Hypertrophic Cardiomyopathy
Conditions
Keywords
Mavacamten
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)
Interventions
DRUGMavacamten
Single fasted oral dose of Mavacamten 15/25 mg on Day 1
Sponsors
LianBio LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| 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) |
| 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) |
| 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Mavacamten 15 mg Cohort 1: 15 mg capsules × 1 on Day 1
Mavacamten: Single fasted oral dose of Mavacamten 15 mg on Day 1 | 12 |
| Cohort 2: Mavacamten 25 mg Cohort 2: 10 mg capsules x 1 and 15 mg capsules x 1 on Day 1
Mavacamten: Single fasted oral dose of Mavacamten 25 mg on Day 1 13 subjects were assigned to Cohort 2 but 1 subject (Cohort 2) withdrew from the study before administration of the study drug due to pre-dose abnormal ECG and was excluded from the pharmacokinetic analysis set and safety analysis set. | 12 |
| Cohort 3: Mavacamten 15 mg Cohort 3: 15 mg capsules × 1 on Day 1
Mavacamten: Single fasted oral dose of Mavacamten 15 mg on Day 1 | 12 |
| Cohort 4: Mavacamten 15 mg Cohort 4: 15 mg capsules × 1 on Day 1
Mavacamten: Single fasted oral dose of Mavacamten 15 mg on Day 1 | 8 |
| Total | 44 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | 1 subject withdrew from the study before administration of the IMP due to pre-dose abnormal ECG | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 2: Mavacamten 25 mg | Total | Cohort 1: Mavacamten 15 mg | Cohort 4: Mavacamten 15 mg | Cohort 3: Mavacamten 15 mg |
|---|---|---|---|---|---|
| Age, Continuous | 31.0 years STANDARD_DEVIATION 7.12 | 30.1 years STANDARD_DEVIATION 6.44 | 26.8 years STANDARD_DEVIATION 4.99 | 35.4 years STANDARD_DEVIATION 4.31 | 28.9 years STANDARD_DEVIATION 6.32 |
| Body mass index | 23.82 kg/m^2 STANDARD_DEVIATION 2.571 | 23.67 kg/m^2 STANDARD_DEVIATION 2.421 | 24.34 kg/m^2 STANDARD_DEVIATION 2.444 | 23.04 kg/m^2 STANDARD_DEVIATION 2.312 | 23.26 kg/m^2 STANDARD_DEVIATION 2.434 |
| CYP2C19 genotype Intermediate metabolizer | 0 Participants | 12 Participants | 0 Participants | 0 Participants | 12 Participants |
| CYP2C19 genotype Normal metabolizer | 11 Participants | 22 Participants | 11 Participants | 0 Participants | 0 Participants |
| CYP2C19 genotype Poor metabolizer | 0 Participants | 8 Participants | 0 Participants | 8 Participants | 0 Participants |
| CYP2C19 genotype Rapid metabolizer | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants |
| CYP2C19 genotype Ultra-rapid metabolizer | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Left ventricular ejection fraction(%) | 66.9 % STANDARD_DEVIATION 396 | 66.5 % STANDARD_DEVIATION 4.63 | 68.0 % STANDARD_DEVIATION 5.03 | 64.0 % STANDARD_DEVIATION 5.58 | 66.4 % STANDARD_DEVIATION 3.99 |
| Race/Ethnicity, Customized Chinese | 12 Participants | 44 Participants | 12 Participants | 8 Participants | 12 Participants |
| Race/Ethnicity, Customized Han | 12 Participants | 44 Participants | 12 Participants | 8 Participants | 12 Participants |
| Race/Ethnicity, Customized Non-Chinese | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Non-Han | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 12 participants | 44 participants | 12 participants | 8 participants | 12 participants |
