Study Evaluating the Pharmacokinetics of Mavacamten in Healthy Adult Chinese Subjects

Phase 1

Completed

Brief Summary: 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: 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)

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Cohort 1: Mavacamten 15 mg	Mavacamten	Cohort 1: 15 mg capsules × 1 on Day 1
Cohort 2: Mavacamten 25 mg	Mavacamten	Cohort 2: 10 mg capsules x 1 and 15 mg capsules x 1 on Day 1
Cohort 3: Mavacamten 15 mg	Mavacamten	Cohort 3: 15 mg capsules × 1 on Day 1
Cohort 4: Mavacamten 15 mg	Mavacamten	Cohort 4: 15 mg capsules × 1 on Day 1

Primary Outcome Measures

Name	Time	Method
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	Determination of pharmacokinetics parameters as measured by maximum concentration (Cmax)
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	Determination of pharmacokinetics parameters as measured by time to maximum concentration (Tmax)
Area Under the 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	Determination of pharmacokinetics parameters as measured by area under curve AUC(0-last), AUC(0-inf)
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	Determination of pharmacokinetics parameters as measured by elimination half-life (T1⁄2)
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	Determination of pharmacokinetics parameters as measured by apparent volume of distribution (Vd/F)
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	Determination of pharmacokinetics parameters as measured by apparent clearance (CL/F)

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	Up to 75 days	Safety assessments will be performed by incidence of adverse events during the whole study at specified time points
Body Weight at Screening and EOS	Body weight (kg) will be measured at screening (baseline) and EOS(75 days).	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.
Physical Examination Findings	Up to 75 days	Safety assessments will be performed by physical examination findings during the whole study at specified time points
Heart Rate at Baseline and Day 75	Up to 75 days	Safety assessments will be performed by electrocardiogram (ECG) parameters findings during the whole study at specified time points
Clinical Laboratory Tests Data	Up to 75 days	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