Conditions: Hypertrophic Cardiomyopathy
Keywords: Mavacamten
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 45
Healthy volunteers: yes

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)

Arms:
arm 1: Cohort 1: 15 mg capsules × 1 on Day 1 arm 2: Cohort 2: 10 mg capsules x 1 and 15 mg capsules x 1 on Day 1 arm 3: Cohort 3: 15 mg capsules × 1 on Day 1 arm 4: Cohort 4: 15 mg capsules × 1 on Day 1

Interventions: intervention 1: Mavacamten
Intervention descriptions: intervention 1: Single fasted oral dose of Mavacamten 15/25 mg on Day 1

Protocol document:
Prot_000.pdf: 
 
 
Clinical Study Protocol 
 
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 
 
Investigational Drug 
Mavacamten Capsules 
Protocol No. 
LB2001-101 
Phase of 
Development 
1 
Registration 
Category 
Chemical Drug Category 1 
Proposed Indication 
Obstructive Hypertrophic Cardiomyopathy 
Version and Date 
1.0/ 30 Apr 2021 
Sponsor 
Shanghai LianBio Development Co., Ltd. 
Address 
3rd floor, Building# 1, No. 400, Fang Chun Road, Shanghai Free Trade Zone, 
Shanghai, China 
 
 
Statement of Confidentiality 
Ownership of the information contained herein belongs to Shanghai LianBio Development Co., 
Ltd. Confidential information is provided herein in accordance with the agreed and signed 
Disclosure and Nondisclosure Agreement. Without a prior written authorization, this document 
or its copy or any information contained herein cannot be disclosed to any third party (except 
those who conform to the Disclosure and Nondisclosure Agreement and coordinate the conduct 
of research work in the organization). 
 


Protocol No.: LB2001-101 
CONFIDENTIAL 
V1.0/30 Apr 2021 
 
Page 1 
Version History 
 
Version Number 
Version Date 
Major Amendments and Reason 
 
 
 
 
 
 


Protocol No.: LB2001-101 
CONFIDENTIAL 
V1.0/30 Apr 2021 
 
Page 1 
Synopsis 
Title 
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 
Protocol No. 
LB2001-101 
Sponsor 
Shanghai LianBio Development Co., Ltd. 
Phase of 
Development 
1 
Registration 
Category 
Chemical Drug Category 1 
Proposed 
Indication 
Obstructive Hypertrophic Cardiomyopathy (oHCM) 
Investigational 
Drug 
Name: Mavacamten Capsules 
Strength: 10 mg and 15 mg 
Dosage form: capsules 
Storage condition: 2°C to 25°C (36°F to 
77°F)  
Objectives 
Primary: 
• 
To evaluate the pharmacokinetics (PK) of a single oral dose of mavacamten in 
healthy adult Chinese subjects with different CYP2C19 genotypes. 
Secondary: 
• 
To evaluate the safety and tolerability of a single oral dose of mavacamten in 
healthy adult Chinese subjects with different CYP2C19 genotypes. 
Exploratory: 
• 
To evaluate the population PK. 
PK Endpoints 
PK endpoints include: 
• 
Area under the curve (AUC) (0-last), AUC(0-inf); 
• 
Maximum concentration (Cmax); 
• 
Time to maximum concentration (Tmax); 
• 
Elimination half-life (T1⁄2); 
• 
Apparent volume of distribution (Vd/F); 
• 
Apparent clearance (CL/F). 
Safety 
Endpoints 
Safety endpoints include: 
• 
Vital signs; 
• 
Physical examination findings; 
• 
Electrocardiogram (ECG) parameters; 
• 
Clinical laboratory tests data, including hematology and blood chemistry, 
coagulation and urinalysis parameters; 
• 
Adverse events (AEs). 
Exploratory 
Endpoint 
• 
Population PK model may be assessed to investigate ethnic differences on key PK 
parameters including clearance and volume of distribution. 
Sample Size 
Approximately 44 healthy adult Chinese subjects are expected to be enrolled in this 
study according to CYP2C19 genotypes into 4 cohorts. 
• 
Cohort 1 and Cohort 2 (n = 12): ultra-rapid metabolizer (UM), rapid metabolizer 
(RM), or normal metabolizer (NM) of cytochrome P450 (CYP) 2C19 to ensure 


Protocol No.: LB2001-101 
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V1.0/30 Apr 2021 
 
Page 2 
that data will be obtained for at least 10 subjects; 
• 
Cohort 3 (n = 12): intermediate metabolizer (IM) of CYP2C19 to ensure that data 
will be obtained for at least 10 subjects; 
• 
Cohort 4 (n = 8): poor metabolizer (PM) of CYP2C19 to ensure that data will be 
obtained for at least 6 subjects. 
Study Design 
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 oral dose of mavacamten to evaluate its PK 
profile. 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. 
 
Inclusion 
Criteria 
Subjects can be enrolled in the study if they meet all of the following criteria: 
1. 
Male or female between the ages of 18 and 60 (inclusive) at screening (one sex 
not less than 25% each cohort); 
2. 
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;  
3. 
With a body mass index (BMI) between 18 kg/m2 and 30 kg/m2 (inclusive) at 
screening; 
4. 
With a resting left ventricular ejection fraction (LVEF) ≥ 55% by 
echocardiography at screening; 
5. 
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; 
6. 
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): 


Protocol No.: LB2001-101 
CONFIDENTIAL 
V1.0/30 Apr 2021 
 
Page 3 
• 
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; 
• 
Intrauterine device (IUD); 
• 
Intrauterine system (IUS); 
• 
Bilateral tubal ligation; 
• 
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; 
7. 
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; 
8. 
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 
Subjects must not be enrolled in the study if they meet any of the following criteria: 
1. 
History of clinically significant arrhythmia, left ventricular (LV) systolic 
dysfunction, or coronary artery disease, or QTc >450 ms at screening and on Day 
-1; 
2. 
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; 
3. 
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; 
4. 
Vital sign meet any of the following criteria: a) ear temperature was greater than 
37.5 ℃; b) heart rate was greater than 100 beats / min or less than 50 beats / min; 
c) systolic blood pressure was greater than 139 mmHg or less than 90 mmHg; d) 
diastolic blood pressure was greater than 90 mmHg or less than 50 mmHg at 
screening and on Day -1; 
5. 
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); 
6. 
History or evidence of any other clinically significant abnormalities, conditions, 
or diseases (with the exception of those outlined above) 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; 
7. 
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;  
8. 
Positive test for alcohol or drug abuse at screening and on Day -1; 
9. 
Use of tobacco exceeding 10 cigarettes per day or nicotine-containing products 


Protocol No.: LB2001-101 
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V1.0/30 Apr 2021 
 
Page 4 
of equivalent amount within 28 days prior to screening; 
10. 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); 
11. Prior exposure to mavacamten; 
12. 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; 
13. Unable to comply with the study restrictions/requirements, including the number 
of required visits to the clinical site; 
14. Had donated over or lost 400 mL blood in 60 days or plasma in the last 2 weeks 
prior to the screening visit; 
15. Infection of coronavirus disease 2019 (COVID-19) (i.e., positive for polymerase 
chain reaction) within 6 months prior to screening; 
16. Unsuitable to participate in the study as judged by the investigator. 
Study 
Procedures 
This study will consist of the following 5 periods: 
• 
Pre-screening period (Day -43 to Day -15, up to 28 days) 
Subjects who sign the pre-screening informed consent form (ICF) will enter the pre-
screening period to determine their CYP2C19 genotypes. 
• 
Screening period (Day-14 to Day -2, up to 13 days): 
After determining their genotypes, subjects who sign the main ICF will enter the 
screening period to complete screening examinations. 
• 
In-house period (Day -1 to Day 3, total 4 days): 
Eligible subjects will be divided into 4 parallel cohorts based on their CYP2C19 
genotypes (Cohort 1 and Cohort 2: CYP2C19 UM, RM, or NM; Cohort 3: CYP2C19 
IM; Cohort 4: CYP2C19 PM). 
Subjects will be admitted to the clinical research unit (CRU) the day before dosing 
(Day -1), and receive a single oral dose of mavacamten on Day 1 (Cohort 1: 15 mg; 
Cohort 2: 15 mg; Cohort 3: 15 mg; Cohort 4: 15 mg). They will remain in the CRU 
until Day 3 (48 hours after administration of mavacamten) for PK and safety 
assessments. 
• 
Outpatient period (Day 4 to Day 75, total 72 days): 
Subjects who have finished the examinations on Day 3 will enter the outpatient period. 
Outpatient visits will occur on Days 7, 10, 14, 21, 28, 35, 45 and 60 to collect blood 
samples and perform safety assessments. 
• 
End of study visit (Day 75) 
End of study (EOS) Visit will occur on Day 75 to complete the final safety examination 
and obtain the last blood samples for PK assessment. 
Dosing 
Regimen and 
Routes of 
Administratio
n 
• 
Dosing Regimen 
Subjects will receive a single dose of mavacamten on Day 1. 
Cohort 1: 15 mg (15 mg capsules × 1); 
Cohort 2: 25 mg (10 mg capsules x 1 and 15 mg capsules x 1); 
Cohort 3: 15 mg (15 mg capsules × 1); 
Cohort 4: 15 mg (15 mg capsules × 1); 
• 
Route of Administration 
The drug is to be administered orally. Subjects should fast overnight (for at least 8 
hours) before taking mavacamten with 240 mL water, and should not eat any food until 
3 hours after dosing. Water will be allowed except for 1 hour before and after dosing. 


Protocol No.: LB2001-101 
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V1.0/30 Apr 2021 
 
Page 5 
PK Sampling 
• 
PK Sampling Schedule 
3 mL whole blood will be collected at each of the following time points for PK analysis: 
pre-dose (within 60 min before dosing), 10 min, 20 min, 30 min, 45 min, 1 h, 1.5 h, 2 
h, 3 h, 4 h, 8 h, 12 h, 24 h and 48 h, and on Days 7, 10, 14, 21, 28, 35, 45, 60 and 75 
after dosing of mavacamten. 
Statistical 
Methods 
Approximately 44 subjects will be enrolled in this study. 
⚫ 
Datasets 
➢ 
Pharmacokinetic Set (PKS): 
All subjects exposed to mavacamten and with at least one plasma concentration will 
be included in the PKS. 
➢ 
Safety Analysis Set (SAS): 
All subjects exposed to mavacamten, regardless of the doses administered, will be 
included in the SAS. 
⚫ 
Statistical Analysis 
➢ 
PK Analyses: 
Individual plasma concentration-time data of mavacamten will be displayed and 
summarized graphically on the linear and semi-log scales. PK parameters, including 
AUC(0-last), AUC(0-inf), Cmax, Tmax, T1/2, Vd/F, CL/F will be calculated using a non-
compartmental model. 
The concentration-time data for each cohort will be summarized and the mean 
concentration-time curve will be plotted on the linear and semi-log scales by cohort. 
Descriptive statistical analysis for parameters will be performed by cohort. 
Statistics include the number of subjects, arithmetic mean, geometric mean (GM), 
standard deviation (SD), and coefficient of variation (CV), minimum (min), median, 
and maximum (max). 
➢ 
Safety Analyses: 
Safety analyses will be based on descriptive statistics (summary tables) as well as 
individual data for AEs, clinical laboratory values, vital signs, and ECG parameters. 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). 
AEs will be monitored throughout the study to determine their severity and their 
potential relationship to the investigational drug. 
The number of subjects who experience AEs after dosing (from single dose 
administration to the EOS) will be summarized by cohort. 
➢ 
Population PK (PopPK) Analysis: 
PopPK analysis will be conducted with the pooled data from the current study LB2001-
101 and other mavacamten studies. Additional details on PopPK model development 
and analysis will be provided in a separate PopPK data analysis plan (DAP), and the 
results of PopPK analysis will be reported in a separate clinical study report (CSR). 
Note: PopPK analysis will be performed only after approval by relevant regulatory 
authorities and within the approved scope. 


Protocol No.: LB2001-101 
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V1.0/30 Apr 2021 
 
Page 6 
Table 1 Study Flow Chart 
Weeks 
Pre-screening 
Screening 
Period 
In-house Period 
Outpatient Period 
End of 
study 
visit 
Days 
D-43 to D-15 
D-14 to 
D-2 
D-1 
D1 
D2 
D3 
D7 
D10 
D14 
D21 
D28 
D35 
D45 
D60 
D75 
Visit Window (day) 
 
 
 
 
 
 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
Signing the pre-screening ICF1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CYP2C19 genotyping 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signing the main ICF 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Assign subject number 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs3 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination4 
 
X 
X 
 
 
X 
 
 
 
 
 
 
 
 
X 
Weight, height5 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
12-lead ECG6 
 
X 
X 
X 
 
X 
 
 
 
 
X 
 
 
X 
X 
Echocardiography 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology7 
 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
X 
Blood chemistry8 
 
X 
X 
 
 
X 
 
 
 
 
X 
 
 
 
X 
Urinalysis9 
 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
X 
Coagulation10 
 
X 
X 
 
 
X 
 
 
 
 
X 
 
 
 
X 
FSH11 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test12 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Urine Pregnancy test12 
 
 
X 
 
 
 
 
 
 
 
X 
 
 
X 
 
Hepatitis B, C, and HIV virology 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Alcohol or drug abuse test13 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Investigational drug14 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
PK blood sampling15 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AE16 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Abbreviations: AE = adverse event; ALP = alkaline phosphatase; ALT = alanine aminotransferase; APTT = activated partial thromboplastin time; AST = aspartate 


Protocol No.: LB2001-101 
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V1.0/30 Apr 2021 
 
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aminotransferase; BP = blood pressure; CK = creatine kinase; CYP = cytochrome P450; ECG = electrocardiogram; EOS = end of study; FIB = fibrinogen; FSH = 
follicle stimulating hormone; HIV = human immunodeficiency virus; HR = heart rate; ICF = informed consent form; INR = international normalized ratio; PK = 
pharmacokinetic; PT = prothrombin time; QD = once daily; RBC = red blood cell; SAE = serious AE; TT = thrombin time; WBC = white blood cell. 
Note: safety laboratory tests (hematology, blood chemistry, coagulation, urinalysis) are not required to be repeated on Day -1 if the latest results are within 7 days 
from Day -1. 12-lead ECG test is not required to be repeated on Day -1 if the latest result is within 3 days from Day -1. 
1. Signing the pre-screening ICF: after signing of the pre-screening ICF, test for determining CYP2C19 genotypes could be performed. 
2. Demographics: including age, gender and ethnicity. 
3. Vital signs: including temperature, heart rate, respiratory rate, and systolic and diastolic BP in a supine position after 5 minutes of rest. While the subject is in the 
CRU, vital signs will be taken upon rising in the morning. On Day 1, vital signs should be collected before IMP dosing. 
4. Physical examination: a complete physical examination will be conducted at screening and the EOS Visit, while abbreviated physical examinations on other visits.  
A complete physical examination includes assessments of general appearance, skin, head and neck, mouth, lymph nodes, thyroid, abdomen, and musculoskeletal, 
cardiovascular, neurological, and respiratory systems. Brief physical examination included cardiovascular and respiratory examinations. 
5. Height, weight: weight (kg) will be measured at screening and the EOS Visit. And height (cm) will be measured at screening. 
6. 12-lead ECG: it will be performed after 10 minutes of rest at screening, on Day -1, Day 1 (pre-dose: within 3h before dosing, and post-dose: 2 h±30min after dosing ), 
Day 3, Day 28, Day 60, and at the EOS Visit. When the 12-lead ECG is completed, a 10-second paper ECG will be obtained as the subject’s source documentation. If 
clinical symptoms or clinical indications occur accordingly, the investigator may consider increasing the frequency of test. 
7. Hematology: including hematocrit, hemoglobin, RBC count, WBC count and differential, platelet count. 
8. Blood chemistry: including albumin, total protein, direct bilirubin, total bilirubin, ALP, ALT, AST, creatinine, urea nitrogen, uric acid, CK, chlorine, potassium, 
sodium, calcium, magnesium, and glucose. 
9. Urinalysis: including urine glucose, urine ketone bodies, urine pH, urine protein, urine specific gravity, urine leukocyte esterase, urine WBC and urine RBC. 
10. Coagulation: including PT, INR, APTT, FIB, and TT. 
11. FSH: FSH test will be performed at screening for postmenopausal women to confirm their postmenopausal status (serum pregnancy test at screening). If the result 
of FSH test shows that the subject is not postmenopausal, a pregnancy test (serum or urine) is required to be performed at another visit to ensure that the subject is not 
pregnant. 
12. Pregnancy test: it will be performed in women of childbearing potential only. Serum pregnancy test will be performed at screening and the EOS Visit. Urine 
pregnancy test will be performed on Day -1, Day 28 and Day 60. 
13. Alcohol or drug abuse test: a combination drug detection kit (colloidal gold method) will be used for this test to detect the amount of morphine, ketamine, 
tetrahydrocannabinic acid, methamphetamine, 3,4-Methylenedioxymethamphetamine and cocaine in human urine. 
14. Investigational drug: administered orally on Day 1. 
15. PK blood sampling: blood samples will be obtained at pre-dose (within 60 min before dosing), 10 min, 20 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 8 h, 12 h, 
24 h and 48 h, and on Days 7, 10, 14, 21, 28, 35, 45, 60, and 75 after dosing of mavacamten to determine its plasma concentrations. 
16. AEs: during the pre-screening and screening period, only study procedure -related AEs (e.g., blood sampling) will be collected. 