| Sex: Female, Male Female | 3 Participants | 11 Participants | 3 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 9 Participants | 33 Participants | 9 Participants | 6 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 8 |
| other Total, other adverse events | 3 / 12 | 6 / 12 | 9 / 12 | 3 / 8 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 8 |
Outcome results
Primary
Apparent Clearance (CL/F)
Determination of pharmacokinetics parameters as measured by apparent clearance (CL/F)
Time frame: Predose, Day 1, Day 7, Day 10, Day 14, Day 21, Day 28, Day 35, Day 45, Day 67 and Day 75 post-dose
Population: One subject (Cohort 3) was excluded from the pharmacokinetic analysis set due to a major protocol deviation (use of prohibited drug moderate-acting CYP2C19 inhibitor Omeprazole) affecting the assessment of PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Mavacamten 15 mg | Apparent Clearance (CL/F) | 1495 mL/h | Standard Deviation 35.44 |
| Cohort 2: Mavacamten 25 mg | Apparent Clearance (CL/F) | 1233 mL/h | Standard Deviation 52.47 |
| Cohort 3: Mavacamten 15 mg | Apparent Clearance (CL/F) | 814.0 mL/h | Standard Deviation 21.18 |
| Cohort 4: Mavacamten 15 mg | Apparent Clearance (CL/F) | 327.5 mL/h | Standard Deviation 25.51 |
Primary
Apparent Volume of Distribution (Vd/F)
Determination of pharmacokinetics parameters as measured by apparent volume of distribution (Vd/F)
Time frame: Predose, Day 1, Day 7, Day 10, Day 14, Day 21, Day 28, Day 35, Day 45, Day 67 and Day 75 post-dose
Population: One subject (Cohort 3) was excluded from the pharmacokinetic analysis set due to a major protocol deviation (use of prohibited drug moderate-acting CYP2C19 inhibitor Omeprazole) affecting the assessment of PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Mavacamten 15 mg | Apparent Volume of Distribution (Vd/F) | 259500 mL | Standard Deviation 29.93 |
| Cohort 2: Mavacamten 25 mg | Apparent Volume of Distribution (Vd/F) | 255300 mL | Standard Deviation 16.6 |
| Cohort 3: Mavacamten 15 mg | Apparent Volume of Distribution (Vd/F) | 241200 mL | Standard Deviation 23.13 |
| Cohort 4: Mavacamten 15 mg | Apparent Volume of Distribution (Vd/F) | 270200 mL | Standard Deviation 26.95 |
Primary
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)
Time frame: Predose, Day 1, Day 7, Day 10, Day 14, Day 21, Day 28, Day 35, Day 45, Day 67 and Day 75 post-dose
Population: One subject (Cohort 3) was excluded from the pharmacokinetic analysis set due to a major protocol deviation (use of prohibited drug moderate-acting CYP2C19 inhibitor Omeprazole) affecting the assessment of PK parameters.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Mavacamten 15 mg | Area Under the Curve (AUC) (0-last), AUC(0-inf) | (AUC) (0-last) | 9956 h*ng/mL | Standard Deviation 35.61 |
| Cohort 1: Mavacamten 15 mg | Area Under the Curve (AUC) (0-last), AUC(0-inf) | AUC(0-inf) | 10030 h*ng/mL | Standard Deviation 35.44 |
| Cohort 2: Mavacamten 25 mg | Area Under the Curve (AUC) (0-last), AUC(0-inf) | AUC(0-inf) | 20280 h*ng/mL | Standard Deviation 52.47 |
| Cohort 2: Mavacamten 25 mg | Area Under the Curve (AUC) (0-last), AUC(0-inf) | (AUC) (0-last) | 20040 h*ng/mL | Standard Deviation 50.49 |
| Cohort 3: Mavacamten 15 mg | Area Under the Curve (AUC) (0-last), AUC(0-inf) | (AUC) (0-last) | 18270 h*ng/mL | Standard Deviation 21.05 |
