An Open-Label, Parallel-Group, Single-Center Phase 1 Clinical Study to Evaluate the Pharmacokinetics of a Single Oral Dose of Mavacamten in Healthy Adult Chinese Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- LianBio LLC
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Maximum Concentration (Cmax)
研究概览
简要总结
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.
详细描述
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Cohort 1: Mavacamten 15 mg
Cohort 1: 15 mg capsules × 1 on Day 1
干预措施: Mavacamten (Drug)
Cohort 2: Mavacamten 25 mg
Cohort 2: 10 mg capsules x 1 and 15 mg capsules x 1 on Day 1
干预措施: Mavacamten (Drug)
Cohort 3: Mavacamten 15 mg
Cohort 3: 15 mg capsules × 1 on Day 1
干预措施: Mavacamten (Drug)
Cohort 4: Mavacamten 15 mg
Cohort 4: 15 mg capsules × 1 on Day 1
干预措施: Mavacamten (Drug)
结局指标
主要结局
Maximum Concentration (Cmax)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
次要结局
- 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)