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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.
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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: Mavacamten 15 mg | Experimental | Cohort 1: 15 mg capsules × 1 on Day 1 |
|
| Cohort 2: Mavacamten 25 mg | Experimental | Cohort 2: 10 mg capsules x 1 and 15 mg capsules x 1 on Day 1 |
|
| Cohort 3: Mavacamten 15 mg | Experimental | Cohort 3: 15 mg capsules × 1 on Day 1 |
|
| Cohort 4: Mavacamten 15 mg | Experimental | Cohort 4: 15 mg capsules × 1 on Day 1 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mavacamten | Drug | Single fasted oral dose of Mavacamten 15/25 mg on Day 1 |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events | Safety assessments will be performed by incidence of adverse events during the whole study at specified time points | Up to 75 days |
| Body Weight at Screening and EOS |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jing Zhang, Doctor | Huashan Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Huashan Hospital Fudan University | Shanghai | Shanghai Municipality | 200040 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39014868 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| FG002 | 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 |
| FG003 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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) | 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. | Posted | Geometric Mean | Standard Deviation | h*ng/mL | Predose, Day 1, Day 7, Day 10, Day 14, Day 21, Day 28, Day 35, Day 45, Day 67 and Day 75 post-dose |
|
The study took about 80 days to monitor the adverse event for each subject.
Consistent with clinicaltrials.gov definitions.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
There are no special limitations and caveats to this trial.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Brianna Sun | Shanghai LianBio Development Co., Ltd | +862123081188 | brianna.sun@lianbio.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Apr 30, 2021 | Nov 28, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 28, 2022 | Nov 28, 2023 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D002312 | Cardiomyopathy, Hypertrophic |
| ID | Term |
|---|---|
| D009202 | Cardiomyopathies |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001020 | Aortic Stenosis, Subvalvular |
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| ID | Term |
|---|---|
| C000605992 | MYK-461 |
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|
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.
| Body weight (kg) will be measured at screening (baseline) and EOS(75 days). |
| Physical Examination Findings | Safety assessments will be performed by physical examination findings during the whole study at specified time points | Up to 75 days |
| 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 | Up to 75 days |
| 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 | Up to 75 days |
| BG002 | 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 |
| BG003 | 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 |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body mass index | Mean | Standard Deviation | kg/m^2 |
|
| CYP2C19 genotype | Count of Participants | Participants |
|
| Left ventricular ejection fraction(%) | Mean | Standard Deviation | % |
|
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 |
| OG002 | 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 |
| OG003 | 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 |
|
|
| Primary | Maximum Concentration (Cmax) | Determination of pharmacokinetics parameters as measured by maximum concentration (Cmax) | 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. | Posted | Geometric Mean | Standard Deviation | ng/mL | Predose, Day 1, Day 7, Day 10, Day 14, Day 21, Day 28, Day 35, Day 45, Day 67 and Day 75 post-dose |
|
|
|
| Primary | Time to Maximum Concentration (Tmax) | Determination of pharmacokinetics parameters as measured by time to maximum concentration (Tmax) | 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. | Posted | Median | Full Range | h | Predose, Day 1, Day 7, Day 10, Day 14, Day 21, Day 28, Day 35, Day 45, Day 67 and Day 75 post-dose |
|
|
|
| Primary | Elimination Half-life (T1⁄2) | Determination of pharmacokinetics parameters as measured by elimination half-life (T1⁄2) | 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. | Posted | Geometric Mean | Standard Deviation | h | Predose, Day 1, Day 7, Day 10, Day 14, Day 21, Day 28, Day 35, Day 45, Day 67 and Day 75 post-dose |
|
|
|
| Primary | Apparent Volume of Distribution (Vd/F) | Determination of pharmacokinetics parameters as measured by apparent volume of distribution (Vd/F) | 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. | Posted | Geometric Mean | Standard Deviation | mL | Predose, Day 1, Day 7, Day 10, Day 14, Day 21, Day 28, Day 35, Day 45, Day 67 and Day 75 post-dose |
|
|
|
| Primary | Apparent Clearance (CL/F) | Determination of pharmacokinetics parameters as measured by apparent clearance (CL/F) | 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. | Posted | Geometric Mean | Standard Deviation | mL/h | 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 | Number of Participants With Adverse Events | Safety assessments will be performed by incidence of adverse events during the whole study at specified time points | 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. | Posted | Count of Participants | Participants | Up to 75 days |
|
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | kg | Body weight (kg) will be measured at screening (baseline) and EOS(75 days). |
|
|
|
| Secondary | Physical Examination Findings | Safety assessments will be performed by physical examination findings during the whole study at specified time points | 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. | Posted | Number | participants | Up to 75 days |
|
|
|
| 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 | 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. | Posted | Mean | Standard Deviation | beats/min | Up to 75 days |
|
|
|
| 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 | 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. | Posted | Number | participants | Up to 75 days |
|
|
|
| 0 |
| 12 |
| 0 |
| 12 |
| 3 |
| 12 |
| EG001 | 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 | 0 | 12 | 0 | 12 | 6 | 12 |
| EG002 | 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 | 0 | 12 | 0 | 12 | 9 | 12 |
| EG003 | 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 | 0 | 8 | 0 | 8 | 3 | 8 |
| Oral herpes | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
|
| Appendicitis | Infections and infestations | MedDRA (24.1) | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA (24.1) | Systematic Assessment |
|
| Malaise | General disorders | MedDRA (24.1) | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (24.1) | Systematic Assessment |
|
| Conjunctival hyperaemia | Eye disorders | MedDRA (24.1) | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA (24.1) | Systematic Assessment |
|
| Haematochezia | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (24.1) | Systematic Assessment |
|
| Blood fibrinogen increased | Investigations | MedDRA (24.1) | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA (24.1) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (24.1) | Systematic Assessment |
|
| Neutrophil count increased | Investigations | MedDRA (24.1) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA (24.1) | Systematic Assessment |
|
| Eosinophil percentage increased | Investigations | MedDRA (24.1) | Systematic Assessment |
|
| Eosinophil count increased | Investigations | MedDRA (24.1) | Systematic Assessment |
|
| Urobilinogen urine increased | Investigations | MedDRA (24.1) | Systematic Assessment |
|
| White blood cell count increased | Investigations | MedDRA (24.1) | Systematic Assessment |
|
| Hemoglobin decreased | Investigations | MedDRA (24.1) | Systematic Assessment |
|
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| D001024 |
| Aortic Valve Stenosis |
| D000082862 | Aortic Valve Disease |
| D006349 | Heart Valve Diseases |
| Number of subjects with at least 1 TEAE |
|
| Worst severity of TEAE(Mild) |
|
| Worst severity of TEAE(Moderate) |
|
| Worst severity of TEAE(Severe) |
|
| Drug-related TEAEs |
|
| TESAE |
|
| TEAE leading to study discontinuation |
|
| TEAE leading to death |
|
| AESI |
|
| Baseline |
|
| Day 75 |
|
| Number of abnormal but not clinically significant comprehensive physical examinations in Day 75 |
|
| The number of abnormal with clinically significant comprehensive physical examinations in Day 75 |
|
| Heart Rate-D75 |
|
| White blood cell count decreased |
|
| Alanine aminotransferase increased |
|
| Neutrophil count increased |
|
| Neutrophil count decreased |
|
| Eosinophil percentage increased |
|
| Eosinophil count increased |
|
| Urobilinogen urine increased |
|
| White blood cell count increased |
|
| Hemoglobin decreased |
|