| Cohort 3: Mavacamten 15 mg | Area Under the Curve (AUC) (0-last), AUC(0-inf) | AUC(0-inf) | 18430 h*ng/mL | Standard Deviation 21.18 |
| Cohort 4: Mavacamten 15 mg | Area Under the Curve (AUC) (0-last), AUC(0-inf) | (AUC) (0-last) | 39980 h*ng/mL | Standard Deviation 23.6 |
| Cohort 4: Mavacamten 15 mg | Area Under the Curve (AUC) (0-last), AUC(0-inf) | AUC(0-inf) | 45810 h*ng/mL | Standard Deviation 25.51 |
Primary
Elimination Half-life (T1⁄2)
Determination of pharmacokinetics parameters as measured by elimination half-life (T1⁄2)
Time frame: Predose, Day 1, Day 7, Day 10, Day 14, Day 21, Day 28, Day 35, Day 45, Day 67 and Day 75 post-dose
Population: One subject (Cohort 3) was excluded from the pharmacokinetic analysis set due to a major protocol deviation (use of prohibited drug moderate-acting CYP2C19 inhibitor Omeprazole) affecting the assessment of PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Mavacamten 15 mg | Elimination Half-life (T1⁄2) | 120.3 h | Standard Deviation 23.44 |
| Cohort 2: Mavacamten 25 mg | Elimination Half-life (T1⁄2) | 143.6 h | Standard Deviation 42.32 |
| Cohort 3: Mavacamten 15 mg | Elimination Half-life (T1⁄2) | 205.4 h | Standard Deviation 22.31 |
| Cohort 4: Mavacamten 15 mg | Elimination Half-life (T1⁄2) | 572.0 h | Standard Deviation 25.03 |
Primary
Maximum Concentration (Cmax)
Determination of pharmacokinetics parameters as measured by maximum concentration (Cmax)
Time frame: Predose, Day 1, Day 7, Day 10, Day 14, Day 21, Day 28, Day 35, Day 45, Day 67 and Day 75 post-dose
Population: One subject (Cohort 3) was excluded from the pharmacokinetic analysis set due to a major protocol deviation (use of prohibited drug moderate-acting CYP2C19 inhibitor Omeprazole) affecting the assessment of PK parameters.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Mavacamten 15 mg | Maximum Concentration (Cmax) | 395.4 ng/mL | Standard Deviation 39.95 |
| Cohort 2: Mavacamten 25 mg | Maximum Concentration (Cmax) | 571.8 ng/mL | Standard Deviation 25.69 |
| Cohort 3: Mavacamten 15 mg | Maximum Concentration (Cmax) | 485.2 ng/mL | Standard Deviation 34.96 |
| Cohort 4: Mavacamten 15 mg | Maximum Concentration (Cmax) | 435.7 ng/mL | Standard Deviation 35.66 |
Primary
Time to Maximum Concentration (Tmax)
Determination of pharmacokinetics parameters as measured by time to maximum concentration (Tmax)
Time frame: Predose, Day 1, Day 7, Day 10, Day 14, Day 21, Day 28, Day 35, Day 45, Day 67 and Day 75 post-dose
Population: One subject (Cohort 3) was excluded from the pharmacokinetic analysis set due to a major protocol deviation (use of prohibited drug moderate-acting CYP2C19 inhibitor Omeprazole) affecting the assessment of PK parameters.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Mavacamten 15 mg | Time to Maximum Concentration (Tmax) | 0.88 h |
| Cohort 2: Mavacamten 25 mg | Time to Maximum Concentration (Tmax) | 1.50 h |
| Cohort 3: Mavacamten 15 mg | Time to Maximum Concentration (Tmax) | 0.75 h |
| Cohort 4: Mavacamten 15 mg | Time to Maximum Concentration (Tmax) | 0.63 h |
Secondary
Body Weight at Screening and EOS
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.
Time frame: Body weight (kg) will be measured at screening (baseline) and EOS(75 days).
