Study Evaluating the Pharmacokinetics of Mavacamten in Healthy Adult Chinese Subjects

• Status: Recruiting
• Trial end date: 2022-06-30
• Target enrollment: 0
• Participant gender: All

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 CYP2C19 genotypes (Cohort 1 and Cohort 2: CYP2C19 UM, RM, or NM; Cohort 3: CYP2C19 IM; Cohort 4: CYP2C19 PM) 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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: LianBio LLC

Criteria

Inclusion Criteria:

• Male or female between the ages of 18 and 60 (inclusive) at screening (one sex not less than 25% each cohort)

• Subjects who are CYP2C19 UM (*17/*17), CYP2C19 RM (*1/*17), CYP2C19 NM (*1/*1), CYP2C19 IM (*1/*2 or *1/*3) or CYP2C19 PM (*2/*2, *3/*3, or *2/*3) as per central laboratory phenotype interpretation during the pre-screening period

• With a body mass index (BMI) between 18 kg/m2 and 30 kg/m2 (inclusive) at screening

• With a resting left ventricular ejection fraction (LVEF) ≥ 55% by echocardiography at screening

• Healthy as determined by medical history, physical examination, vital signs, and laboratory tests (chemistry, hematology, coagulation and urinalysis), and 12-lead ECG at screening and on Day -1. Laboratory values outside the normal range are acceptable if such abnormalities are interpreted as being clinically insignificant. Screening assessments can be repeated for one more time at the investigator's discretion within the screening window

• Female subjects shall not be pregnant or breastfeeding and, if sexually active with male partner(s), must adopt one of the following highly effective contraceptive methods from the Screening Visit through 5 months after administration of the investigational medicinal product (IMP):

1. Estrogen and progesterone containing hormonal contraception associated with inhibition of ovulation or progesterone only hormonal contraception associated with inhibition of ovulation by oral, implantable, or injectable routes of administration

2. Intrauterine device (IUD)

3. Intrauterine system (IUS)

4. Bilateral tubal ligation

5. Females who have been surgically sterilized for more than 6 months or postmenopausal for more than 1 year. Permanent sterilization includes hysterectomy, bilateral oophorectomy, bilateral salpingectomy, and/or documented bilateral tubal ligation for at least 6 months prior to screening. Females are considered postmenopausal if they have had amenorrhea for at least 1 year or more following cessation of all exogenous hormonal treatments and their follicle stimulating hormone levels are in the postmenopausal range

• Male partners of female subjects must also adopt a contraceptive method (e.g., barrier, condom or vasectomy) 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

Exclusion Criteria:

• History of clinically significant arrhythmia, left ventricular (LV) systolic dysfunction, or coronary artery disease, or QTc >450 ms at screening and on Day -1

• History of any type of malignant tumors, other than in situ cervical cancer or surgically excised non melanomatous skin cancers, 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

• Vital sign meet any of the following criteria:

1. ear temperature was greater than 37.5 ℃

2. heart rate was greater than 100 beats / min or less than 50 beats / min

3. systolic blood pressure was greater than 139 mmHg or less than 90 mmHg

4. diastolic blood pressure was greater than 90 mmHg or less than 50 mmHg at screening and on Day -1

• Subjects who have taken prescription medications within 28 days prior to screening or within 5 times of T1/2 (if known), whichever is longer; or those who have taken over-the-counter medications (including herbal preparations and nutritional supplements) within 14 days prior to screening or within 5 times of T1/2 (if known), whichever is longer (acetaminophen up to 1.5 g per day is allowed)

• 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 exceeding 10 cigarettes per day or nicotine-containing products of equivalent amount within 28 days prior to screening

• Hypersensitivity to mavacamten or any of the components of its formulation (Inactive ingredients are silicon dioxide, mannitol, hypromellose, croscarmellose sodium, and magnesium stearate (non-bovine). The capsule contains gelatin, titanium dioxide, black iron oxide, red iron oxide, and yellow iron oxide)

• Prior exposure to mavacamten

• Prior exposure to the investigational drug (or current use of an investigational device) within 30 days prior to screening, or at least 5 times of T1/2 (if known), whichever is longer

• Unable to comply with the study restrictions/requirements, including the number of required visits to the clinical site

• Had donated over or lost 400 mL blood in 60 days or plasma in the last 2 weeks prior to the screening visit

• Infection of coronavirus disease 2019 (COVID-19) (i.e., positive for polymerase chain reaction) within 6 months prior to screening

• Unsuitable to participate in the study as judged by the investigator