Study Evaluating the Pharmacokinetics of Mavacamten in Healthy Adult Chinese Subjects

NCT05135871 | Completed Phase 1 Results FDA Drug

• 1 other identifier: LB2001-101
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertrophic Cardiomyopathy

Keywords

Mavacamten

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (5)

• Number of Participants With Adverse Events

  Up to 75 days

• Body Weight at Screening and EOS

  Body weight (kg) will be measured at screening (baseline) and EOS(75 days).

• Physical Examination Findings

  Up to 75 days

• Heart Rate at Baseline and Day 75

  Up to 75 days

• Clinical Laboratory Tests Data

  Up to 75 days

Study Arms (4)

Cohort 1: Mavacamten 15 mg

EXPERIMENTAL

Cohort 1: 15 mg capsules × 1 on Day 1

Drug: Mavacamten

Cohort 2: Mavacamten 25 mg

EXPERIMENTAL

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

Drug: Mavacamten

Cohort 3: Mavacamten 15 mg

EXPERIMENTAL

Cohort 3: 15 mg capsules × 1 on Day 1

Drug: Mavacamten

Cohort 4: Mavacamten 15 mg

EXPERIMENTAL

Cohort 4: 15 mg capsules × 1 on Day 1

Drug: Mavacamten

Interventions

Mavacamten DRUG

Single fasted oral dose of Mavacamten 15/25 mg on Day 1

Also known as: Mavacamten capsule

Cohort 1: Mavacamten 15 mg; Cohort 2: Mavacamten 25 mg; Cohort 3: Mavacamten 15 mg; Cohort 4: Mavacamten 15 mg

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• LianBio LLC: lead

Study Sites (1)

Huashan Hospital Fudan University

Shanghai, Shanghai Municipality, 200040, China

Location

Related Publications (1)

• Wu X, Chen N, Hsu P, Sun J, Li W, Wang Q, Samira M, Wei Q, Yu J, Cao G, Yang H, Wang L, Wang J, Jin Y, Liu W, Wu J, He J, Lyu C, Zhang J. Pharmacokinetics and safety of mavacamten in healthy Chinese participants with different CYP2C19 phenotypes. Clin Transl Sci. 2024 Jul;17(7):e13877. doi: 10.1111/cts.13877.

  PMID: 39014868 DERIVED

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic

Interventions

MYK-461

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Limitations and Caveats

There are no special limitations and caveats to this trial.

Results Point of Contact

• Title: Brianna Sun
• Organization: Shanghai LianBio Development Co., Ltd

brianna.sun@lianbio.com

+862123081188

Study Officials

• Jing Zhang, Doctor

  Huashan Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2021
• First Posted: November 26, 2021
• Study Start: October 31, 2021
• Primary Completion: February 5, 2022
• Study Completion: February 28, 2022
• Last Updated: July 25, 2024
• Results First Posted: July 25, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)