Population: All 44 subjects included in the safety analysis set: cohort 1 12 subjects, cohort 2 12 subjects, cohort 3 12 subjects, cohort 4 8 subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Mavacamten 15 mg | Body Weight at Screening and EOS | Change from Baseline | 0.80 kg | Standard Deviation 2.899 |
| Cohort 1: Mavacamten 15 mg | Body Weight at Screening and EOS | Day 75 | 70.21 kg | Standard Deviation 13.088 |
| Cohort 1: Mavacamten 15 mg | Body Weight at Screening and EOS | Baseline | 69.41 kg | Standard Deviation 12.699 |
| Cohort 2: Mavacamten 25 mg | Body Weight at Screening and EOS | Change from Baseline | 0.70 kg | Standard Deviation 1.738 |
| Cohort 2: Mavacamten 25 mg | Body Weight at Screening and EOS | Day 75 | 63.48 kg | Standard Deviation 9.405 |
| Cohort 2: Mavacamten 25 mg | Body Weight at Screening and EOS | Baseline | 62.78 kg | Standard Deviation 8.458 |
| Cohort 3: Mavacamten 15 mg | Body Weight at Screening and EOS | Baseline | 65.89 kg | Standard Deviation 11.157 |
| Cohort 3: Mavacamten 15 mg | Body Weight at Screening and EOS | Change from Baseline | -0.36 kg | Standard Deviation 2.378 |
| Cohort 3: Mavacamten 15 mg | Body Weight at Screening and EOS | Day 75 | 65.53 kg | Standard Deviation 10.929 |
| Cohort 4: Mavacamten 15 mg | Body Weight at Screening and EOS | Change from Baseline | 1.25 kg | Standard Deviation 2.184 |
| Cohort 4: Mavacamten 15 mg | Body Weight at Screening and EOS | Day 75 | 69.51 kg | Standard Deviation 11.53 |
| Cohort 4: Mavacamten 15 mg | Body Weight at Screening and EOS | Baseline | 68.26 kg | Standard Deviation 11.147 |
Secondary
Clinical Laboratory Tests Data
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
Time frame: Up to 75 days
Population: All 44 subjects included in the safety analysis set: cohort 1 12 subjects, cohort 2 12 subjects, cohort 3 12 subjects, cohort 4 8 subjects.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Mavacamten 15 mg | Clinical Laboratory Tests Data | Hemoglobin decreased | 0 participants |
| Cohort 1: Mavacamten 15 mg | Clinical Laboratory Tests Data | Blood fibrinogen increased | 0 participants |
| Cohort 1: Mavacamten 15 mg | Clinical Laboratory Tests Data | Eosinophil count increased | 0 participants |
| Cohort 1: Mavacamten 15 mg | Clinical Laboratory Tests Data | Neutrophil count increased | 0 participants |
| Cohort 1: Mavacamten 15 mg | Clinical Laboratory Tests Data | Eosinophil percentage increased | 0 participants |
| Cohort 1: Mavacamten 15 mg | Clinical Laboratory Tests Data | White blood cell count decreased | 0 participants |
| Cohort 1: Mavacamten 15 mg | Clinical Laboratory Tests Data | White blood cell count increased | 0 participants |
| Cohort 1: Mavacamten 15 mg | Clinical Laboratory Tests Data | Neutrophil count decreased | 0 participants |
| Cohort 1: Mavacamten 15 mg | Clinical Laboratory Tests Data | Urobilinogen urine increased | 0 participants |
| Cohort 1: Mavacamten 15 mg | Clinical Laboratory Tests Data | Alanine aminotransferase increased | 0 participants |
| Cohort 2: Mavacamten 25 mg | Clinical Laboratory Tests Data | Alanine aminotransferase increased | 0 participants |
| Cohort 2: Mavacamten 25 mg | Clinical Laboratory Tests Data | Eosinophil percentage increased | 0 participants |
| Cohort 2: Mavacamten 25 mg | Clinical Laboratory Tests Data | Hemoglobin decreased | 0 participants |
| Cohort 2: Mavacamten 25 mg | Clinical Laboratory Tests Data | Eosinophil count increased | 0 participants |
| Cohort 2: Mavacamten 25 mg | Clinical Laboratory Tests Data | White blood cell count decreased | 1 participants |
| Cohort 2: Mavacamten 25 mg | Clinical Laboratory Tests Data | White blood cell count increased | 1 participants |
| Cohort 2: Mavacamten 25 mg | Clinical Laboratory Tests Data | Neutrophil count increased | 0 participants |
| Cohort 2: Mavacamten 25 mg | Clinical Laboratory Tests Data | Blood fibrinogen increased | 0 participants |
