immunodeficiency virus (HIV) antibody, hepatitis C virus (HCV) antibody or hepatitis B virus (HBV) surface antigen at screening The vital signs of screening period and Day -1 were unqualified Subjects who have taken prescription medications within 28 days prior to screening or within 5 times of T1/2 (if known), whichever is longer History or evidence of any other clinically significant abnormalities, conditions, or diseases that, in the opinion of the investigator, would pose a risk to the safety of the subject or interfere with study evaluation, procedures, or its completion Any condition or treatment for a condition that might interfere with the conduct of the trial or might, in the opinion of the investigator, put the subject at risk, including but not limited to, alcoholism, drug dependence or abuse, and psychiatric conditions, if he/she participates in this study Positive test for alcohol or drug abuse at screening and on Day -1 Use of tobacco within 28 days prior to screening Hypersensitivity to mavacamten or any of the components of its formulation Prior exposure to mavacamten Unable to comply with the study restrictions/requirements, including the number of required visits to the clinical site Unsuitable to participate in the study as judged by the investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Mavacamten 15 mg<br>Cohort 1: 15 mg capsules × 1 on Day 1 | Drug: Mavacamten<br>* Single fasted oral dose of Mavacamten 15/25 mg on Day 1<br>* Other names: Mavacamten capsule;|
| Experimental: Cohort 2: Mavacamten 25 mg<br>Cohort 2: 10 mg capsules x 1 and 15 mg capsules x 1 on Day 1 | Drug: Mavacamten<br>* Single fasted oral dose of Mavacamten 15/25 mg on Day 1<br>* Other names: Mavacamten capsule;|
| Experimental: Cohort 3: Mavacamten 15 mg<br>Cohort 3: 15 mg capsules × 1 on Day 1 | Drug: Mavacamten<br>* Single fasted oral dose of Mavacamten 15/25 mg on Day 1<br>* Other names: Mavacamten capsule;|
| Experimental: Cohort 4: Mavacamten 15 mg<br>Cohort 4: 15 mg capsules × 1 on Day 1 | Drug: Mavacamten<br>* Single fasted oral dose of Mavacamten 15/25 mg on Day 1<br>* Other names: Mavacamten capsule;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve (AUC) (0-last), AUC(0-inf) | Determination of pharmacokinetics parameters as measured by area under curve AUC(0-last), AUC(0-inf) | Predose, Day 1, Day 7, Day 10, Day 14, Day 21, Day 28, Day 35, Day 45, Day 67 and Day 75 post-dose | 
| Maximum concentration (Cmax) | Determination of pharmacokinetics parameters as measured by maximum concentration (Cmax) | Predose, Day 1, Day 7, Day 10, Day 14, Day 21, Day 28, Day 35, Day 45, Day 67 and Day 75 post-dose | 
| Time to maximum concentration (Tmax) | Determination of pharmacokinetics parameters as measured by time to maximum concentration (Tmax) | Predose, Day 1, Day 7, Day 10, Day 14, Day 21, Day 28, Day 35, Day 45, Day 67 and Day 75 post-dose | 
| Elimination half-life (T1⁄2) | Determination of pharmacokinetics parameters as measured by elimination half-life (T1⁄2) | Predose, Day 1, Day 7, Day 10, Day 14, Day 21, Day 28, Day 35, Day 45, Day 67 and Day 75 post-dose | 
| Apparent volume of distribution (Vd/F) | Determination of pharmacokinetics parameters as measured by apparent volume of distribution (Vd/F) | Predose, Day 1, Day 7, Day 10, Day 14, Day 21, Day 28, Day 35, Day 45, Day 67 and Day 75 post-dose | 
| Apparent clearance (CL/F) | Determination of pharmacokinetics parameters as measured by apparent clearance (CL/F) | Predose, Day 1, Day 7, Day 10, Day 14, Day 21, Day 28, Day 35, Day 45, Day 67 and Day 75 post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events | Safety assessments will be performed by incidence of adverse events during the whole study at specified time points | Up to 75 days | 
| Vital signs | Safety assessments will be performed by vital signs during the whole study at specified time points | Up to 75 days | 
| Physical examination findings | Safety assessments will be performed by physical examination findings during the whole study at specified time points | Up to 75 days | 
| Electrocardiogram (ECG) parameters | Safety assessments will be performed by electrocardiogram (ECG) parameters findings during the whole study at specified time points | Up to 75 days | 
| Clinical laboratory tests data | Safety assessments will be performed by clinical laboratory tests data(including hematology and blood chemistry, coagulation and urinalysis parameters) during the whole study at specified time points | Up to 75 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mavacamten