Protocol No.: LB2001-101 
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V1.0/30 Apr 2021 
 
Page 8 
Table 2 PK Sampling Schedule 
 
In-house Period 
Outpatient Period 
End of 
study 
visit 
Days 
D 1 
D 2 
D 3 
D 7 
D 10 
D 14 
D 21 
D 28 
D 35 
D 45 
D 60 
D 75 
Visit 
Window 
(day) 
0 
0 
0 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
Collection 
time points 
Pre-dose (within 
60 min before 
dosing) 
24 h ± 1 h 
post-dose 
48 h ± 1 h 
post-dose 
Outpatient 
visits: 
144 h ± 24 
h post-dose 
on Day 1 
Outpatient 
visits: 
216 h ± 24 
h post-dose 
on Day 1 
Outpatient 
visits: 
312 h ± 24 
h post-dose 
on Day 1 
Outpatient 
visits: 
480 h ± 24 
h post-dose 
on Day 1 
Outpatient 
visits: 
648 h ± 24 
h post-dose 
on Day 1 
Outpatient 
visits: 
816 h ± 24 
h post-dose 
on Day 1 
Outpatient 
visits: 
1056 h ± 
24 h post-
dose on 
Day 1 
Outpatient 
visits: 
1416 h ± 
24 h post-
dose on 
Day 1 
 
EOS Visit: 
1776 h ± 
24 h post-
dose on 
Day 1 
10 min±2 min 
20 min±2 min 
30 min±2 min 
45 min±2 min 
1 h±2 min 
1.5 h±3 min 
2 h±3 min 
3 h±3 min 
4 h±3 min 
8 h±5 min 
12 h±5 min 
 


Protocol No.: LB2001-101 
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Page 9 
TABLE OF CONTENTS 
Clinical Study Protocol 
1 
Version History 
1 
Synopsis 
1 
TABLE OF CONTENTS 
9 
List of Tables 
13 
List of Appendices 
13 
List of Abbreviations 
14 
1. Introduction 
16 
1.1 Background 
16 
1.2 Overview of Mavacamten 
17 
1.2.1 Basic Information 
17 
1.2.2 Clinical Experience with Mavacamten 
17 
1.3 Known and Potential Benefits and Risks 
18 
2. Rationale for the Study and Administration 
21 
2.1 Rationale for the Study 
21 
2.2 Rationale for Dose Selection 
21 
3. Objectives 
22 
4. Overall Study Design 
23 
4.1 Study Design 
23 
4.2 Study Periods 
23 
4.3 Study Procedures 
24 
4.3.1 Pre-screening Period (Day -43 to Day -15, up to 28 days) 
24 
4.3.2 Screening Period (Day -14 to Day -2, up to 13 days) 
24 
4.3.3 In-house Period (Day -1 to Day 3) 
24 
4.3.4 Outpatient Period (Day 4 to Day 75) 
24 
4.3.5 End of Study visit (Day 75) 
24 
4.3.6 Unscheduled Visits 
24 
4.3.7 Missed Visits 
24 
4.4 Behavioral Restrictions on Subjects 
24 
5. Study Population 
26 
5.1 Study Population 
26 
5.2 Subject's Screening Number 
26 
5.3 Inclusion Criteria 
26 
5.4 Exclusion Criteria 
27 
5.5 Withdrawal & Replacement of Subjects and Termination of Clinical Trial 
28 
5.5.1 Withdrawal of Subjects from Clinical Trial 
28 
5.5.2 Subject Replacement 
30 


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Page 10 
5.5.3 Discontinuation of the Clinical Study 
30 
6. Investigational Drug 
31 
6.1 Basic Information of Mavacamten 
31 
6.2 Preparation, Handling, Storage, and Accountability 
31 
6.3 Dose Regimen 
31 
6.4 Administration 
32 
6.5 Dosing Compliance 
32 
6.6 Prior and Concomitant Therapy 
32 
6.6.1 Prior Therapy 
32 
6.6.2 Concomitant Medications 
32 
6.6.3 Prohibited Medications 
32 
7. Study Assessments 
33 
7.1 PK Assessments 
33 
7.2 Safety Assessments 
33 
8. Assessment, Recording and Reporting of Adverse Events 
35 
8.1 Definitions 
35 
8.1.1 Adverse Events 
35 
8.1.2 Serious Adverse Events (SAEs) 
36 
8.2 Collection and Reporting of AEs 
36 
8.2.1 Collection Time 
36 
8.2.2 Description 
36 
8.2.3 Start Date/Time and Stop Date/Time 
36 
8.2.4 Relationship to Study Drug 
36 
8.2.5 Intensity 
37 
8.2.6 Seriousness 
37 
8.2.7 Outcomes 
38 
8.3 Reporting and Assessment of SAE 
38 
8.4 Reporting of Adverse Events of Special Interest 
38 
8.5 Reporting of Drug-induced Liver Injury 
38 
8.6 Follow-up of AEs and SAEs 
38 
8.7 Reporting and Follow-up of Pregnancy 
38 
8.8 Safety Reporting to Investigators, Institutional Review Boards, Independent Ethics 
Committees, and Regulatory Authorities 
40 
9. Risks and Precautions 
41 
9.1 General Risks 
41 
9.2 Pregnancy 
41 
9.2.1 Avoidance of Pregnancy 
41 
9.2.2 Acceptable Methods of Contraception 
41 
9.2.3 Pregnancy Reporting and Follow-up 
41 
10. Statistical Methods 
42 
10.1 10.1 Sample Size 
42 
10.2 Study Endpoints 
42 


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10.2.1 Pharmacokinetic Endpoints 
42 
10.2.2 Safety Endpoints 
42 
10.2.3 Exploratory Endpoint 
42 
10.3 Statistical Analysis 
43 
10.3.1 Statistical Analysis Datasets 
43 
10.3.2 General Principles 
43 
10.3.3 Subject Disposition 
43 
10.3.4 Demographic and Baseline Characteristics 
43 
10.3.5 Efficacy Analysis 
43 
10.3.6 Pharmacokinetic Analysis 
43 
10.3.7 Ethnic Impact 
44 
10.3.8 Safety Analysis 
44 
10.3.9 PopPK Analysis 
44 
11. Data Collection and Management 
45 
11.1 Data Confidentiality 
45 
11.2 Study Site Monitoring 
45 
11.3 Data Collection 
46 
11.4 Database Management and Quality Control 
46 
11.5 Study Documentation, Record Keeping and Retention of Documents 
47 
12. Study Compliance and Ethical Considerations 
48 
12.1 Regulatory and Ethical Compliance 
48 
12.2 Informed Consent 
48 
12.3 Ethics Committee 
48 
12.4 Confidentiality of Study Documents and Subject Records 
49 
13. Management Procedures 
50 
13.1 Sponsor's Responsibilities 
50 
13.1.1 Subject Data Confidentiality 
50 
13.1.2 Investigator Training 
50 
13.1.3 Ongoing Communication of Safety Information During the Study 
51 
13.1.4 Study Monitoring 
51 
13.1.5 Study Auditing and Inspecting 
51 
13.2 Investigator's Responsibilities 
51 
13.2.1 Screening Log 
51 
13.2.2 Mavacamten Accountability 
51 
13.2.3 Reporting and Recording of Study Data 
52 
13.2.4 Source Data and Documents 
52 
13.2.5 Subject Identity Information 
53 
13.2.6 Record Retention 
53 
13.2.7 Protocol Deviations 
53 
13.2.8 Blood Sample Collection/Storage 
53 
13.3 Protocol Amendments and Study Administrative Instructions 
54 
13.4 Study Management 
54 
14. Publication Policy 
56 


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15. References 
57 
Appendix 1 Laboratory Tests 
59 
Sponsor’s Signature Page 
60 
Investigator's Signature Page 
61 
 


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List of Tables 
Table 1 Study Flow Chart ....................................................................................................... 6 
Table 2 PK Sampling Schedule ............................................................................................... 8 
Table 3 Summary of PK Parameters from Study MYK-461-011 and Study MYK-461-012
........................................................................................................................................... 18 
Table 4 Investigational Drug ................................................................................................. 31 
 
List of Appendices 
Appendix 1 Laboratory Tests ............................................................................................... 59 


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List of Abbreviations 
Abbreviations 
Definitions 
AE 
Adverse event 
AESI 
Adverse events of special interest 
AF 
Atrial fibrillation 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
APTT 
Activated partial thromboplastin time 
AUC 
Area under the curve 
BIL 
Bilirubin 
BMI 
Body mass index 
BP 
Blood pressure 
β-hCG 
Beta human chorionic gonadotropin 
cGMP 
Current Good Manufacturing Practice 
CDE 
Center for Drug Evaluation 
Cmax 
Maximum concentration 
CK 
Creatine kinase 
CL/F 
Apparent clearance 
CRU 
Clinical research unit 
COVID-19 
Coronavirus disease 2019 
CRO 
Contract research organization 
CSP 
Clinical study protocol 
CSR 
Clinical study report 
CV 
Cardiovascular 
CV 
Coefficient of variation 
CYP 
Cytochrome P450 
DAP 
Data analysis plan 
DSUR 
Development Safety Update Report 
EC 
Ethics committee; refers to an IRB or IEC or equivalent 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data collection 
EOS 
End of study 
ET 
Early termination 
FAS 
Full analysis set 
FIB 
Fibrinogen 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
GM 
Geometric mean 
HB 
Hemoglobin 
HBV 
Hepatitis B virus 
HBsAb 
hepatitis B surface antibody 
HCV 
Hepatitis C virus 
HCM 
Hypertrophic Cardiomyopathy 
HOCM 
Hypertrophic obstructive cardiomyopathy 
hERG 
Human ether-à-go-go-related gene 
HIV 
Human immunodeficiency virus 
HR 
Heart rate 
IB 
Investigator’s Brochure 
ICD 
Implantable cardioverter defibrillator 
ICF 
Informed Consent Form 


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Abbreviations 
Definitions 
ICH 
International Conference on Harmonization 
IEC 
Independent ethics committee 
IM 
Intermediate metabolizer 
IME 
Important medical events 
IMP 
Investigational medicinal product 
INR 
International normalized ratio 
IRB 
Institutional review board 
IUD 
Intrauterine device 
IUS 
Intrauterine system 
LV 
Left ventricle 
LVEF 
Left ventricular ejection fraction 
LVH 
Left ventricular hypertrophy 
LVOT 
Left ventricular outflow tract 
LVOTO 
Left ventricular outflow track obstruction 
MedDRA 
Medical Dictionary for Regulatory Activities 
MR 
Mitral regurgitation 
nHCM 
Non-obstructive hypertrophic cardiomyopathy 
NM 
Normal metabolizer 
NMPA 
National Medical Products Administration 
oHCM 
Obstructive Hypertrophic Cardiomyopathy 
pH 
Pondus hydrogenii 
PK 
Pharmacokinetics 
PKS 
Pharmacokinetics set 
PopPK 
Population pharmacokinetics 
PM 
Poor metabolizer 
PT 
Preferred term 
PT 
Prothrombin time 
PPS 
Per-Protocol set 
QD 
Once daily 
QTc  
Corrected QT interval 
QTcF 
QT Interval corrected by heart rate using Fridericia's formula 
RBC 
Red blood cell 
RM 
Rapid metabolizer 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SAS 
Safety analysis set 
SCD 
Sudden cardiac death 
SD 
Standard deviation 
SOC 
System Organ Class 
SRT 
Septal reduction therapy 
SS 
Safety analysis set 
SUSAR 
Suspected unexpected serious adverse reaction 
T1/2 
Elimination half-life 
TEAE 
Treatment-emergent adverse events 
TT 
Thrombin time 
Tmax 
Time to maximum concentration 
UM 
Ultra-rapid metabolizer 
ULN 
Upper limit of normal 
Vd/F 
Apparent volume of distribution 
WBC 
White blood cell 
 
 


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1. Introduction 
1.1 Background 
Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder defined by left 
ventricular (LV) hypertrophy that cannot be explained by other cardiac or systemic diseases. 
HCM is a chronic, progressive disease of the cardiomyocyte, and largely involves the cardiac 
sarcomere, with a diverse clinical presentation and course. Over time, HCM results in tissue 
remodeling characterized histologically by myocyte hypertrophy and disarray, microvascular 
remodeling, and fibrosis [1]. Approximately 40% of patients with sporadic HCM and 60% of 
those with a family history of HCM have a mutation in one or more sarcomeric structural genes 
[2-5]. Mutations in cardiac myosin and other sarcomeric proteins appear to increase net power 
generation by the sarcomere [6-8], consistent with the generally hypercontractile state and 
impaired compliance of the myocardium observed clinically in HCM. Recent estimates of the 
prevalence of HCM using information from large administrative databases indicate that the 
prevalence of clinically diagnosed HCM ranges from 3 to 7 per 10,000 [9 to 12]. It is estimated 
that there are around 1 million adults affected by HCM in China [13]. 
Two HCM phenotypes are recognized based on the peak left ventricular outflow tract (LVOT) 
gradient, namely obstructive hypertrophic cardiomyopathy (oHCM, also known as 
hypertrophic obstructive cardiomyopathy [HOCM]) and non-obstructive hypertrophic 
cardiomyopathy (nHCM), where obstruction is defined as a peak LVOT gradient ≥30 mmHg 
at rest or with provocation [3]. Approximately 70% of individuals diagnosed with HCM have 
oHCM [14]. Based on this, the prevalence rate of oHCM is likely between 2 and 5 per 10,000, 
based on the recent estimates of HCM. The precise mechanism of LVOT obstruction is 
unknown, but the combination of the abnormal ventricular geometry caused by septal 
hypertrophy, reduced ventricular cavity size, and the pathologic elongation of the mitral valve 
leaflets are considered as contributing factors [15]. Outflow tract obstruction can produce 
increased LV systolic pressure and an array of subsequent abnormalities, including 
prolongation of ventricular relaxation, elevation of LV diastolic pressure, mitral regurgitation 
(MR), atrial fibrillation (AF), myocardial ischemia, and decreased forward cardiac output [16]. 
The presence of LVOT obstruction is an important prognostic factor in HCM, and is associated 
with an increased risk of progressive disease, congestive heart failure, stroke, and death [17, 18]. 
The risk of sudden cardiac death (SCD), which is one of the most common non-traumatic 
causes of death in young adults and sometimes the first manifestation of HCM, is also increased 
in the presence of LVOT obstruction [3,19,20]. 
The current guideline-recommended drugs for HCM mainly depend on the empirical use of 
drugs for cardiovascular (CV) disease, including beta-blockers, verapamil, diltiazem, and 
disopyramide [3,2,2]. These drugs cannot alter the natural course of HCM and only have modest 
effect on peak LVOT gradient. In oHCM, septal reduction therapy (SRT) may reduce 
obstruction and improve LV outflow, and an implantable cardioverter-defibrillator (ICD) may 
prevent SCD, but both involve invasive procedures and require specialized operators and 
experienced clinical centers, and may not be applicable to all patients [23]. Cardiac transplant is 
the only option when pharmacologic options fail to adequately manage oHCM. None of these 
treatment options address the underlying etiology of HCM. Because of the huge unmet clinical 
need for the treatment of HCM, an urgent need for innovative drug development emerges. The 
Class 1 new drug of mavacamten to be evaluated in this trial boasts a breakthrough mechanism, 
and is being investigated in multiple clinical studies worldwide, showing good prospects for 
its clinical application in the treatment of HCM. Brief description will be made in the next 
section. 