| Cohort 2: Mavacamten 25 mg | Clinical Laboratory Tests Data | Neutrophil count decreased | 0 participants |
| Cohort 2: Mavacamten 25 mg | Clinical Laboratory Tests Data | Urobilinogen urine increased | 0 participants |
| Cohort 3: Mavacamten 15 mg | Clinical Laboratory Tests Data | Hemoglobin decreased | 0 participants |
| Cohort 3: Mavacamten 15 mg | Clinical Laboratory Tests Data | Blood fibrinogen increased | 1 participants |
| Cohort 3: Mavacamten 15 mg | Clinical Laboratory Tests Data | White blood cell count decreased | 0 participants |
| Cohort 3: Mavacamten 15 mg | Clinical Laboratory Tests Data | Alanine aminotransferase increased | 1 participants |
| Cohort 3: Mavacamten 15 mg | Clinical Laboratory Tests Data | Neutrophil count increased | 1 participants |
| Cohort 3: Mavacamten 15 mg | Clinical Laboratory Tests Data | Neutrophil count decreased | 0 participants |
| Cohort 3: Mavacamten 15 mg | Clinical Laboratory Tests Data | Eosinophil percentage increased | 1 participants |
| Cohort 3: Mavacamten 15 mg | Clinical Laboratory Tests Data | Eosinophil count increased | 1 participants |
| Cohort 3: Mavacamten 15 mg | Clinical Laboratory Tests Data | Urobilinogen urine increased | 0 participants |
| Cohort 3: Mavacamten 15 mg | Clinical Laboratory Tests Data | White blood cell count increased | 0 participants |
| Cohort 4: Mavacamten 15 mg | Clinical Laboratory Tests Data | Neutrophil count decreased | 1 participants |
| Cohort 4: Mavacamten 15 mg | Clinical Laboratory Tests Data | Blood fibrinogen increased | 1 participants |
| Cohort 4: Mavacamten 15 mg | Clinical Laboratory Tests Data | Urobilinogen urine increased | 1 participants |
| Cohort 4: Mavacamten 15 mg | Clinical Laboratory Tests Data | Neutrophil count increased | 0 participants |
| Cohort 4: Mavacamten 15 mg | Clinical Laboratory Tests Data | Alanine aminotransferase increased | 0 participants |
| Cohort 4: Mavacamten 15 mg | Clinical Laboratory Tests Data | Hemoglobin decreased | 1 participants |
| Cohort 4: Mavacamten 15 mg | Clinical Laboratory Tests Data | White blood cell count increased | 0 participants |
| Cohort 4: Mavacamten 15 mg | Clinical Laboratory Tests Data | White blood cell count decreased | 1 participants |
| Cohort 4: Mavacamten 15 mg | Clinical Laboratory Tests Data | Eosinophil count increased | 0 participants |
| Cohort 4: Mavacamten 15 mg | Clinical Laboratory Tests Data | Eosinophil percentage increased | 0 participants |
Secondary
Heart Rate at Baseline and Day 75
Safety assessments will be performed by electrocardiogram (ECG) parameters findings during the whole study at specified time points
Time frame: Up to 75 days
Population: All 44 subjects included in the safety analysis set: cohort 1 12 subjects, cohort 2 12 subjects, cohort 3 12 subjects, cohort 4 8 subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Mavacamten 15 mg | Heart Rate at Baseline and Day 75 | Heart Rate-Baseline | 63.3 beats/min | Standard Deviation 8.7 |
| Cohort 1: Mavacamten 15 mg | Heart Rate at Baseline and Day 75 | Heart Rate-D75 | 64.8 beats/min | Standard Deviation 7.12 |
| Cohort 2: Mavacamten 25 mg | Heart Rate at Baseline and Day 75 | Heart Rate-D75 | 66.4 beats/min | Standard Deviation 7.88 |
| Cohort 2: Mavacamten 25 mg | Heart Rate at Baseline and Day 75 | Heart Rate-Baseline | 63.0 beats/min | Standard Deviation 10.44 |
| Cohort 3: Mavacamten 15 mg | Heart Rate at Baseline and Day 75 | Heart Rate-Baseline | 63.3 beats/min | Standard Deviation 10.44 |
| Cohort 3: Mavacamten 15 mg | Heart Rate at Baseline and Day 75 | Heart Rate-D75 | 67.5 beats/min | Standard Deviation 5.35 |
| Cohort 4: Mavacamten 15 mg | Heart Rate at Baseline and Day 75 | Heart Rate-Baseline | 62.8 beats/min | Standard Deviation 9.27 |
| Cohort 4: Mavacamten 15 mg | Heart Rate at Baseline and Day 75 | Heart Rate-D75 | 66.8 beats/min | Standard Deviation 7.17 |
