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.
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)
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
45
Single fasted oral dose of Mavacamten 15/25 mg on Day 1
Huashan Hospital Fudan University
Shanghai, Shanghai Municipality, China
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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: Predose, Day 1, Day 7, Day 10, Day 14, Day 21, Day 28, Day 35, Day 45, Day 67 and Day 75 post-dose
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Number of Participants With Adverse Events
Safety assessments will be performed by incidence of adverse events during the whole study at specified time points
Time frame: Up to 75 days
Body Weight at Screening and EOS
Safety assessments will be performed by vital signs during the whole study at screening, Day-1, Day 3 and at the EOS Visit. A complete physical examination includes assessments of general appearance, skin, head and neck, chest, abdomen, back, spine, extremity neurological, and mental systems. Brief physical examination means chest examinations. Height (cm) and body weight (kg) will be measured at screening, and BMI (kg/m2) will be calculated. Body weight (kg) will be measured at EOS. The mean weight and the standard deviation are analysis for different cohort.
Time frame: Body weight (kg) will be measured at screening (baseline) and EOS(75 days).
Physical Examination Findings
Safety assessments will be performed by physical examination findings during the whole study at specified time points
Time frame: Up to 75 days
Heart Rate at Baseline and Day 75
Safety assessments will be performed by electrocardiogram (ECG) parameters findings during the whole study at specified time points
Time frame: 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
Time frame: Up to 75 days