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1.2 Overview of Mavacamten 
1.2.1 Basic Information 
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. The sponsor is developing mavacamten for the treatment of Chinese 
adults with symptomatic oHCM. 
1.2.2 Clinical Experience with Mavacamten 
To date, 18 clinical studies have been initiated to investigate the safety and tolerability of 
mavacamten. Please refer to the Investigator's Brochure (IB) for detailed information of these 
studies. The most relevant data to this study are the results from MYK-461-011 and MYK-
461-012, which are briefly described below: 
• 
Study MYK-461-011 
The MYK-461-011 study was a phase 1, single-center, prospective, open-label, parallel-group 
clinical study to evaluate the PK profile of mavacamten administered by a single oral dose to 
healthy Japanese and Caucasian subjects. The study enrolled 20 healthy Japanese subjects and 
8 healthy Caucasian subjects whose cytochrome P450 (CYP) 2C19 genotypes were ultra-rapid 
metabolizer (UM), rapid metabolizer (RM), normal metabolizer (NM) or intermediate 
metabolizer (IM). Three sequential cohorts (Cohort 1-3) of healthy Japanese subjects received 
a single dose of mavacamten ranging from 5 mg, 15 mg to 25 mg. To compare the PK profile 
between Japanese and Caucasian subjects, healthy Caucasian subjects (Cohort 4) received a 
single dose of 25 mg mavacamten. The results showed that mavacamten was rapidly absorbed 
with a median Tmax of 0.5 hours. The exposure of mavacamten was increased in an almost dose-
proportional manner between 5 and 15 mg. The geometric means (GM) of maximum 
concentration (Cmax), area under the curve (AUC)(0-last) and AUC(0-inf) in Japanese and Caucasian 
subjects were similar. The results of Caucasian subjects showed slightly higher variability. The 
Japanese and Caucasian subjects also showed similar mean elimination half-lifes (T1/2) of 
approximately 155 hours. The mean volume of distribution (Vd/F) and Vd,z/F were comparable 
between Japanese and Caucasian subjects. The results indicated no significant differences in 
the PK data between Japanese and Caucasian subjects. Therefore, dose modifications based on 
PK were not required for subjects of different ethnicities. 
There were no deaths, SAEs or AEs of moderate severity. All treatment-emergent adverse 
events (TEAEs) (n = 4) were mild in severity. One TEAE was considered as related to the 
investigational drug (headache in a Japanese subject who received 15 mg mavacamten). Other 
TEAEs were judged to be unrelated to the investigational drug (1 upper respiratory tract 
infection, 1 viral upper respiratory tract infection, and 1 hypoaesthesia). 
• 
Study MYK-461-012 
MYK-461-012 was a single-center, open-label, parallel-group, phase 1 clinical trial evaluating 
the PK profile of mavacamten administered by a single dose (15 mg) to 16 healthy Asian 
subjects (8 CYP2C19 NM, 8 CYP2C19 PM). 
Following a single dose of 15 mg mavacamten to subjects of CYP2C19 PM, the Cmax was 489.9 
ng/mL; median Tmax occurred at 0.75 hours post-dose, with a T1/2 of 552.8 hours; the AUC(0-
last) and AUC(0-inf) were 35,310 and 42,800 h·ng/mL, respectively; and the CL/F and Vz/F were 
350.5 mL/h and 279,500 mL, respectively. Overall exposure of mavacamten was higher in 
CYP2C19 PM subjects compared to CYP2C19 NM subjects. 


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No SAEs, deaths, or AEs leading to study discontinuation occurred during the study. All TEAEs 
(n=11) were mild in severity. One subject of CYP2C19 NM experienced two TEAEs of chest 
discomfort, one of which was judged to be related to mavacamten, and the other was unrelated 
to mavacamten. Additional 3 TEAEs were judged to be investigational drug-related (1 
palpitations in a subject of CYP2C19 NM, 1 constipation and 1 diarrhea in 2 subjects of 
CYP2C19 PM). Others were judged to be unrelated to the investigational drug (3 upper 
respiratory tract infections, including 1 cough, 1 oropharyngeal pain and 1 upper-airway cough 
syndrome). 
The PK data from MYK-461-011 and MYK-461-012 were illustrated below: 
Table 3 Summary of PK Parameters from Study MYK-461-011 and Study MYK-461-
012 
Study 
MYK-461-011 
MYK-461-
012 
Parameter 
Statistic 
Cohort 1 
Cohort 2 
Cohort 3 
Cohort 4 
Cohort 2 
5 mg 
15 mg 
25 mg 
25 mg 
15 mg 
Japanese 
Subjects 
Japanese 
Subjects 
Japanese 
Subjects 
Caucasian 
Subjects 
Asian 
Subjects 
IM 
IM 
UM/RM/ 
NM 
UM/RM/ 
NM 
PM 
N=4 
N=8 
N=8 
N=8 
N=8 
Cmax 
(ng/mL) 
GM 
(gCV %) 
141.3 
(15.5) 
289.0 
(19.8) 
504.0 
(18.3) 
515.8 
(28.6) 
489.0 
(31.4) 
Tmax 
(h) 
Median 
1.5 
1.0 
1.5 
1.5 
0.750 
AUC(0-last) 
(h*ng/mL) 
GM 
(gCV %) 
5897 
(28.8) 
14660 
(25.4) 
16890 
(30.8) 
18820 
(49.6) 
35310 
(13.6) 
AUC(0-inf) 
(h*ng/mL) 
GM 
(gCV %) 
6277 
(28.7) 
15410 
(27.4) 
17370 
(34.0) 
19280 
(53.2) 
42800 
(20.3) 
T½ 
(h) 
Mean 
(CV %) 
222.2 
(24.6) 
221.5 
(23.0) 
153.8 
(50.5) 
155.7 
(48.2) 
571.6 
(24.5) 
CL/F 
(mL/h) 
Mean 
(gCV %) 
821.3 
(29.5) 
1006 
(29.2) 
1505 
(30.6) 
1425 
(40.6) 
357.1 
(22.1) 
Vd,z/F 
(mL) 
Mean 
(gCV %) 
251200 
(16.4) 
310900 
(26.0) 
306800 
(30.8) 
276600 
(26.1) 
282300 
(14.9) 
 
1.3 Known and Potential Benefits and Risks 
There is no clinical benefit for the healthy subjects enrolled in the current study. 
Based on nonclinical data and the available clinical data, four important risks have been 
described in the latest Development Safety Update Report with data lock point of 30-Oct-2020: 
heart failure due to systolic dysfunction defined as symptomatic LVEF < 50%, teratogenicity, 
QT prolongation, increased risk of heart failure due to interaction with CYP2C19 and potent 
CYP3A4 inhibitors. 
➢  Heart failure due to systolic dysfunction defined as symptomatic LVEF < 50% 
Data across nonclinical toxicology studies have shown that doses of mavacamten exceeding 
therapeutic levels can lead to reduced cardiac function, decreased blood pressure, 
compensatory increases in heart rate, and death. Clinical data has shown that dose-dependent, 
on-target reductions in LVEF have been monitorable with use of echocardiograms, reversible 


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with temporary or permanent discontinuation of treatment, and observed in the setting of 
mavacamten treatment alone or with concomitant conditions frequently observed in HCM, 
such as atrial fibrillation. 
In patients with HCM, mavacamten’s on-target mechanism of action reduces LVEF and may 
cause systolic dysfunction with LVEF < 50% with or without symptoms of left heart failure. 
Patients with a serious intercurrent illness or arrhythmia (e.g., atrial fibrillation or other 
uncontrolled tachyarrhythmia) may be at greater risk of systolic dysfunction. Data from MYK-
461-006, conducted in subjects with nHCM, demonstrated that those who experienced 
decreases in LVEF returned to normal levels after interruption or discontinuation of study 
treatment. In the EXPLORER-HCM study (Study MYK-461-005), 7 subjects (5.7%) in the 
mavacamten group and 2 subjects (1.6%) in the placebo group experienced reversible 
reductions in LVEF < 50% while on treatment. In all 7 subjects treated with mavacamten, 
LVEF recovered following temporary interruption of dosing or was diagnosed at the end of the 
30-week treatment period and recovered at Week 38. All subjects with an event of LVEF < 50% 
completed the study, with favorable changes from baseline in at least one key efficacy endpoint. 
➢ Teratogenicity 
Oral administration of mavacamten in reproductive toxicity pre-clinical studies in 2 species 
(rats, rabbits) resulted in developmental toxicities (post-implantation loss, decrease in fetal 
body weight, and skeletal malformations in rats; visceral and skeletal malformations in rabbits), 
which were suggestive of a teratogenic potential of mavacamten. There are no clinical data on 
the safety of mavacamten during pregnancy, and highly effective contraception is required in 
the ongoing clinical studies. 
➢ QT Prolongation 
Across all clinical studies in HCM patients, there has been no indication of a mavacamten-
induced QTc prolongation and/or of a concentration-dependent increase in QTc. In the 
EXPLORER-HCM study, baseline QTc interval was 440 ms in the mavacamten group and 443 
ms in the placebo group. 22 (17.9%) patients in the mavacamten group and 20 (15.6%) patients 
in the placebo group had a change from baseline in QTcF interval of > 30 ms, the majority of 
whom did not have an ICD/pacemaker. This included 2 (1.6%) patients in the mavacamten 
group and 3 (2.3%) in the placebo group with a change > 60 ms. For 1 (0.8%) patient in the 
mavacamten group and 2 (1.6%) in the placebo group, maximum changes from baseline were > 
15%. 
Prolonged exposure to mavacamten in healthy animals resulted in a moderate prolongation of 
the QTc interval. Animal studies have suggested that such QTc prolongation occurs as a normal 
electrophysiological adaptation of healthy ventricles to the induced sustained mechanical 
changes, as mavacamten shows negligible direct (blockade) and/or indirect (trafficking) effects 
on human ether-a-go-go related gene (hERG) channels at the cellular level. 
Consistent with non-clinical findings, in clinical studies involving healthy volunteers, sustained 
exposure to mavacamten led to marked depression of systolic dysfunction, which was 
associated with moderate concentration-dependent QTc prolongation (> 10 ms). No acute QTc 
changes have been observed at comparable (or higher) exposures during single-dose studies. 
Safety testing in other mammalian species has shown that dose-limiting toxicities are 
associated with exaggerated pharmacological effect rather than off-target effects. 


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➢ Increased risk of heart failure and lack of effect due to interaction with CYP2C19 
and potent CYP3A4 inhibitors 
Mavacamten is primarily metabolized by CYP2C19 and CYP3A4. Starting or increasing the 
dose of any CYP2C19 or potent CYP3A4 inhibitor may increase the risk of systolic 
dysfunction. Stopping or decreasing dose of a CYP2C19 or potent CYP3A4 inhibitor may lead 
to a loss of therapeutic response to mavacamten. The potential for drug interactions with a CYP 
2C19 inhibitor, including over-the-counter medications (such as omeprazole or esomeprazole), 
must be considered prior to and during mavacamten therapy. A list of prohibited medications 
for subjects in mavacamten clinical trials are utilized for screening and monitoring of subjects 
in the program. 
Notably, clinical studies for mavacamten are ongoing. New safety information could emerge 
from ongoing clinical studies, which would be reflected in the IB and DUSR. 


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2. Rationale for the Study and Administration 
2.1 Rationale for the Study 
The sponsor is developing mavacamten, a novel, small molecule, allosteric inhibitor of cardiac-
specific and selective myosin, for the treatment of patients with symptomatic oHCM, a 
condition with significant unmet medical need. Currently, clinical studies in healthy subjects 
and patients with oHCM have been conducted in the United States, the European Union, the 
United Kingdom, Australia, and Japan. Future studies are expected to include study sites in 
China, so a Phase 1 clinical study is warranted to confirm the obtained tolerability and PK data 
of mavacamten in Chinese subjects. That study is commonly referred to as an ethno-bridging 
study. 
Mavacamten is metabolized in part by CYP2C19, an enzyme with genetic polymorphism. The 
incidence of the PM phenotype for CYP2C19 ranges from around 2% in the Caucasian 
population to around 12% in the Asian population [24]. Limited data obtained thus far have 
indicated that the exposure to mavacamten may be increased by approximately 3-fold in 
subjects of CYP2C19 PM compared to subjects of CYP2C19 NM. The current study is 
designed to determine the exposure to mavacamten in healthy adult Chinese subjects with 
different genotypes of CYP2C19. 
2.2 Rationale for Dose Selection 
Previous study (MYK-461-011) had demonstrated that Japanese and Caucasian subjects with 
genotypes of CYP2C19 UM, RM or NM showed similar PK profiles after receiving a single 
25 mg dose of mavacamten. The drug was well-tolerated in all subjects. 
Meanwhile, the PK profile of a single dose of 15 mg mavacamten was assessed in subjects of 
CYP2C19 IM and CYP2C19 PM in studies MYK-461-011 and MYK-461-012. 
To bridging these PK data, a PK study in healthy Chinese adults with CYP2C19 genotypes of 
UM, RM, NM, IM or PM will be implemented. Subjects with CYP2C19 genotypes of UM, 
NM, or RM will receive a single dose of 25 mg mavacamten (Cohort 2) as in MYK-461-011; 
subjects with CYP2C19 genotypes of IM or PM will receive a single dose of 15 mg 
mavacamten as in MYK-461-011 and MYK-461-012; in addition, subjects with CYP2C19 
genotypes of UM, NM, or RM will also receive a single dose of 15 mg mavacamten, in order 
to evaluate the PK profiles of mavacamten in subjects with different genotypes (Cohort 1/3/4) 
at the same dose (15 mg). 


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3. Objectives 
Primary: 
To evaluate the PK of a single oral dose of mavacamten in healthy adult Chinese subjects with 
different CYP2C19 genotypes. 
Secondary: 
To evaluate the safety and tolerability of a single oral dose of mavacamten in healthy adult 
Chinese subjects with different CYP2C19 genotypes. 
Exploratory: 
To evaluate the population PK. 


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4. Overall Study Design 
4.1 Study Design 
This is an open-label, parallel-group, single-center Phase 1 clinical trial. 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 oral dose of mavacamten to evaluate its PK profile. 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. 
 
Figure: Overall Study Design 
Abbreviations: CYP = Cytochrome P450; IM = intermediate metabolizer; NM = normal metabolizer; PM = 
poor metabolizer; RM = rapid metabolizer; UM = ultra- rapid metabolizer.  
4.2 Study Periods 
The overall study period for each subject is up to 16 weeks. The study periods are as follows: 
 
Pre-screening period: up to 28 days (Day -43 to Day -15); 
 
Screening period: up to 13 days (Day -14 to Day -2); 
 
In-house period: day -1 to Day 3; 
 
Outpatient period: Day 4 to Day 75. 
 
End of study visit: Day 75. 


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4.3 Study Procedures 
4.3.1 Pre-screening Period (Day -43 to Day -15, up to 28 days) 
Subjects who sign the pre-screening ICF will enter the pre-screening period to determine their 
CYP2C19 genotypes. 
2 mL whole blood will be collected at each following time point for CYP2C19 genotypes 
analysis enter the pre-screening period (See Table 2). Refer to the relevant laboratory 
management manual for details of blood sample processing. 
4.3.2 Screening Period (Day -14 to Day -2, up to 13 days) 
After determining their genotypes, subjects who sign the main ICF will enter the screening 
period to receive screening examinations. Screening assessments can be repeated for one more 
time at the investigator’s discretion within the screening window. 
4.3.3 In-house Period (Day -1 to Day 3) 
Eligible subjects will be divided into 4 parallel cohorts based on their CYP2C19 genotypes 
(Cohort 1 and Cohort 2: CYP2C19 UM, RM, or NM; Cohort 3: CYP2C19 IM; Cohort 4: 
CYP2C19 PM). 
Subjects will be admitted to the CRU the day before dosing (Day-1) and receive a single oral 
dose of mavacamten (Cohort 1: 15 mg; Cohort 2: 25 mg; Cohort 3: 15 mg; Cohort 4: 15 mg) 
on Day 1. For subjects with CYP2C19 UM, RM, or NM, enrollment Cohort 1 first followed 
by Cohort 2, subjects can be enrolled to Cohort 3 and Cohort 4 in parallel. They will remain in 
the CRU until Day 3 (48 hours after administration of mavacamten) for PK and safety 
assessments. 
4.3.4 Outpatient Period (Day 4 to Day 75) 
Subjects who have finished the examinations on Day 3 will enter the outpatient period. 
Outpatient visits will occur on Days 7, 10, 14, 21, 28, 35, 45 and 60 to collect blood samples 
and perform safety assessments. 
4.3.5 End of Study visit (Day 75) 
End of study (EOS) Visit will occur on Day 75 to complete the final safety examination and 
obtain the last blood samples for PK assessment. 
4.3.6 Unscheduled Visits 
Subjects who have safety concerns should return to the CRU for unscheduled visit at the 
investigator’s discretion. Unscheduled visits may be conducted for the collection of vital signs, 
ECGs, and/or the assessment of AEs. All information collected from unscheduled visits will be 
recorded in the eCRF and included in the clinical database. 
4.3.7 Missed Visits 
If a visit is missed, the visit and relevant assessments should be rescheduled as close as possible 
to the original date. 
4.4 Behavioral Restrictions on Subjects 
The following behavioral restrictions apply to the specified times throughout this clinical trial. 
If a subject does not comply with these restrictions or tests positive in any laboratory tests (e.g., 
drug, alcohol, pregnancy), he or she may be excluded or withdrawn from the study. 