Secondary
Number of Participants With Adverse Events
Safety assessments will be performed by incidence of adverse events during the whole study at specified time points
Time frame: Up to 75 days
Population: All 44 subjects included in the safety analysis set: cohort 1 12 subjects, cohort 2 12 subjects, cohort 3 12 subjects, cohort 4 8 subjects.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: Mavacamten 15 mg | Number of Participants With Adverse Events | Worst severity of TEAE(Mild) | 3 Participants |
| Cohort 1: Mavacamten 15 mg | Number of Participants With Adverse Events | TEAE leading to death | 0 Participants |
| Cohort 1: Mavacamten 15 mg | Number of Participants With Adverse Events | TESAE | 0 Participants |
| Cohort 1: Mavacamten 15 mg | Number of Participants With Adverse Events | Worst severity of TEAE(Moderate) | 0 Participants |
| Cohort 1: Mavacamten 15 mg | Number of Participants With Adverse Events | TEAE leading to study discontinuation | 0 Participants |
| Cohort 1: Mavacamten 15 mg | Number of Participants With Adverse Events | AESI | 0 Participants |
| Cohort 1: Mavacamten 15 mg | Number of Participants With Adverse Events | Number of subjects with at least 1 AE | 3 Participants |
| Cohort 1: Mavacamten 15 mg | Number of Participants With Adverse Events | Worst severity of TEAE(Severe) | 0 Participants |
| Cohort 1: Mavacamten 15 mg | Number of Participants With Adverse Events | Drug-related TEAEs | 0 Participants |
| Cohort 1: Mavacamten 15 mg | Number of Participants With Adverse Events | Number of subjects with at least 1 TEAE | 3 Participants |
| Cohort 2: Mavacamten 25 mg | Number of Participants With Adverse Events | AESI | 0 Participants |
| Cohort 2: Mavacamten 25 mg | Number of Participants With Adverse Events | Drug-related TEAEs | 1 Participants |
| Cohort 2: Mavacamten 25 mg | Number of Participants With Adverse Events | TEAE leading to death | 0 Participants |
| Cohort 2: Mavacamten 25 mg | Number of Participants With Adverse Events | TESAE | 0 Participants |
| Cohort 2: Mavacamten 25 mg | Number of Participants With Adverse Events | Number of subjects with at least 1 TEAE | 6 Participants |
| Cohort 2: Mavacamten 25 mg | Number of Participants With Adverse Events | TEAE leading to study discontinuation | 0 Participants |
| Cohort 2: Mavacamten 25 mg | Number of Participants With Adverse Events | Worst severity of TEAE(Mild) | 6 Participants |
| Cohort 2: Mavacamten 25 mg | Number of Participants With Adverse Events | Number of subjects with at least 1 AE | 6 Participants |
| Cohort 2: Mavacamten 25 mg | Number of Participants With Adverse Events | Worst severity of TEAE(Moderate) | 0 Participants |
| Cohort 2: Mavacamten 25 mg | Number of Participants With Adverse Events | Worst severity of TEAE(Severe) | 0 Participants |
| Cohort 3: Mavacamten 15 mg | Number of Participants With Adverse Events | Worst severity of TEAE(Moderate) | 1 Participants |
| Cohort 3: Mavacamten 15 mg | Number of Participants With Adverse Events | Number of subjects with at least 1 TEAE | 9 Participants |
| Cohort 3: Mavacamten 15 mg | Number of Participants With Adverse Events | TEAE leading to death | 0 Participants |
| Cohort 3: Mavacamten 15 mg | Number of Participants With Adverse Events | AESI | 0 Participants |
| Cohort 3: Mavacamten 15 mg | Number of Participants With Adverse Events | Worst severity of TEAE(Mild) | 8 Participants |
| Cohort 3: Mavacamten 15 mg | Number of Participants With Adverse Events | Number of subjects with at least 1 AE | 9 Participants |
| Cohort 3: Mavacamten 15 mg | Number of Participants With Adverse Events | TEAE leading to study discontinuation | 0 Participants |
| Cohort 3: Mavacamten 15 mg | Number of Participants With Adverse Events | Worst severity of TEAE(Severe) | 0 Participants |
