Study Evaluating the Pharmacokinetics of Mavacamten in Healthy Adult Chinese Subjects

LianBio

Status and phase: Completed; Phase 1

Conditions: Hypertrophic Cardiomyopathy

Treatments: Drug: Mavacamten

Study type: Interventional

Funder types: Industry

Identifiers

NCT05135871

LB2001-101

Details and patient eligibility

About

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.

Full 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)

Enrollment: 45 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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45 participants in 4 patient groups

Cohort 1: Mavacamten 15 mg

Experimental group

Description:

Cohort 1: 15 mg capsules × 1 on Day 1

Treatment:

Drug: Mavacamten

Cohort 2: Mavacamten 25 mg

Experimental group

Description:

Cohort 2: 10 mg capsules x 1 and 15 mg capsules x 1 on Day 1

Treatment:

Drug: Mavacamten

Cohort 3: Mavacamten 15 mg

Experimental group

Description:

Cohort 3: 15 mg capsules × 1 on Day 1

Treatment:

Drug: Mavacamten

Cohort 4: Mavacamten 15 mg

Experimental group

Description:

Cohort 4: 15 mg capsules × 1 on Day 1

Treatment:

Drug: Mavacamten