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1) Subjects should not engage themselves in unaccustomed intensive exercises starting from 
72 hours prior to the first dose to the EOS Visit; 
2) Subjects will be required to abstain themselves from blood or plasma donation starting 
from the screening period to 3 months after the EOS Visit. 
3) Subjects will have standardized meals during their stay in the CRU. 
4) Subjects will be asked to abstain from alcohol starting from 48 hours before Day -1 to the 
EOS Visit. 
5) Subjects will be asked to abstain from grapefruit or grapefruit juice, Seville oranges, and 
quinine (e.g., tonic water) starting from Day -1 to the EOS Visit; 
6) During their stay in the CRU, subjects will be permitted to smoke up to 5 cigarettes per 
day. 
7) Contraception requirements are described in Section 9.2. 


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5. Study Population 
5.1 Study Population 
Approximately 44 healthy adult Chinese subjects with different CYP2C19 genotypes will be 
enrolled in this clinical trial. This is a single-center study. Subjects will be divided into 4 
cohorts. 
• 
Cohorts 1 and 2: 12 healthy adult Chinese subjects to ensure that data will be obtained for 
at least 10 subjects; with their CYP2C19 genotypes being: 
• 
CYP2C19 UM: *17/*17 or 
• 
CYP2C19 RM: *1/*17 or 
• 
CYP2C19 NM: *1/*1; 
• 
Cohort 3: 12 healthy adult Chinese subjects to ensure that data will be obtained for at least 
10 subjects; with their CYP2C19 genotypes being: 
• 
CYP2C19 IM: *1/*2 or *1/*3; 
• 
Cohort 4: 8 healthy adult Chinese subjects to ensure that data will be obtained for at least 
6 subjects; with their CYP2C19 genotypes being: 
• 
CYP2C19 PM: *2/*2, *3/*3, or *2/*3. 
5.2 Subject's Screening Number 
All subjects who provide an informed consent will be assigned a screening number and a 
grouping number to distinguish them from one another as per the rules given below. The 
same screening number will be used from the time of informed consent to the EOS. 
Pre-Screening No.: PXXX; 
XXX: a serial number assigned to a subject who gives the informed consent at the study site. 
Screening No.: SYYY 
YYY: a serial number assigned to a subject enrolled into screening period. 
Grouping No.: A/B/C/DZZZ 
ZZZ: a serial number assigned to a subject enrolled into different groups (A: cohort 1; B: 
cohort 2; C: cohort 3; D: cohort 4), i.e., A005 as cohort 1 the fifth subject. 
Replacement subjects will be assigned a subject number corresponding to the number of the 
subject he/she is replacing plus 100 (eg, Subject 105 replaces Subject 005) 
5.3 Inclusion Criteria 
Subjects can be enrolled in the study if they meet all of the following criteria: 
1) Male or female between the ages of 18 and 60 (inclusive) at screening (one sex not less 
than 25% each cohort); 
2) 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; 


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3) With a BMI between 18 kg/m2 and 30 kg/m2 (inclusive) at screening; 
4) With a resting LVEF ≥ 55% by echocardiography at screening; 
5) Healthy as determined by medical history, physical examination, vital signs, and laboratory 
test parameters (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 judged to be clinically insignificant. Screening assessments can be 
repeated for one more time at the investigator’s discretion within the screening window; 
6) 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 IMP: 
• 
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; 
• 
IUD; 
• 
IUS; 
• 
Bilateral tubal ligation; 
• 
Females who have been surgically sterilized for more than 6 months or 
postmenopausal for more than 1 year. Permanent sterilization includes documented 
hysterectomy, bilateral oophorectomy, bilateral salpingectomy, and/or bilateral tubal 
ligation for at least 6 months prior to screening. Females are considered as 
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; 
7) Male partners of female subjects must also adopt a contraceptive method (e.g., barrier, 
condom or vasectomy) from screening to 5 months after administration of the 
investigational drug. 
8) 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 the screening procedure. 
5.4 Exclusion Criteria 
Subjects must not be enrolled in the study if they meet any one of the following criteria: 
1) History of clinically significant arrhythmia, LV systolic dysfunction, or coronary artery 
disease, or QTc >450 ms at screening and on Day; 
2) 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; 
3) Positive serologic tests at screening for infections with HIV antibody, HCV antibody, or 
HBV surface antigen at screening;  
4) Vital sign meet any of the following criteria: a) ear temperature was greater than 37.5 ℃; 
b) heart rate was greater than 100 beats / min or less than 50 beats / min; c) systolic blood 
pressure was greater than 139 mmHg or less than 90 mmHg; d) diastolic blood pressure 
was greater than 90 mmHg or less than 50 mmHg at screening and on Day -1; 


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5) Subjects who have taken prescription medications within 28 days prior to screening or 5 
times of T1/2 (if known), whichever is longer; or those who have taken over-the-counter 
medications (including herbal medications and nutritional supplements) within 14 days 
prior to screening or 5 times of T1/2 (if known), whichever is longer (acetaminophen up to 
1.5 g per day is allowed); 
6) History or evidence of any other clinically significant abnormalities, conditions, or 
diseases (with the exception of those outlined above) 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; 
7) 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; 
8) Positive test for alcohol or drug abuse at screening and on Day -1; 
9) Use of tobacco exceeding 10 cigarettes per day or nicotine-containing products of 
equivalent amount within 28 days prior to screening; 
10) 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); 
11) Prior exposure to mavacamten; 
12) 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; 
13) Unable to comply with the study restrictions/requirements, including the number of 
required visits to the clinical site; 
14) Had donated over or lost 400 mL blood in 60 days or plasma in the last 2 weeks prior to 
the screening visit; 
15) Known infection of COVID-19 (i.e., positive for polymerase chain reaction) within 6 
months prior to screening.  
16) Unsuitable to participate in the study as judged by the investigator; 
5.5 Withdrawal & Replacement of Subjects and Termination of Clinical Trial 
5.5.1 Withdrawal of Subjects from Clinical Trial 
Subjects are free to revoke their informed consent and withdraw from the study at any time and 
for any reason. If a subject chooses to withdraw from the study, the investigator will attempt to 
obtain the assessments listed for the EOS Visit (see Table 1). 
The investigator or sponsor may withdraw a study subject from the study for any of the 
following reasons, including but not limited to the following: 
• 
Noncompliance with study procedures/restrictions; 
• 
The sponsor terminates the clinical trial; 
• 
At discretion of the investigator 


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In all cases, the reason(s) for study withdrawal will be recorded in the source document and in 
the appropriate eCRF. 
 


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5.5.2 Subject Replacement 
Subjects who withdraw or discontinue the clinical study due to other reasons other than AEs 
may be replaced at the discretion of the investigator, and should be discussed with sponsor 
before replacement if possible. 
5.5.3 Discontinuation of the Clinical Study 
The sponsor retains the right to terminate the study. Specific circumstances that may lead to 
discontinuation of the study include, but are not limited to: 
• 
Request by Ethics Commission (EC), Center for Drug Evaluation (CDE) or the 
National Health Commission of the Peoples' Republic of China to discontinue the 
study; 
• 
Unsatisfactory subject enrollment; 
• 
The incidence or severity of AEs in this or other studies indicating potential health 
hazard caused by the study dosing. 


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6. Investigational Drug 
6.1 Basic Information of Mavacamten 
Table 4 Investigational Drug 
Name of Study Drug 
Mavacamten 
Dosage Form 
Capsules 
Strength 
10 mg and 15 mg 
Dosage 
Single dose of 15 mg or 25 mg 
Route of Administration 
Oral 
Investigational Medicinal Product 
(IMP) 
Mavacamten 
Supplier 
Sponsor 
Packaging and Labeling 
Refer to Section 6.2 
Abbreviations: IMP = investigational medicinal product; 
6.2 Preparation, Handling, Storage, and Accountability 
The investigator or designee must confirm appropriate temperature conditions were maintained 
during transit for all investigational drug received and that any discrepancies with the relevant 
regulations are reported and resolved before use of the investigational drug. 
Only eligible subjects may receive investigational drug, and only authorized study staff may 
supply or administrate investigational drug. All investigational drug must be stored in a secure 
and monitored area in accordance with the labeled storage conditions with access limited to the 
investigator and authorized site staff. 
The investigator/designee is responsible for investigational drug accountability, reconciliation, 
and record maintenance (i.e., receipt, reconciliation, and final disposition records). Further 
guidance and information for the final disposition of unused investigational drug are provided 
in the related pharmacy manual. 
➢ Formulation, Packaging, and Labeling  
Mavacamten capsules is blue opaque capsules printed with a yellow band on the body and 
black band on the cap. Each capsule contains white or off-white powder. Mavacamten capsules 
are supplied in 2 strengths: 10 mg and 15 mg. 
The mavacamten capsules have been manufactured according to current Good Manufacturing 
Practice (cGMP) regulations. They will be supplied in high-density polyethylene bottles with 
induction seals and child-resistant caps at 30 count per bottle. All investigational drug will be 
labeled according to applicable local regulatory guidelines. 
The mavacamten capsules must be stored at 2°C to 25°C (36°F to 77°F) in the packaging 
supplied by the sponsor. Study medication at the study site will be stored in a secure area with 
access limited to authorized study personnel. 
6.3 Dose Regimen 
Subjects receive a single dose of mavacamten on Day 1; 
Cohort 1: 15 mg (15 mg capsule × 1); 


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Cohort 2: 25 mg (10 mg capsule × 1 and 15 mg capsule × 1); 
Cohort 3: 15 mg (15 mg capsule × 1); 
Cohort 4: 15 mg (15 mg capsule × 1). 
6.4 Administration 
All subjects will receive mavacamten in an open-label manner. 
The IMP for this clinical study is mavacamten. Study medication throughout this protocol 
refers to IMP as well as any other protocol-required medications (note that for this protocol, 
there are no other required study medications). 
Mavacamten will be administered at the CRU by a trained, qualified staff member. Subjects 
will receive a single dose of mavacamten on Day 1. 
Subjects should take mavacamten with approximately 240 mL of water. Subjects should fast 
overnight (for at least 8 hours) before taking mavacamten and should not eat any food until 3 
hours after taking mavacamten. Water will be allowed except for 1 hour before and after dosing. 
6.5 Dosing Compliance 
Mavacamten will be administered by a trained, qualified CRU staff member on Day 1. 
6.6 Prior and Concomitant Therapy 
6.6.1 Prior Therapy 
At the time of signing the main ICF, subjects will be asked about their medication history over 
the previous 28 days, including prescription and nonprescription medications, herbal 
medications, vitamins, and minerals. 
If a subject has not taken any prescription medication within 28 days or 5 times of half-life (if 
known), whichever is longer, of screening or any over-the-counter medication (including 
herbal preparations and nutritional supplements, but excluding acetaminophen up to 1.5 g per 
day) within 14 days or 5 times of half-life (if known), whichever is longer, of screening, the 
individual may proceed to the screening assessment. 
6.6.2 Concomitant Medications 
All concomitant medications, whether prescription or over-the-counter, vitamin and/or mineral 
supplements, herbs, and medications taken for an AE or study procedure (e.g., biopsy). should 
be documented in the medical notes and entered into eCRF, including start/stop dates, route, 
and indication. 
6.6.3 Prohibited Medications 
All prescription medication is prohibited from 28 days before screening through the EOS Visit, 
and all over-the-counter medication (including herbal preparations and nutritional supplements, 
but not including up to 1.5 g acetaminophen daily) is prohibited from 14 days before screening 
through the EOS Visit. 


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7. Study Assessments 
The investigator is responsible for ensuring that all staff involved in the study are familiar and 
comply with the content of this section. 
The study procedures to be performed during the study are described below. Additional details 
are provided in Table 1 of this document. When several assessments are to be conducted at the 
same time point, the preferred order of assessments is ECG, vital signs, sample collection for 
PK and laboratory assessments. The order of assessments may vary slightly at specific time 
points to facilitate the most contemporaneous performance of the required assessments. 
Unscheduled or additional safety assessments may be performed if necessary, in the opinion of 
the investigator. 
For assessments that require the subjects to be in a semi-recumbent or supine position, 
assessments should be conducted with subjects in the same position at all time-points. 
7.1 PK Assessments 
PK Blood Sampling Schedule 
3mL whole blood will be collected at each following time point for PK analysis. 
Blood samples will be obtained to determine mavacamten concentrations at pre-dose (within 
60 min before dosing), 10 min, 20 min, 30 min, 45 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 8 h, 12 h, 24 
h, and 48 hours after dosing of mavacamten. Additional blood samples will be collected at Days 
7, 10, 14, 21, 28, 35, 45, 60 and 75 (See Table 2). 
PK Blood Sample Processing 
Refer to the relevant laboratory management manual for details of blood sample processing. 
7.2 Safety Assessments 
Safety will be assessed throughout the study (Table 1). Safety assessments include physical 
examinations, vital signs, ECGs, observed and subject-reported AEs, and safety laboratory 
results. 
Any abnormal findings judged by the investigator to be clinically significant will be recorded 
as an AE (See Section 8.1). 
Physical Examination 
Physical examinations will be conducted at screening Day-1, Day 3 and at the EOS Visit. A 
complete physical examination will be conducted at screening and the EOS Visit. An 
abbreviated physical examination will be conducted on Days -1 and 3 (Table 1). 
A complete physical examination includes assessments of general appearance, skin, head and 
neck, mouth, lymph nodes, thyroid, abdomen, and musculoskeletal, cardiovascular, 
neurological, and respiratory systems. Brief physical examination included cardiovascular and 
respiratory 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. 
Vital Signs 
Vital signs will be assessed at each study visit and include temperature, HR, respiratory rate, 
and systolic and diastolic BP in a supine position after 5 minutes of rest (Table 1). While the 


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subject is in the CRU, vital signs will be taken upon rising in the morning. On Day 1, vital 
signs should be collected within 3 h before IMP dosing. 
12-lead ECG 
Twelve-lead ECG evaluations will be performed after 10 minutes of rest in the supine position 
at screening, Day -1, Day 1 (pre-dose, within 3 h before dosing, and at 2 h±30 min post-dose), 
Day 3, Day 28, Day 60 and the EOS Visit (Table 1). Parameters to be evaluated include, but 
are not limited to: HR, rhythm, PR interval, QRS interval, QT interval, P wave, QRS complex, 
T wave morphology, ST segment displacement, etc. 
The investigator will judge the overall interpretation as normal or abnormal with clinical 
significance or abnormal with no clinical significance. The investigator will review the ECG 
with any other clinical findings, subject's medical history, and laboratory data to determine the 
clinical significance of the findings. 
The investigator may add extra 12-lead ECG safety assessments if there are any clinically 
significant abnormal findings or if the investigator considers it is required for any other safety 
reason. These assessments should be recorded as an unscheduled assessment. 
Other Safety Assessments 
Refer to Section 8.1 for information on AE assessment and Section 6.6.2 for concomitant 
therapy assessments. 
Safety laboratory results will be assessed in an ongoing manner. Laboratory parameters are 
provided in Appendix 1. 