| Cohort 3: Mavacamten 15 mg | Number of Participants With Adverse Events | Drug-related TEAEs | 0 Participants |
| Cohort 3: Mavacamten 15 mg | Number of Participants With Adverse Events | TESAE | 0 Participants |
| Cohort 4: Mavacamten 15 mg | Number of Participants With Adverse Events | AESI | 0 Participants |
| Cohort 4: Mavacamten 15 mg | Number of Participants With Adverse Events | Number of subjects with at least 1 AE | 3 Participants |
| Cohort 4: Mavacamten 15 mg | Number of Participants With Adverse Events | Number of subjects with at least 1 TEAE | 3 Participants |
| Cohort 4: Mavacamten 15 mg | Number of Participants With Adverse Events | Worst severity of TEAE(Mild) | 3 Participants |
| Cohort 4: Mavacamten 15 mg | Number of Participants With Adverse Events | Worst severity of TEAE(Moderate) | 0 Participants |
| Cohort 4: Mavacamten 15 mg | Number of Participants With Adverse Events | Worst severity of TEAE(Severe) | 0 Participants |
| Cohort 4: Mavacamten 15 mg | Number of Participants With Adverse Events | TESAE | 0 Participants |
| Cohort 4: Mavacamten 15 mg | Number of Participants With Adverse Events | TEAE leading to study discontinuation | 0 Participants |
| Cohort 4: Mavacamten 15 mg | Number of Participants With Adverse Events | TEAE leading to death | 0 Participants |
| Cohort 4: Mavacamten 15 mg | Number of Participants With Adverse Events | Drug-related TEAEs | 1 Participants |
Secondary
Physical Examination Findings
Safety assessments will be performed by physical examination findings during the whole study at specified time points
Time frame: Up to 75 days
Population: All 44 subjects included in the safety analysis set: cohort 1 12 subjects, cohort 2 12 subjects, cohort 3 12 subjects, cohort 4 8 subjects.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Mavacamten 15 mg | Physical Examination Findings | Number of abnormal but not clinically significant comprehensive physical examinations in baseline | 5 participants |
| Cohort 1: Mavacamten 15 mg | Physical Examination Findings | The number of abnormal with clinically significant comprehensive physical examinations in Day 75 | 0 participants |
| Cohort 1: Mavacamten 15 mg | Physical Examination Findings | Number of abnormal but not clinically significant comprehensive physical examinations in Day 75 | 5 participants |
| Cohort 2: Mavacamten 25 mg | Physical Examination Findings | Number of abnormal but not clinically significant comprehensive physical examinations in baseline | 2 participants |
| Cohort 2: Mavacamten 25 mg | Physical Examination Findings | The number of abnormal with clinically significant comprehensive physical examinations in Day 75 | 1 participants |
| Cohort 2: Mavacamten 25 mg | Physical Examination Findings | Number of abnormal but not clinically significant comprehensive physical examinations in Day 75 | 2 participants |
| Cohort 3: Mavacamten 15 mg | Physical Examination Findings | Number of abnormal but not clinically significant comprehensive physical examinations in Day 75 | 4 participants |
| Cohort 3: Mavacamten 15 mg | Physical Examination Findings | Number of abnormal but not clinically significant comprehensive physical examinations in baseline | 4 participants |
| Cohort 3: Mavacamten 15 mg | Physical Examination Findings | The number of abnormal with clinically significant comprehensive physical examinations in Day 75 | 0 participants |
| Cohort 4: Mavacamten 15 mg | Physical Examination Findings | Number of abnormal but not clinically significant comprehensive physical examinations in baseline | 2 participants |
| Cohort 4: Mavacamten 15 mg | Physical Examination Findings | The number of abnormal with clinically significant comprehensive physical examinations in Day 75 | 0 participants |
| Cohort 4: Mavacamten 15 mg | Physical Examination Findings | Number of abnormal but not clinically significant comprehensive physical examinations in Day 75 | 2 participants |