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8. Assessment, Recording and Reporting of Adverse Events 
8.1 Definitions 
8.1.1 Adverse Events 
An AE is any untoward medical occurrence in a subject after receiving the investigational 
product and does not necessarily have a clear causal relationship with the investigational drug. 
An AE can therefore be any unfavorable and unintended sign (e.g., tachycardia, enlarged liver, 
clinically significant or abnormal laboratory result), subject-reported symptom (e.g., nausea, 
chest pain), or evidence of any disease activity temporally associated with the use of a study 
medication, whether or not related to the use of the study medication. 
In clinical studies, an AE can include an undesirable medical event occurring at any time after 
the subject has signed pre-screening ICF and main ICF, even if no study drug has been 
administered before the occurrence of the AE. For this study, only blood sampling study 
procedure related AEs (e.g., blood sampling) will be collected during pre-screening and 
screening period. 
An AE or SAE may also result from procedures specified in the protocol. 
For sponsor to collect more information about clinically significant laboratory results or 
diagnostic tests (e.g., hematology, ECG), at a min, the following abnormalities should be 
captured in the AE eCRF: 
• 
Any test result that meets the definition of a SAE; 
• 
Any clinically significant test abnormality (e.g., >3 × deviation from the upper or 
lower limit of the analyzing laboratory reference range, or as otherwise specified in 
the protocol); 
• 
Any test abnormality that requires the subject to receive specific corrective therapy, 
close observation, more frequent follow-up assessment, or further diagnostic 
investigation. 
The following additional points should be considered for AEs: 
• 
Preplanned medical surgeries or procedures 
− 
Preplanned surgeries or procedures that were scheduled prior to signing of ICF are 
not considered as AEs. 
• 
Hospitalization for preplanned surgeries or procedures 
• 
Overdose 
− 
Cases of overdose with any medication without manifested side effects are not 
considered AEs. 
The term AE is used generally to include any AE whether serious or nonserious. 
Events that do not meet the definition of AE include the following: 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
led to the procedure is the AE; 
• 
Situations in which an untoward medical occurrence did not occur (admission to a 
hospital due to medical insurance and/or convenience); 


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8.1.2 Serious Adverse Events (SAEs) 
A SAE is an AE that fulfills one or more of the following criteria in the opinion of the 
investigator or sponsor: 
• Results in death; 
• Is immediately life-threatening (places the subject at immediate risk of death from the 
event as it occurred); 
• Requires subject hospitalization or prolongation of existing hospitalization; 
• Resulting in persistent or significant disability or incapability or substantial disruption 
of the ability to conduct normal life functions; 
• Results in a congenital abnormality or birth defect. 
Is an important medical event that may not result in death, be life-threatening, or require 
hospitalization, but may be considered a SAE when, based upon appropriate medical judgment, 
it may require medical or surgical intervention to prevent one of the outcomes listed above. 
8.2 Collection and Reporting of AEs 
8.2.1 Collection Time 
AEs will be assessed from the time the subject signs pre-screening ICF through the end of the 
study. However, only study procedure related AEs (e.g., blood sampling) will be collected 
during the pre-screening and screening period. 
8.2.2 Description 
All AEs spontaneously reported by the subject or reported in response to the open question 
from the study personnel "Have you had any health problems since you were last asked?", or 
revealed by observation will be collected and recorded in the eCRF. 
When collecting AEs, the recording of diagnoses is preferred (when possible) to recording a 
list of signs and symptoms (e.g., anemia, not haemoglobin decreased). However, if a diagnosis 
is known and there are other signs or symptoms that are not generally part of the disease, the 
diagnosis and each sign or symptom will be recorded separately. 
Death is an outcome and not the name of the event. In this situation, the event that led to the 
death is the name of the event. 
8.2.3 Start Date/Time and Stop Date/Time 
The date (time, if applicable) that the AE started and the date (time, if applicable) that the event 
ended will be recorded. For events that continue for long periods of time, recording the end 
date as the day the event stabilized will also be acceptable. 
8.2.4 Relationship to Study Drug 
The investigator should assess causality to be "related" or "unrelated" by answering the 
question "Is there a reasonable possibility that the AE may have been caused by the IMP/study 
medication?". 
The following factors can be used in consideration of causality assessment: 
• 
Dechallenge: Did the event abate after study medication was reduced or interrupted? 


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• 
Rechallenge: Did the event reappear after study medication was reintroduced? 
• 
Whether there is a reasonable temporal relationship between the AE and 
administration (or procedure); 
• 
Confounding risk factors; 
• 
Amount and duration of study drug exposure; 
• 
Concomitant medications. 
8.2.5 Intensity 
The  following criteria will be used for evaluation of AE intensity: 
Mild; asymptomatic or mild; clinical or diagnostic observations only; intervention not indicated. 
Moderate; minimal, local, or non-invasive treatment indication, age-related instrumental 
activities of daily living limited*. 
Severe: medically significant but not immediately life-threatening; leading to hospitalization 
or prolongation of hospitalization; disabling; personal activities of daily living are limited**. 
Life-threatening, urgent treatment indicated. 
Death related to AEs. 
*Instrumental activities of daily living refer to preparing meals, shopping for groceries or 
clothes, using the telephone, managing money, etc. 
**Self-care activities of daily living refer to bathing, dressing and undressing, eating, washing, 
taking medicine, etc., and not bedridden. 
 
8.2.6 Seriousness 
Record SAEs or indicate them to be non-serious according to the criteria described in Section 
8.1.2. 
It is important to distinguish between category (AE vs SAE) and intensity (mild, moderate, or 
severe) of AEs. 
Severity is a variable for intensity assessment (Section 8.2.5), whereas seriousness is defined by 
the criteria under Section 8.1.2.。 
An AE of severe intensity may not be necessarily defined as serious. For example, nausea that 
persists for several hours may be considered severe nausea but not a SAE. On the other hand, 
a stroke that results in only a limited degree of disability may be considered a mild stroke but 
would be a SAE. 
 
 


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8.2.7 Outcomes 
Record the outcome of the AEs based on the options provided in the eCRF. The outcome of a 
SAE should be recorded in the SAE form. 
8.3 Reporting and Assessment of SAE 
All SAEs occurring after the administration (defined as the period from the first administration 
of study drug to the EOS regardless of causality) will be reported by the investigator or designee 
to the sponsor/designee within 24 hours of knowledge of the event or sequelae. Deaths and 
SAEs occurring after the end of the study and considered related to study medication or study 
procedure must also be reported. SAE reporting instructions are provided in the related manual. 
8.4 Reporting of Adverse Events of Special Interest  
Symptomatic overdose, outcomes of a pregnancy, and LVEF≤30% as determined by local site 
are considered as Adverse Events of Special Interests (AESIs). 
AESIs are required to be reported by the investigator to the sponsor within 24 hours. 
8.5 Reporting of Drug-induced Liver Injury 
To facilitate appropriate monitoring for signals of drug-induced liver injury (DILI), cases of 
concurrent aspartate/alanine (AST/ALT) and total bilirubin (TBL) elevation according to the 
criteria specified (3 × upper limit of normal [ULN] for AST/ALT and 2 × ULN for TBL in 
participants with no underlying liver disease and eligibility criteria requiring normal liver 
function at baseline) require to be reported to sponsor as an SAE within 24 hours of discovery 
or notification of the event (ie, before additional etiologic investigations have been concluded). 
Other events of hepatotoxicity and potential DILI are to be reported as SAEs if they meet the 
criteria for an SAE. 
8.6 Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each subject 
at subsequent visits/contacts. All AEs, SAEs, and AESIs will be followed until resolution, 
stabilization, unless the event is otherwise explained, or the subjects considered lost to follow-
up at the end of the study. 
Any AEs that are unresolved at the subject's last visit in the study are followed by the 
investigator with routine medical practice until resolved or stabilized and are considered 
irreversible, or the subject has died. 
The sponsor retains the right to request additional information from any subject who also has 
an AE/SAE at the end of the study, if judged necessary. 
8.7 Reporting and Follow-up of Pregnancy 
Pregnancies occurring at any time between study drug administration and up to 5 months after 
study drug administration must be reported for female subjects or female partners of male 
subjects. The investigator is responsible for informing the sponsor within 24 hours of 
knowledge of the pregnancy even if no AE has occurred per the reporting guidelines. The 
subject will be asked to provide information on the outcome of the pregnancy through 6 months 
after birth or details of premature termination. Spontaneous miscarriage and congenital 
abnormalities will be reported as SAEs. Consent to report information regarding pregnancy 


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and pregnancy outcomes should be obtained from the partner of the male subject. 
Pregnancy of a subject or partner of a male subject should be entered in the Pregnancy 
Notification CRF. Pregnancy follow-up should be documented on a follow-up form and be 
reported to the sponsor or designee within 24 hours. 
Any SAE experienced by a subject during pregnancy must be reported using a SAE form within 
24 hours. 
 
 


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8.8 Safety Reporting to Investigators, Institutional Review Boards, Independent Ethics 
Committees, and Regulatory Authorities 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical study. The sponsor 
will conduct safety reports to regulatory authorities, the institutional review boards 
(IRBs)/independent ethics committees (IECs) and investigators in compliance with country-
specific regulatory requirements. 
Suspicious and Unexpected Serious Adverse Reactions (SUSARs) are SAEs that qualify for 
mandatory expedited reporting to regulatory authorities when the SAE is suspected to be 
caused by the study drug and is considered unexpected (i.e., not defined as expected in the 
current IB, clinical study protocol). In this case, the sponsor/designee will report to the relevant 
regulatory authority and forward a formal notification describing the SUSAR to investigators, 
according to regulatory requirements. Each investigator must then notify his/her IRB/IEC of 
the SUSAR as required by local regulatory authorities and in accordance with their IRB/IEC 
policy. 
An investigator who receives an investigator safety report describing a SUSAR or other 
specific safety information (e.g., summary or listing of SUSARs) from the sponsor will review 
and then file it along with the IB and will notify the IRB/IEC, if appropriate according to local 
requirements. 


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9. Risks and Precautions 
9.1 General Risks 
Based on nonclinical data and the available clinical data, four important risks have been 
described: heart failure due to systolic dysfunction defined as symptomatic LVEF < 50%, 
teratogenicity, QT prolongation, increased risk of heart failure due to interaction with 
CYP2C19 and potent CYP3A4 inhibitors. Please refer to Section 1.3 for details of relevant 
risks. Corresponding risk control measures have been developed by the sponsor for these risks, 
including collection and assessment of AEs, setting of corresponding subject eligibility criteria 
and dose interruption/discontinuation criteria, close monitoring of subjects' indicators during 
the study, etc. Details can be found in the corresponding sections. 
9.2 Pregnancy 
9.2.1 Avoidance of Pregnancy 
Women of childbearing potential must use appropriate methods of birth control. Women of 
non-childbearing potential are defined as women who are permanently (surgically) sterilized 
or are postmenopausal. Permanent sterilization includes hysterectomy, bilateral oophorectomy, 
and 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 FSH levels are in the postmenopausal range. 
9.2.2 Acceptable Methods of Contraception 
Highly effective methods of birth control are defined as those that result in a low failure rate 
(< 1% per year) when used consistently and correctly. From the time of screening through 5 
months after the last dose of study drug, female subjects should practice true abstinence or use 
effective means of contraception as follows: 
• 
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; 
• 
Intrauterine device (IUD); 
• 
Intrauterine system (IUS); 
• 
Bilateral tubal ligation; 
• 
Females have been surgically sterilized for more than 6 months or postmenopausal for 
more than 1 year. Permanent sterilization is defined in Section 9.2.1. 
In addition to the above contraceptive requirements for female subjects, male partners must 
also use a contraceptive (e.g., barrier, condom or vasectomy). 
9.2.3 Pregnancy Reporting and Follow-up 
Pregnancies occurring at any time between study drug administration and up to 5 months after 
study drug administration must be reported for female subjects and female partners of male 
subjects. The investigator is responsible for informing the sponsor within 24 hours of 
knowledge of the pregnancy even if no AE has occurred per the reporting guidelines. The 
subject will be asked to provide information on the outcome of the pregnancy from the delivery 
through 6 months after birth or details of premature termination. Spontaneous miscarriage and 
congenital abnormalities will be reported as SAEs. 


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10. Statistical Methods 
10.1 10.1 Sample Size 
No formal hypothesis testing will be conducted. The number of subjects in each cohort is 
expected to provide sufficient data to allow the assessment of the safety, tolerability and PK 
profile of mavacamten in Chinese subjects. Hence approximately 8-12 subjects will be enrolled 
in Phase I to obtain adequate PK and safety data based on China regulatory consideration. 
Four cohorts are expected to enroll approximately 44 healthy adult subjects. 
 
Cohorts 1: 12 subjects (CYP2C19 UM/RM/NM) to ensure that PK data will be obtained 
for at least 10 subjects; 
 
Cohorts 2: 12 subjects (CYP2C19 UM/RM/NM) to ensure that PK data will be obtained 
for at least 10 subjects; 
 
Cohort 3: 12 subjects (CYP2C19 IM) to ensure that PK data will be obtained for at least 
10 subjects; 
 
Cohort 4: 8 subjects (CYP2C19 PM) to ensure that PK data will be obtained for at least 6 
subjects. 
10.2 Study Endpoints 
10.2.1 Pharmacokinetic Endpoints 
• 
Area under curve AUC(0-last), AUC(0-inf); 
• 
Maximum concentration (Cmax); 
• 
Time to maximum concentration (Tmax); 
• 
Elimination half-life (T1⁄2); 
• 
Apparent volume of distribution (Vd/F); 
• 
Apparent clearance (CL/F). 
10.2.2 Safety Endpoints 
• 
Vital signs; 
• 
Physical examination findings; 
• 
ECG parameters; 
• 
Laboratory data, including blood chemistry, hematology, coagulation, and urinalysis; 
• 
AE. 
10.2.3 Exploratory Endpoint 
• 
Population PK model may be assessed to investigate ethnic differences on key PK 
parameters including clearance and volume of distribution. 


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10.3 Statistical Analysis 
Before database lock, a final statistical analysis plan (SAP) for clinical data and PK analysis 
will be prepared that will contain full details of all planned analyses. An outline of the intended 
methodology is presented below. 
10.3.1 Statistical Analysis Datasets 
Two analysis populations are defined in this study. 
Pharmacokinetics Set (PKS): The pharmacokinetic (PK) analysis set consists of all subjects 
exposed to mavacamten with at least one study drug concentration value. The PKS will be used 
for PK analysis. 
Safety Analysis Set (SAS): All subjects exposed to mavacamten, regardless of the doses 
administered, will be included in the SAS. The SAS is used for safety analysis. 
10.3.2 General Principles 
Measurement data will be statistically described using the number of subjects, mean, standard 
deviation, median, min and max. Categorical variables will be summarized using counts and 
percentages. 
Pharmacokinetics parameters will be calculated using standard non-compartmental model of 
WinNonlin (version 8.2 or higher). Other statistical analyses will be performed using SAS 
(version 9.4 or higher) software. 
10.3.3 Subject Disposition 
The number and percentage of subjects who completed and discontinued the study, including 
reasons for early discontinuation, will be presented by cohort and all subjects. 
10.3.4 Demographic and Baseline Characteristics 
Demographic characteristics, baseline characteristics, medical history, and CYP2C19 genotype 
will be summarized descriptively by cohort and all subjects. 
10.3.5 Efficacy Analysis 
Not applicable. 
10.3.6 Pharmacokinetic Analysis 
All PK analyses will be conducted in the pharmacokinetics set. The plasma concentration-time 
data of mavacamten for individual subject will be listed and displayed graphically in the linear 
and semi-log scales. The plasma concentration-time data for each cohort will be summarized 
descriptively in tabular and the mean concentration-time curve will be plotted on the linear and 
semi-log scales by cohort. The PK parameter data will be listed and summarized descriptively 
in tabular format by cohort. Statistics include the number of subjects, arithmetic mean, GM, 
SD, and CV, min, median, and max. 
➢ Effect of different CYP2C19 genotypes (UM/RM/NM vs IM vs PM) 
To examine the exposure to mavacamten for subjects with the UM/RM/NM vs IM vs PM 
genotype, analysis of variance (ANOVA) model will be constructed using log-transformed 
AUC(0-last), AUC(0-inf) and Cmax. The AUC(0-last), AUC(0-inf) and Cmax will be compared between 
the cohort 1 and cohort 2 (CYP2C19 UM/RM/NM), cohort 3 (CYP2C19 IM), and cohort 4 
(CYP2C19 PM). The reference group will be cohort 1 and test groups will be cohort 2 to cohort 


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4 and the GM ratios of each parameter between all cohorts and the corresponding 2-sided 90% 
confidence intervals will be calculated. 
Further details are presented in the SAP. 
10.3.7 Ethnic Impact 
The established PopPK will be included in this trial for subsequent ethnic sensitivity analysis 
and will be reported separately. This analysis will be performed after and within the approval 
of the relevant regulatory authorities. 
10.3.8 Safety Analysis 
All safety analyses will be performed based on the Safety Set. 
The safety analysis period is defined as the time between study drug administration and the 
EOS Visit. Any AE that occurs before study drug administration or after the EOS will not be 
included in the safety analyses. Safety analyses will be based on descriptive statistics of AEs 
across cohorts and review of individual subject data such as AEs, safety laboratory data, vital 
signs, physical examination results, and ECG parameters. 
10.3.8.1 Adverse Events 
AEs will be mapped to system organ classes and preferred terms using the MedDRA. AEs will 
be monitored throughout the study to determine their severity and their potential relationship 
to the investigational drug. An AE that occurs on or after the first dose of study drug, or an AE 
that occurs prior to the first dose of study drug, worsens in severity at or after the first dose of 
study drug, will be considered a post dose-emergent AE. 
The incidence of AEs will be summarized by cohort and all subjects and by system organ class, 
preferred term, severity, and relationship to study drug. Severe and life-threatening AEs, SAEs, 
and AEs leading to study withdrawal, if any, will also be presented in data listings. 
10.3.8.2 Other Safety Analyses 
Safety laboratory tests (hematology, blood chemistry, coagulation, and urinalysis), vital signs, 
physical examinations, and ECG results will be summarized by visit time point using 
descriptive statistics based on the Safety Analysis Set. For safety laboratory data and vital signs, 
results at each visit and changes from baseline will be described. Subjects with laboratory 
and/or vital signs results outside the reference range will be listed. Abnormal physical and ECG 
findings will be listed. Concomitant medications, if any, will be summarized. 
10.3.9 PopPK Analysis 
PopPK analysis will be conducted with the data from current study LB2001-101 and other 
mavacamten studies. All analysis will be based on the actual sampling times recorded in the 
study. Additional details of the PopPK model development and analysis will be provided in a 
separate PopPK DAP and results of the PopPK analysis will be reported separately from the 
clinical study report (CSR). 
Note: PopPK analysis will be performed only after approval by relevant regulatory authorities 
and within the approved scope. 


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11. Data Collection and Management 
11.1 Data Confidentiality 
All records identifying the subject will be kept confidential and, in accordance with the 
applicable laws and/or regulations, will not be made publicly available. Subject names will not 
be supplied to the sponsor. Only the subject number will be recorded in the eCRF. If the subject 
name appears on any other document or trial materials, then that information must be redacted 
before a copy of the document is supplied to the sponsor. Trial data stored on a computer will 
be stored in accordance with local data protection laws and regulations. Subjects will be 
informed in writing that representatives of the sponsor, IRB/IEC/REB, or regulatory authorities 
may inspect their medical records to verify the information collected, and that all personal 
information made available for inspection will be handled in strictest confidence and in 
accordance with local data protection laws and regulations. 
If the results of the trial are published, the subjects' identity will remain confidential. 
The investigator will maintain a list to enable subjects' records to be identified in accordance 
with applicable laws and regulations. 
The data collection system for this study uses built-in security features to encrypt all data for 
transmission in both directions, preventing unauthorized access to confidential subject 
information. Access to the system will be controlled by a sequence of individually assigned 
user identification codes and passwords, made available only to authorized personnel who have 
completed prerequisite training. 
Either year of birth or exact date of birth (depending on local privacy regulations) will be 
recorded to establish that the subject satisfies the age requirements specified in the protocol 
and to enable appropriate age-related normal ranges to be used in assessing laboratory test 
results. 
11.2 Study Site Monitoring 
Before study initiation, the sponsor (or designated Contract Research Organization [CRO]) will 
review the protocol and eCRFs with the investigators and their staff at a study site initiation 
meeting or at an investigator's meeting. During the study, the field monitor will visit the study 
site regularly to check the completeness of subject records, the accuracy of entries in the eCRFs, 
the adherence to the protocol and to the Good clinical practice (GCP), the progress of 
enrollment, and to ensure that study drug is being stored, dispensed, and counted appropriately 
according to specifications. Key study personnel must be available to assist the field monitor 
during these visits. 
The investigator must maintain source documents for each subject in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, ECGs, and the results of any other tests or assessments. All 
information recorded in the eCRFs must be traceable to source documents in the subject's file. 
The investigator must also keep one of the original signed ICF (another signed original is given 
to the subject). 
The investigator must give the field monitor access to all relevant source documents to confirm 
their consistency with the eCRF entries. Full verification for the presence of ICF, adherence to 
the inclusion/exclusion criteria and documentation of SAEs is required in the sponsor's 
monitoring standards. Additional checks of the consistency of the source data with the eCRFs 
need to be performed according to the study specific monitoring plan. 


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11.3 Data Collection 
The designated site staff will enter the data required by the protocol into the eCRFs. The eCRFs 
have been built using fully validated secure web-enabled software. The investigator and site 
staff will not be given access to the electronic data capture (EDC) system until they have been 
trained. 
The principal investigator is responsible for assuring that the data entered into eCRF is 
complete, accurate, and that entry and updates are performed in a timely manner. 
PK samples obtained during the course of the study will be collected from the study sites and 
analyzed by a laboratory designated by the sponsor. Designated study site staff will enter the 
information required by the protocol into the appropriate eCRF and/or designated laboratory 
requisition forms. Field monitors will review the eCRFs and laboratory paper requisition forms 
for accuracy and completeness and instruct site personnel to make any required corrections or 
additions if needed. One copy of the requisition form will be forwarded to analytical laboratory 
with the respective sample(s) by the designated study site staff; and one copy will be retained 
at the study site if available. 
11.4 Database Management and Quality Control 
The sponsor (or designated CRO) will review the data entered into eCRFs by investigational 
staff for completeness and accuracy. Electronic data queries stating the nature of the problem 
and requesting clarification will be created for discrepancies and missing values and sent to the 
study site via the EDC system. Designated site staff are required to respond promptly to queries 
and to make any necessary changes to the data if needed. 
Prior medications, concomitant treatments, and post-treatment anti-cancer medications entered 
into the database will be coded using the Anatomical Therapeutic Chemical classification 
system. Medical history/current medical conditions and AEs will be coded using the MedDRA 
terminology. 
PK data will be processed centrally and the results will be sent electronically to the sponsor. 
The occurrence of any protocol deviations will be recorded. Once the data has been verified to 
be complete and accurate, the database will be declared locked and made available for data 
analysis. Appropriate sponsor authorization is required prior to making any database changes 
to locked data. 
After database lock, the investigator will receive a copy of his/her subjects' data for archiving 
at the study site. 
 
 


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11.5 Study Documentation, Record Keeping and Retention of Documents 
Each participating study site will maintain appropriate medical and research records for this 
trial, in compliance with the International Conference on Harmonization (ICH) E6 GCP, and 
regulatory and institutional requirements for the protection of confidentiality of subjects. As 
part of participating in sponsored study, each study site will permit authorized representatives 
of the sponsor(s) and regulatory agencies to examine (and when required by applicable law, to 
copy) clinical records for the purposes of quality assurance reviews, audits and evaluation of 
the study safety and progress. 
Source data are all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and revaluation of the trial. 
Examples of these source documents and data records include, but are not limited to, hospital 
records, clinical and office charts, laboratory reports, memoranda, subjects' diaries or 
evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, 
copies or transcriptions certified after verification as being accurate and complete, microfiches, 
photographic negatives, microfilm or magnetic media, and subject files and records kept at the 
pharmacy, at the laboratories, and medico-technical departments involved in the clinical trial. 
 


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12. Study Compliance and Ethical Considerations 
12.1 Regulatory and Ethical Compliance 
This clinical study will be performed in accordance with ethical principles that have their origin 
in the Declaration of Helsinki and are consistent with ICH/ GCP, applicable regulatory 
requirements. 
12.2 Informed Consent 
The ICFs used for the study must comply with the Declaration of Helsinki, ICH GCP guidelines, 
and any other local regulations. The investigator must explain the medical aspects of the study 
including the nature of the study and the treatment in such a manner that the potential subject 
is aware of potential benefits and risks. Potential subjects must be informed that participation 
is voluntary and that they may withdraw from the study at any time, without prejudice. Subjects, 
or an impartial witness, must give informed consent in writing. 
Prior to participation in any study-related procedures, subjects must sign and date an EC 
approved written ICF in a language the subject can understand. The informed consent process 
must be conducted, documented in the source document (including the date), and the form must 
be signed before the subject undergoes any study specific procedures. 
The language in the written information about the study should be as nontechnical as practical 
and should be understandable to the potential subject. Before informed consent is obtained, the 
investigator should provide the potential subject ample time and opportunity to inquire about 
the study and to decide whether or not to participate. 
All questions about the study should be answered to the satisfaction of the subject. The written 
ICF should be signed and personally dated by the subject and by the person who conducts the 
informed consent discussion. All subjects will receive a copy of his/her signed and dated ICF. 
12.3 Ethics Committee 
The term EC used in this document refers to an IRB or IEC or equivalent. The EC must review 
and, if appropriate, approve the following documents, as applicable: 
• 
Study protocol and amendment(s); 
• 
Study ICF(s) and amendment(s); 
• 
Subject recruitment procedures/documents (e.g., advertisements); 
• 
Written information to be provided to subjects; 
• 
IB and available safety information (Note: ECs do not approve IBs but are responsible 
for acknowledging receipt); 
• 
Information about payments and compensation available to subjects. 
The EC approval must be in writing, clearly identifying the study (by protocol date and/or 
version), including the documents reviewed, such as ICF, and date of the review. The 
investigator has the responsibility to provide the sponsor with the written EC approval prior to 
initiating any study-related procedures. 
The investigator also has the responsibility to inform the EC of the following according to the 
EC's policy: 


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• 
All SAEs (as described in Section 8.2); 
• 
Any new information that may affect adversely the safety of the subjects or the 
conduct of the trial; 
• 
Protocol deviations; 
• 
A synopsis of the study report upon study completion. 
Documentation of subsequent reviews and approved by EC of the study must also be 
forwarded to the sponsor if any. 
12.4 Confidentiality of Study Documents and Subject Records 
The investigator must ensure pseudonymous of the subjects by replacing names with the study-
specific subject identification number; subjects must not be identified by names in any 
documents submitted to the sponsor. The names of study subjects and all other confidential 
information are subject to medical confidentiality and the provisions of the General Data 
Protection Regulation (GDPR) and other applicable regulations or laws. Subject data may only 
be passed on in pseudonymous form beyond the study site. 
Signed ICFs and subject identification log kept at the study site to enable subject identification 
must be kept strictly confidential. 


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13. Management Procedures 
13.1 Sponsor's Responsibilities 
The sponsor reserves the right to terminate the study at any time. The sponsor and the 
investigators will assure that adequate consideration is given to the protection of the subjects' 
interests. Specific circumstances that may precipitate such termination are: 
• 
Request by Health Authority to terminate the study; 
• 
Unsatisfactory subject enrollment; 
• 
Significant or numerous deviations from study protocol requirements, such as failures 
to perform required evaluations on subjects, maintain adequate study records or 
inaccurate, incomplete, or late data recording on a recurrent basis; 
• 
The incident or severity of AEs in this or other mavacamten studies indicating 
potential health hazard caused by the study treatment. 
The sponsor will purchase clinical trial insurance in accordance with the laws of the 
country/region in which the study is conducted and provide insurance certificates to 
participating clinical sites upon request. 
13.1.1 Subject Data Confidentiality 
The processing of personal data in pursuit of this study will be limited to those data that are 
reasonably necessary to investigate the utility of the IMP used in this study. These data will be 
processed with adequate precautions to ensure confidentiality according to applicable laws. 
The sponsor ensures that the personal data are: 
• 
Collected for a specified and legitimate purpose; 
• 
Processed fairly and lawfully; 
• 
Accurate and up to date; 
Explicit consent for the processing of personal data will be obtained prospectively from the 
subject. 
The sponsor, whose responsibilities require access to personal data, agrees to keep the identity 
of subjects confidential. This confidentiality will be maintained throughout the complete data 
processing. 
Subjects will be entitled to request confirmation of the existence of personal data held by the 
sponsor and will have the right to rectify erroneous or inaccurate data up until database lock. 
13.1.2 Investigator Training 
The clinical site will have a site-specific study initiation meeting to ensure the site staff 
understands the protocol, study requirements and procedures, and data capture processes. This 
training will take place before the first subject is enrolled. Clinical site will be provided with 
information regarding GCP and regulations specific to the conduct of the clinical studies. 
Clinical site will be responsible for ensuring that new team members are adequately trained 
and the training is documented. 


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13.1.3 Ongoing Communication of Safety Information During the Study 
The sponsor will provide the investigator(s) with documentation of SUSARs from this study 
and other studies. The investigator(s) must forward this documentation to the EC as per EC's 
requirement or local regulation. 
The sponsor will also notify the investigator(s) about any other significant safety findings that 
could alter the safety profile of the IMP from what is described in the protocol and significantly 
affect the safety of subjects, affect the conduct of the study, or alter the EC's opinion about the 
continuation of the study. 
13.1.4 Study Monitoring 
The sponsor will monitor this clinical study through remote data checks and monitoring visits 
to check the adequacy of clinical site staff and facilities, and to ensure adherence to the protocol, 
study procedures, and applicable regulations by the clinical site staff. The clinical site monitor 
will also assess proper eCRF completion and source document retention. The investigator(s) 
and clinical site staff are expected to provide adequate space for monitoring visits and to 
allocate sufficient time to permit adequate review of the study's progress. The investigator(s) 
will permit study-related monitoring, audits, EC review, and regulatory inspection(s), 
providing direct access to source data/documents and study-related facilities (e.g., pharmacy, 
diagnostic laboratories). 
13.1.5 Study Auditing and Inspecting 
The sponsor may audit the study conduct, compliance with the protocol, and accuracy of the 
data in clinical site. 
The investigator/institution will permit study-related monitoring, audits, and inspections by the 
sponsor, EC, government regulatory authority, and sponsor's quality assurance personnel or its 
designees by providing direct access to source data/documents after appropriate notification to 
the sponsor. 
13.2 Investigator's Responsibilities 
13.2.1 Screening Log 
The investigator must keep a record that lists all subjects who signed an ICF and the reason for 
non-inclusion if the potential subject does not ultimately enroll. 
13.2.2 Mavacamten Accountability 
The investigator must ensure that the study drug at the study site is kept secured and accounted 
for with access limited to only those individuals authorized by the investigator. The investigator, 
his/her designee, or pharmacist must also maintain adequate records of distribution, dispensing, 
and destruction of all study drug at the end of the study. The study drug records must be readily 
available for inspection by the site monitor and/or auditor. No study drug can be destroyed or 
returned to depot until the clinical site monitor has verified the accuracy of the study drug 
records at the clinical site. 
 
 


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13.2.3 Reporting and Recording of Study Data 
Data will be captured and compiled using procedures developed by the sponsor or designee. 
EDC technology will be used for this study. Clearly record all requested study data in the eCRF 
and other forms as required. Whenever possible, record the reason for missing data in the 
source document. Only individuals who are identified in the study delegation log and who have 
received appropriate training in the EDC system may enter or correct data in the eCRF. 
Incomplete or inconsistent data in the eCRF will result in data queries that require resolution 
by the investigator or designee. Corrections to the eCRF, including the reason for the change, 
will be automatically documented through the EDC system's audit trail. 
Subject source data must be maintained as original records or a certified copy (i.e., copy of 
original information that has been verified, as indicated by a dated signature, as an exact copy 
having all of the same attributes and information as the original). The investigator and affiliated 
institution should take measures to prevent the accidental or premature destruction of 
documents. Data collected in the eCRF must match the source documents. 
An eCRF must be completed for each subject who receives at least 1 dose of IMP. All entries 
into the eCRF are ultimately the responsibility of the investigator before approving them via 
an electronic signature. The investigator is responsible for ensuring accurate, authentic, and 
complete records for each subject. 
An electronic copy of the eCRF casebooks will be sent to the clinical site for retention with 
other study documents after full completion of the study. 
13.2.4 Source Data and Documents 
The nature and location of all source documents will be identified to ensure that all sources of 
original data required to complete the eCRF are known to the company and clinical site staff. 
The source documents are to be accessible for verification by the clinical site monitor. 
Source documents should at minimum include the following information for each subject: 
• 
Subject identification and contact information (name, date of birth, sex, phone); 
• 
Documentation verifying subject eligibility (i.e., medical history, physical 
examination); 
• 
Informed consent process documentation and ICF; 
• 
Record of all visits and other contact; 
• 
Record of all AEs and other safety parameters and all event attributes; 
• 
Record of all concomitant therapy (including start/stop dates, indication for use, dose); 
• 
Date of study completion and reason for early discontinuation, if applicable. 
The author of an entry in the source documents should be identifiable as well as the date of the 
entry. Direct access to source documentation (medical records) must be allowed for the purpose 
of verifying that the data recorded in the eCRF are consistent with the source data. The 
investigator will provide certified copies of the subject's medical records in the event that 
clinical site's policy does not permit direct access to the electronic medical records. 


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13.2.5 Subject Identity Information 
To permit easy identification of the individual subject during and after the study, the 
investigator is responsible for keeping an updated log that contains the subject identification 
information. This document will be reviewed by the clinical site monitor for completeness. 
However, to ensure the subject's confidentiality, the document will be maintained at the clinical 
site and no copy will be made. 
13.2.6 Record Retention 
The sponsor will inform the investigator in writing when it is acceptable to dispose of any study 
records. To enable evaluation and/or audits from regulatory authorities or the sponsor, the 
investigator should agree to keep records, including the identity of all subjects (i.e., subject 
identification code list and all source documents), all original signed ICFs, copies of all eCRFs, 
original laboratory reports, detailed records of study medication disposition, and all essential 
documents for the conduct of a clinical study. To comply with international regulations, the 
records should be retained by the investigator for at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing application in an ICH region, or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the IMP. However, the investigator may need to 
retain these documents for a longer period if required by the local regulatory requirements or 
by an agreement with sponsor. 
13.2.7 Protocol Deviations 
Unless there is a safety concern, no protocol deviations from the study protocol or waiver of 
compliance with the study protocol will be allowed. In the event of a safety concern, the 
investigator or designee must document and explain the reason for any deviation from the 
approved protocol. The investigator may implement a deviation from, or a change to, the 
protocol to eliminate an immediate hazard to subject without prior EC approval. Immediately 
after the implemented deviation or change, the investigator must report and explain the reasons 
for the protocol deviation to the sponsor and EC as per EC's requirement. The medical monitor 
will review the protocol deviation and notify the study monitor of the response. 
13.2.8 Blood Sample Collection/Storage 
Blood samples collected as per the requirements described above will be stored at -70±10 °C 
and shipped to a central laboratory for drug concentration analysis as part of protocol 
procedures. Please refer to the relevant laboratory management manual for details of blood 
sample processing. 
 
 


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13.3 Protocol Amendments and Study Administrative Instructions 
Study procedures will not be changed without the approval of the sponsor. 
If there are any substantial changes to the study protocol, then these changes will be 
documented in a study protocol amendment and, where required, in a new version of the study 
protocol. 
The amendment should be approved by the EC and the appropriate regulatory authority(ies), 
before implementation, as appropriate. Local requirements should be followed for revised 
protocols. 
If a change to the ICF is required in a protocol amendment, the EC will need to approve the 
revised ICF before the revised form is used. 
If there are non-substantial changes such as clarification of statement or corrections to obvious 
errors/typos/inconsistencies in the protocol, or change to logistical or administrative aspects, 
then the sponsor may issue an Administrative Letter. If local regulations require any 
administrative change, it will be communicated to or approved by the EC. 
13.4 Study Management 
➢ Use of computerized systems 
This study will require the use of the following electronic data collection methods: 
• 
EDC system to capture protocol-required subject data: clinical sites will enter data 
from source documents into eCRFs for each study visit using a web-based interface. 
Study monitors and data management personnel will use this system to review data 
and generate queries and reports as needed. 
Information in the above systems will be provided to the investigator, clinical site personnel, 
and other personnel as appropriate. Measures will be taken to ensure data security and accuracy; 
including, but not limited to, user training, granting of user accounts and privileges to trained 
and authorized personnel in a role-based manner, username/password/electronic signature 
requirements enforcement, programmed and manual edit checks as outlined in data validation 
specifications, computer generated audit trails, centralized data management, and routine study 
monitoring. 
In addition, other central data management systems/databases and software may be used to 
collect and analyze study data: 
• 
Laboratory systems or proprietary systems will be used by laboratories for storing 
and/or analyzing bioanalytical laboratory data collected throughout the study; 
• 
Statistical software will be used for the statistical analysis of the study data as outlined 
in the SAP. 
➢ Study records 
The investigator and affiliated institution shall maintain the study documents and records as 
specified in "Essential Documents for the Conduct of a Clinical Trial" (ICH E6 Section 8), and 
as required by the applicable regulatory requirement(s). This includes, but is not limited to, the 
protocol, eCRFs, AE reports, subject source data (original records or certified copies), 
correspondence with health authorities and EC, ICFs, investigator's curriculum vitae, monitor 


Protocol No.: LB2001-101 
CONFIDENTIAL 
V1.0/30 Apr 2021 
 
Page 55 
visit logs, laboratory reference ranges and laboratory certification or quality control procedures, 
and laboratory director's curriculum vitae. 
The eCRF must be completed at the time of, or shortly after the subject's visit or upon receipt 
of test results. Information will be provided to clinical site staff in the proper way to complete 
the eCRF. 
A copy of each subject's eCRF will be maintained by the investigator. 


Protocol No.: LB2001-101 
CONFIDENTIAL 
V1.0/30 Apr 2021 
 
Page 56 
14. Publication Policy 
The data and results of the study will be owned by the sponsor and shall be confidential 
information of the sponsor, subject to the investigator's publication rights, all as outlined in the 
agreement between the investigator/institution and sponsor regarding the conduct of the clinical 
study (the "Clinical Study Agreement"). It is understood by the investigator that the sponsor 
may use the information developed in this study in connection with the development of the 
sponsor's proprietary IMP and, therefore, may disclose such information as necessary or useful 
to other clinical investigators or regulatory agencies. To allow for the use of the information 
derived from the study, the investigator understands that he/she has an obligation to provide 
and disclose all study results and all data developed during this study to the sponsor. 
Any publication or presentation of the results or data of this clinical study by the investigator 
may only be made in strict compliance with the provision of the Clinical Study Agreement. 
The investigator understands that it is not the sponsor's intention to prevent publication of the 
data generated in the study; rather, the sponsor reserves the right to control the form and timing 
of such publication for commercial reasons and desires to confirm the scientific accuracy of 
such information prior to such publication or presentation. 


Protocol No.: LB2001-101 
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V1.0/30 Apr 2021 
 
Page 57 
15. References 
[1] Frey N, Luedde M, and Katus HA. Mechanisms of disease: hypertrophic cardiomyopathy. 
Nat Rev Cardiol. 2011:9: 91-100. 
[2] Hershberger RE, Cowan J, Morales A, Siegfried JD. Progress with genetic 
cardiomyopathies: screening, counseling, and testing in dilated, hypertrophic, and 
arrhythmogenic right ventricular dysplasia/cardiomyopathy. Circ Heart Fail. 2009;2: 253-
61. 
[3] Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA Guideline for the diagnosis and 
treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology 
Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll 
Cardiol. 2011;58: e212-60. 
[4] Maron MS. Clinical utility of cardiovascular magnetic resonance in hypertrophic 
cardiomyopathy. J Cardiovasc Magn Reson 2012, 1: 13. 
[5] Alfares AA, Kelly MA, McDermott G, Funke BH, Lebo MS, Baxter SB, Shen J, et al. 
Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: 
expanded panels offer limited additional sensitivity, Genet Med. 2015;17: 880-8. 
[6] Chuan P, Sivaramakrishnan S, Ashely EA, Spudich JA. Cell-intrinsic functional effects of 
the α-cardiac myosin Arg-403-Gln mutation in familial hypertrophic cardiomyopathy. 
Biophys J. 2012;102: 2782-90. 
[7] Sommese RF, Sung J, Nag S, et al. Molecular consequences of the R453C hypertrophic 
cardiomyopathy mutation on human beta-cardiac myosin motor function. Proc Natl Acad 
Sci USA. 2013; 110:12607-12. 
[8] Sung J, Choe E, Elting M, et al. Single molecule studies of recombinant human α- and β-
cardiac myosin to elucidate molecular mechanism of familial hypertrophic and dilated 
cardiomyopathies. Biophysical J. 2012;102: 613a-4a. 
[9] Maron, MS, Rowin EJ, Olivotto I, Casey SA, Arretini A, Tomberli B, et al. Contemporary 
Natural History and Management of Nonobstructive Hypertrophic Cardiomyopathy, J Am 
Coll Cardiol. 2016;67: 1399-409. 
[10] Husser DL, Ueberham J, Jacob D, Heuer S, Riedel-Heller J, Walker G, et al. Prevalence 
of clinically apparent hypertrophic cardiomyopathy in Germany-An analysis of over 5 
million patients. PLoS One. 2018:13: e0196612. 
[11] Pujades-Rodriguez, M, Guttmann OP, Gonzalez-Izquierdo A, Duyx B, O'Mahony C, 
Elliott P, et al. Identifying unmet clinical need in hypertrophic cardiomyopathy using 
national electronic health records. PLoS One. 2018;13: e0191214. 
[12] Moon I, Lee SY, Kim HK, Han KD, Kwak S, Kim M, Lee HJ et al. Trends of the 
prevalence and incidence of hypertrophic cardiomyopathy in Korea: A nationwide 
population-based cohort study. PLoS One. 2020;15: e0227012. 
[13] Zou Yubao, Song Lei, Wang Zhimin, Ma Aiqun, Liu Tangwei, Gu Huimin, et al. 
Prevalence of idiopathic hypertrophic cardiomyopathy in China: A population-based 
echocardiographic analysis of 8080 adults. AM J Med. 2004;116:14-8. 
[14] Maron MS, Olivotto I, Zenovich AG, Link MS, Pandian NG, Kuvin JT, et al., 
Hypertrophic cardiomyopathy is predominantly a disease of left ventricular outflow tract 


Protocol No.: LB2001-101 
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V1.0/30 Apr 2021 
 
Page 58 
obstruction. Circulation. 2006; 114:2232-2239. 
[15] Sherrid MV, Gunsburg DZ, Moldenhauer S, Pearle G. Systolic anterior motion begins at 
low left ventricular outflow tract velocity in obstructive hypertrophic cardiomyopathy. J 
Am Coll Cardiol. 2000;36: 1344-54. 
[16] Maron MS, Olivotto I, Betocchi S, Casey SA, Lesser JR, Losi MA, Cecchi F, Maron BJ. 
Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic 
cardiomyopathy. N Engl J Med. 2003;348: 295-303. 
[17] Elliott PM, Gimeno JR, Thaman R, Shah J, Ward D, Dickie S, et al. Historical trends in 
reported survival rates in patients with hypertrophic cardiomyopathy. Heart. 2006;92: 785-
91. 
[18] Autore, CP, Bernabo P, Barilla CS, Bruzzi P, Spirito P. The prognostic importance of left 
ventricular outflow obstruction in hypertrophic cardiomyopathy varies in relation to the 
severity of symptoms. J Am Coll Cardiol. 2005;45;1076-80. 
[19] Ho CY, Sweitzer NK, McDonough B, Maron BJ, Casey SA, Seidman JG, et al. 
Assessment of diastolic function with Doppler tissue imaging to predict genotype in 
preclinical hypertrophic cardiomyopathy. Circulation. 2002;105: 2992-7. 
[20] Ho CY, Day SM, Ashley EA, Michels M, Pereira AC, Jacoby D, et al. Genotype and 
Lifetime Burden of Disease in Hypertrophic Cardiomyopathy: Insights from the 
Sarcomeric Human Cardiomyopathy Registry (SHaRe). Circulation. 2018;138: 1387-98. 
[21] Elliott PM, Anastasakis A, Borger MA, et al. 2014 ESC Guidelines on diagnosis and 
management of hypertrophic cardiomyopathy. Eur Heart J. 2014;35(39):2733-2779. 
[22] Heart Failure Committee of Chinese Medical Doctors Association, et al. Chinese 
guidelines for the management of hypertrophic cardiomyopathy. Chin J Heart Fail & 
Cardiomyopathy.2017; 1(2): 65-86. 
[23] Kim LK, Swaminathan RV, Looser P, Minutello RM, Wong SC, Bergman G, et al. 
Hospital Volume Outcomes After Septal Myectomy and Alcohol Septal Ablation for 
Treatment of Obstructive Hypertrophic Cardiomyopathy: US Nationwide Inpatient 
Database, 2003-2011. JAMA Cardiol. 2016;1: 324-32. 
[24] Yelena I, James A, Jianan Z, et al. CYP2C19 Allele Frequencies in Over 2.2 Million 
Direct‐to‐Consumer Genetics Research Subjects and the Potential Implication for 
Prescriptions in a Large Health System, Clin Transl Sci. 2020;13, 1298-306. 


Protocol No.: LB2001-101 
CONFIDENTIAL 
V1.0/30 Apr 2021 
 
Page 59 
Appendix 1 Laboratory Tests 
The following safety laboratory parameters will be measured by the local laboratory: 
Hematology 
Coagulation 
function 
Blood chemistry 
Urinalysisa 
• 
White blood cell count 
including differential 
• 
Red blood cell count 
• 
Hemoglobin 
• 
Haematocrit 
• 
Platelet count 
 
 
• 
PT 
• 
INR 
• 
APTT 
• 
TT 
• 
FIB 
• 
Sodium 
• 
Potassium 
• 
Chloride 
• 
Calcium 
• 
Magnesium 
• 
Urea nitrogen 
• 
Creatinine 
• 
Uric acid 
• 
ALP 
• 
ALT 
• 
AST 
• 
Total bilirubin 
• 
Direct bilirubin 
• 
Total protein 
• 
Albumin 
• 
CK 
• 
Glucose 
• 
Specific 
gravity 
urine 
• 
Urine pH 
• 
Protein urine 
• 
Urine glucose 
• 
Urine 
leukocyte 
esterase 
• 
Urine ketone body 
• 
Red 
blood 
cells 
urine 
• 
White blood cells 
urine 
Abbreviations: ALP = alkaline phosphatase; ALT = alanine aminotransferase; APTT = activated partial 
thromboplastin time; AST = aspartate aminotransferase; CK = creatine kinase; FIB = fibrinogen; FSH = 
follicle stimulating hormone; HIV = human immunodeficiency virus; INR = international normalized ratio; 
PT = prothrombin time; TT = thrombin time. 
 
aUrine microscopy and dipstick will be performed. 
Safety laboratory assessments (hematology, blood chemistry, coagulation test, urinalysis) has 
no need to be repeated on Day -1 if latest results are within 7 days. Details are provided in 
Table 1. 
The following non-safety laboratory parameters will be measured at screening: 
• 
Hepatitis virus test (HBV and HCV): HBV antigen, HCV antibody; 
• 
HIV test: HIV antibody; 
• 
FSH (post-menopausal females only); 
• 
Pregnancy test (β-hCG) (all women of childbearing potential); 
• 
Alcohol or drug abuse test. 


Protocol No.: LB2001-101 
CONFIDENTIAL 
V1.0/30 Apr 2021 
 
Page 60 
Sponsor’s Signature Page 
Authorization of the Sponsor 
This protocol (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) has been reviewed and approved by representatives of Shanghai LianBio 
Development Co., Ltd. 
 
 
Printed Name 
Signature 
 
 
Title 
Date (dd-mm-yyyy) 
  
 
 


Protocol No.: LB2001-101 
CONFIDENTIAL 
V1.0/30 Apr 2021 
 
Page 61 
Investigator's Signature Page 
I have read and understood the contents of the clinical protocol (An Open-Label, Parallel-
Group, Single-Center Phase 1 Clinical Trial to Evaluate the Pharmacokinetics of a Single Oral 
Dose of Mavacamten in Healthy Adult Chinese Subjects). 
I have reviewed this protocol and agree to implement this protocol in compliance with the 
ethical principles deriving from the Declaration of Helsinki, GCP of ICH, and the requirements 
of any regulatory authority and/or IRB/IEC. 
I agree to allow the sponsor's representatives and relevant regulatory authorities to access my 
subject study records so that they can verify the data I or my designee have entered into the 
CRF. I understand the responsibilities as a Principal Investigator. 
I understand that the sponsor may decide to suspend or prematurely terminate this study at any 
time for any reasons; such decisions will be communicated to me in writing. Conversely, if a 
decision is made to withdraw my site from this study, I will immediately notify the sponsor in 
writing. 
 
 
Printed Name 
Signature 
 
 
Title 
Date (dd-mm- yyyy) 
 

SAP_001.pdf: 
Parexel International 
Shanghai LianBio Development Co., Ltd. 
LB2001-101 
Statistical Analysis Plan 
TP-GDO-WW-133-02 
CONFIDENTIAL 
Project Document Version No. 2.0 
Effective Date:  14 May 21 
Project Document Effective Date: <Date of last signature> 
Related to:  SOP-GDO-WW-019 
Page 1 of 33 
Parexel International 
Shanghai LianBio Development Co., Ltd. 
LB2001-101
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 
Statistical Analysis Plan 
Version: <2.0> 
Parexel Project Number: 256888


Parexel International 
Shanghai LianBio Development Co., Ltd. 
LB2001-101 
Statistical Analysis Plan 
TP-GDO-WW-133-02 
CONFIDENTIAL 
Project Document Version No. 2.0 
Effective Date:  14 May 21 
Project Document Effective Date: <Date of last signature> 
Related to:  SOP-GDO-WW-019 
Page 2 of 33 
SPONSOR SIGNATURE PAGE 
Approved by:  
_________________________ 
_______________ 
Tuo Zhang 
 
Date 
Senior Manager
Physician
Shanghai LianBio Development Co., Ltd.
Approved by:  
_________________________ 
_______________ 
Mina Hsu 
Date 
Senior Manager, Clinical Pharmacology
Shanghai LianBio Development Co., Ltd.
Approved by:  
_________________________ 
_______________ 
Yupeng Li 
 
Date 
Associate Manager, Biostatistics
Shanghai LianBio Development Co., Ltd.


Parexel International 
Shanghai LianBio Development Co., Ltd. 
LB2001-101 
Statistical Analysis Plan 
TP-GDO-WW-133-02 
CONFIDENTIAL 
Project Document Version No. 2.0 
Effective Date:  14 May 21 
Project Document Effective Date: <Date of last signature> 
Related to:  SOP-GDO-WW-019 
Page 3 of 33 
Parexel SIGNATURE PAGE 
Signatures below confirm that the Statistical Analysis Plan was developed in accordance with SOP-
GDO-WW-019 and that it is approved for release. 
This document has been approved and signed electronically on the final page by the 
following: 
Signatory 
Author 
[Alex Liu] 
Project Role: Biostatistics Lead/Biostatistician   
Signatory 
Author 
[Novakovic Ana] 
Project Role: QCD Scientist   
Signatory 
Reviewer 
[Lifang Zhang] 
Project Role: Biostatistical Reviewer/Principle Biostatistician   


Parexel International 
Shanghai LianBio Development Co., Ltd. 
LB2001-101 
Statistical Analysis Plan 
TP-GDO-WW-133-02 
CONFIDENTIAL 
Project Document Version No. 2.0 
Effective Date:  14 May 21 
Project Document Effective Date: <Date of last signature> 
Related to:  SOP-GDO-WW-019 
Page 4 of 33 
TABLE OF CONTENTS 
1
INTRODUCTION ...................................................................................................................... 9
2
STUDY OBJECTIVES .............................................................................................................. 9
2.1 Primary Objective ........................................................................................................................................... 9
2.2 Secondary Objective ...................................................................................................................................... 9
2.3 Exploratory Objective ................................................................................................................................... 9
3
INVESTIGATIONAL PLAN.................................................................................................... 9
3.1 Overall Study Design .................................................................................................................................... 9
3.2 Study Period ................................................................................................................................................... 10
3.3 Endpoints and Associated Variables ....................................................................................................... 11
3.3.1 Pharmacokinetic Variables ............................................................................................ 11 
3.3.2 Safety Variables ............................................................................................................. 13 
3.3.3 Exploratory Variables .................................................................................................... 15 
4
STATISTICAL METHODS ................................................................................................... 15
4.1 Data Quality Assurance .............................................................................................................................. 15
4.2 General Presentation Considerations ...................................................................................................... 15
4.3 Software ........................................................................................................................................................... 15
4.4 Study Subjects ............................................................................................................................................... 16
4.4.1 Analysis Sets .................................................................................................................. 16 
4.4.2 Disposition of Subjects .................................................................................................. 16 
4.4.3 Protocol Deviations ........................................................................................................ 16 
4.5 Demographics and Baseline Characteristics ......................................................................................... 17
4.6 Medical History and Concomitant Illnesses ......................................................................................... 17
4.7 Prior and Concomitant Medications ........................................................................................................ 17
4.8 Pharmacokinetics .......................................................................................................................................... 17
4.8.1 Pharmacokinetic Concentrations.................................................................................... 17 
4.8.2 Handling of Concentration Values Below the Limit of Quantification (BLQ) ............. 18 
4.8.3 Pharmacokinetic Parameters .......................................................................................... 19 
4.8.4 Pharmacokinetic Analysis .............................................................................................. 22 
4.8.5 Population PK (PopPK) Analysis: ................................................................................. 22 
4.9 Safety Evaluation .......................................................................................................................................... 22
4.9.1 Adverse Events .............................................................................................................. 22 
4.9.2 Deaths, Serious Adverse Events, and Other Significant Adverse Events ...................... 23 
4.9.3 Clinical Laboratory Evaluation ...................................................................................... 24 
4.9.4 Vital Signs, Physical Findings and Other Observations Related to Safety .................... 24 
4.10 Handling of Dropouts or Missing Data .................................................................................................. 25
4.11 Planned Interim Analysis ........................................................................................................................... 25
4.12 Determination of Sample Size .................................................................................................................. 25
5
REFERENCES ......................................................................................................................... 25
6
APPENDICES .......................................................................................................................... 26
6.1 Schedule of Assessments ....................................................................................................... 26 
6.2 Schedule of PK Sampling .......................................................................................................................... 27


Parexel International 
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LB2001-101 
Statistical Analysis Plan 
TP-GDO-WW-133-02 
CONFIDENTIAL 
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Effective Date:  14 May 21 
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Related to:  SOP-GDO-WW-019 
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6.3 Imputation Rules for Partial Dates .......................................................................................................... 28


Parexel International 
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Page 6 of 33 
REVISION HISTORY 
Version No. 
Effective Date 
Summary of Change(s) 
2.0 
28-Feb-2022 
1.
Pharmacokinetic parameters: DNCmax, DNAUC 
2. Definition of PKS was updated to be: The pharmacokinetic 
(PK) analysis set consists of all subjects exposed to 
mavacamten with at least one plasma drug concentration 
result and without serious protocol violations affecting the 
PK parameter results.
3. Figure 1: Individual profiles for mavacamten: Plasma 
Concentration Time Data – (Linear Scale and Semi-
Logarithmic Scale) (PKS) was revised to be Figure 1: 
Individual overlaid profiles for mavacamten (0-24h): Plasma 
Concentration Time Data – (Linear Scale and Semi-
Logarithmic Scale) (PKS) 
4. Figure 3: Mean (± SD) mavacamten per cohort: Plasma 
Concentration Time Data – (Linear Scale and Semi-
Logarithmic Scale) (PKS) was revised to be Figure 3: Mean 
(± SD) mavacamten overlaid profiles per cohort (0-24h): 
Plasma Concentration Time Data – (Linear Scale and Semi-
Logarithmic Scale) (PKS) 
5. Figure 4: mavacamten Mean (± SD) overlaid profiles per 
cohort: Plasma Concentration Time Data – (Linear Scale 
and Semi-Logarithmic Scale) (PKS) was added. 
6. Addition: 
Figure 7: Dose-Normalized Box plots of Cmax (PKS) 
Figure 8: Dose-Normalized Box plots of AUC0-last (PKS) 
Figure 9: Dose-Normalized Box plots of AUC0-inf (PKS) 


Parexel International 
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LB2001-101 
Statistical Analysis Plan 
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CONFIDENTIAL 
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Related to:  SOP-GDO-WW-019 
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LIST OF ABBREVIATIONS 
Abbreviation / Acronym 
Definition / Expansion 
AE 
AESI 
Adverse Event 
Adverse Event of Special Interest 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
APTT 
Activated Partial Thromboplastin Time 
AST 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
AUC 
Area Under the Concentration-time Curve 
AUC(0-inf)
AUC from Time Zero Extrapolated to Infinity 
AUC(0-t)
AUC from Time Zero to the Last Quantifiable Concentration 
BLQ 
Below the Lower Limit of Quantification 
BMI 
Body Mass Index 
BP 
Blood Pressure 
Bpm 
Beats Per Minute 
CL/F 
Apparent Clearance 
Cmax
Maximum Plasma Drug Concentration 
CRF 
Case Report Form 
CS 
Clinically Significant 
CSR 
Clinical Study Report 
CSP 
Clinical Study Protocol 
CV 
Coefficient of Variation 
CYP 
Cytochrome P450  
DBP 
Diastolic Blood Pressure 
DRM 
Data Review Meeting 
ECG 
Electrocardiogram 
EOS 
End-of-study 
gCV% 
Geometric Coefficient of Variation 
GM 
Geometric mean 
HIV 
Human Immunodeficiency Virus 


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Statistical Analysis Plan 
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Related to:  SOP-GDO-WW-019 
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Abbreviation / Acronym 
Definition / Expansion 
HR 
Heart Rate 
ICF 
Informed Consent Form 
IM 
Intermediate Metabolizer 
INR 
International Normalized Ratio 
LLOQ 
Lower Limit of Quantification 
MedDRA 
Medical Dictionary for Regulatory Activities 
NA 
Not Available 
NCS 
Not Clinically Significant 
NK 
Not Known 
NM 
Normal Metabolizer 
PK 
Pharmacokinetic 
PKS 
Pharmacokinetic set 
PM 
Poor Metabolizers 
PT 
Preferred Term 
PT 
Prothrombin Time 
QTc 
Corrected QT Interval 
QTcF 
QT Corrected Using Fridericia’s Formula 
RBC 
Red Blood Cell 
RM 
Rapid metabolizer 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SBP 
Systolic Blood Pressure 
SD 
Standard Deviation 
SOC 
System Organ Class 
t½
Apparent Terminal Elimination Half-life  
tmax
Time Corresponding to Occurrence of Cmax
UM 
Ultra-rapid Metabolizer 
Vz/F 
Apparent Volume of Distribution During Terminal Phase 
WHO-DD 
World Health Organisation - Drug Dictionary 
z
Terminal Elimination Rate Constant 


Parexel International 
Shanghai LianBio Development Co., Ltd. 
LB2001-101 
Statistical Analysis Plan 
TP-GDO-WW-133-02 
CONFIDENTIAL 
Project Document Version No. 2.0 
Effective Date:  14 May 21 
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Related to:  SOP-GDO-WW-019 
Page 9 of 33 
1
INTRODUCTION 
This Statistical Analysis Plan (SAP) describes all planned analyses for the Clinical Study Report 
(CSR) of Study  LB2001-101,  An Open label, Single-center Study on Pharmacokinetics of Single-
Dose Mavacamten in Chinese Healthy Adults. 
The content of this SAP is based on following study documents: 
Study Protocol, Version 1.0 (Apr 30, 2021) 
2
STUDY OBJECTIVES 
2.1
Primary Objective 
To evaluate the pharmacokinetics (PK) of a single oral dose of mavacamten in healthy adult 
Chinese subjects with different CYP2C19 genotypes. 
2.2
Secondary Objective 
To evaluate the safety and tolerability of a single oral dose of mavacamten in healthy adult 
Chinese subjects with different CYP2C19 genotypes. 
2.3
Exploratory Objective 
To evaluate the population PK. 
3
INVESTIGATIONAL PLAN 
3.1
Overall Study Design  
This is an open-label, parallel-group, single-center Phase 1 clinical trial. Healthy adult Chinese 
subjects with different CYP2C19 genotypes (Cohort 1 and Cohort 2: CYP2C19 ultra-rapid 
metabolizer (UM), rapid metabolizer (RM), or normal metabolizer (NM); Cohort 3: CYP2C19 
intermediate metabolizer (IM); Cohort 4: CYP2C19 poor metabolizer (PM)) will be included and 
administered with a single oral dose of mavacamten to evaluate its PK profile. 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. 


Parexel International 
Shanghai LianBio Development Co., Ltd. 
LB2001-101 
Statistical Analysis Plan 
TP-GDO-WW-133-02 
CONFIDENTIAL 
Project Document Version No. 2.0 
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Project Document Effective Date: <Date of last signature> 
Related to:  SOP-GDO-WW-019 
Page 10 of 33 
Abbreviations: CYP = Cytochrome P450; EOS = end of study; IM = intermediate metabolizers; NM = normal 
metabolizer; PM = poor metabolizer; RM = rapid metabolizer; UM = ultra-rapid metabolizer. 
Approximately 44 healthy adult Chinese subjects with different CYP2C19 genotypes will be 
enrolled in this clinical trial. This is a single-center study. Subjects will be divided into 4 cohorts. 
Cohorts 1 and 2: 12 healthy adult Chinese subjects to ensure that data will be obtained for at 
least 10 subjects; with their CYP2C19 genotypes being: 
•
CYP2C19 UM: *17/*17 or 
•
CYP2C19 RM: *1/*17 or 
•
CYP2C19 NM: *1/*1; 
Cohort 3: 12 healthy adult Chinese subjects to ensure that data will be obtained for at least 10 
subjects; with their CYP2C19 genotypes being: 
•
CYP2C19 IM: *1/*2 or *1/*3; 
Cohort 4: 8 healthy adult Chinese subjects to ensure that data will be obtained for at least 6 
subjects; with their CYP2C19 genotypes being: 
•
CYP2C19 PM: *2/*2, *3/*3, or *2/*3. 
3.2
Study Period  
The overall study period for each subject is up to 16 weeks. The study periods are as follow: 
•
Pre-screening period: Day -43 to Day -15, up to 28 days; 
•
Screening period: Day-14 to Day -2, up to 13 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. 


Parexel International 
Shanghai LianBio Development Co., Ltd. 
LB2001-101 
Statistical Analysis Plan 
TP-GDO-WW-133-02 
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Project Document Version No. 2.0 
Effective Date:  14 May 21 
Project Document Effective Date: <Date of last signature> 
Related to:  SOP-GDO-WW-019 
Page 11 of 33 
3.3
Endpoints and Associated Variables 
3.3.1
Pharmacokinetic Variables 
Pharmacokinetic concentration data will be obtained at the time points described in schedule of 
assessment (Table 1).
The following PK parameters will be determined for mavacamten in plasma following single dose 
administration: 


Parexel International 
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Statistical Analysis Plan 
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Table 3-1 
Pharmacokinetic Parameters after Single Dose Administration 
Parameter 
WNL Name 
CDISC Name 
Definition 
Cmax
Cmax 
CMAX 
Maximum Plasma Drug 
Concentration 
tmax
Tmax 
TMAX 
Time corresponding to 
occurrence of Cmax
t½
HL_Lambda_z 
LAMZHL 
Apparent terminal 
elimination half-life 
AUC(0-last) 
AUClast 
AUCLST 
AUC from time zero to the 
last quantifiable 
concentration 
AUC(0-inf) 
AUCINF_obs 
AUCIFO 
AUC from time zero 
extrapolated to infinity 
%AUCex
AUC_%Extrap_obs 
AUCPEO 
Percentage of AUC(0-inf) 
obtained by extrapolation 
tlast
CL/F 
Cl_F_obs 
CLFO 
Apparent clearance 
following oral 
administration 
Vz/F 
Vz_F_obs 
VZFO 
Apparent volume of 
distribution during 
terminal phase 
DNCmax
DNCmax
DNCMAX
Dose normalized 
Maximum 
Plasma 
Drug 
Concentrati
on 
DNAUC(0-last)
DNAUClast
DNAUCLST
Dose normalized AUC 
from time 
zero to the 
last 
quantifiable 
concentratio
n 


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Parameter 
WNL Name 
CDISC Name 
Definition 
DNAUC(0-inf)
DNAUCINF_obs
DNAUCIFO
Dose normalized AUC 
from time 
zero 
extrapolated 
to infinity 
3.3.2
Safety Variables 
Safety will be assessed throughout the study, or at the time points described schedule of assessment 
(Table 1). 
Adverse events (AEs) 
Adverse Event (AE) 
An AE is any untoward medical occurrence in a subject after receiving the investigational product 
and does not necessarily have a clear causal relationship with the investigational drug. An AE can 
therefore be any unfavorable and unintended sign (e.g., tachycardia, enlarged liver, clinically 
significant or abnormal laboratory result), subject-reported symptom (e.g., nausea, chest pain), or 
evidence of any disease activity temporally associated with the use of a study medication, whether 
or not related to the use of the study medication. 
Drug Taken Period Adverse Event  
A drug taken period AE will be defined as any AE that emerge during treatment (i.e., AE which 
started after study drug administration or pre-existed that worsened in severity after study drug 
administration). 
Adverse Events of Special Interest (AESI) 
Symptomatic overdose, outcomes of a pregnancy, and LVEF
30% as determined by local site are 
considered as Adverse Events of Special Interests (AESIs).  
Serious Adverse Event (SAE) 
A SAE is an AE that fulfills one or more of the following criteria in the opinion of the investigator 
or sponsor:  
•
Results in death; 
•
is immediately life-threatening (places the subject at immediate risk of death from the 
event as it occurred); 
•
Requires subject hospitalization or prolongation of existing hospitalization; 
•
Resulting in persistent or significant disability or incapability or substantial disruption of 
the ability to conduct normal life functions. 
•
Results in a congenital abnormality or birth defect. 
Is an important medical event that may not result in death, be life-threatening, or require 
hospitalization, but may be considered a SAE when, based upon appropriate medical judgment, it 
may require medical or surgical intervention to prevent one of the outcomes listed above. 


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Physical examination findings: 
Complete physical examination: general appearance, skin, head and neck, mouth, lymph nodes, 
thyroid, abdomen, and musculoskeletal, cardiovascular, neurological, and respiratory systems. 
Brief physical examination: cardiovascular and respiratory examinations. 
ECG parameters: HR, rhythm, PR interval, QRS interval, QT interval, P wave, QRS complex, 
T wave morphology, ST segment displacement. 
Vital signs: Systolic  blood pressure (SBP) [mmHg], Diastolic blood pressure (DBP) [mmHg] 
Respiratory rate (bpm), Heart rate (bpm), temperature [°C]. 
Clinical laboratory tests: 
Table 3-2 
Laboratory Tests 
Hematology 
Coagulation 
function 
Blood chemistry 
Urinalysisa
•
White 
blood 
cell 
count 
including 
differential 
•
Red blood cell count 
•
Hemoglobin 
•
Haematocrit 
•
Platelet count 
•
PT 
•
INR 
•
APTT 
•
TT 
•
FIB 
•
Sodium 
•
Potassium 
•
Chloride 
•
Calcium 
•
Magnesium 
•
Urea nitrogen 
•
Creatinine 
•
Uric acid 
•
ALP 
•
ALT 
•
AST 
•
Total bilirubin 
•
Direct 
bilirubin 
•
Total protein 
•
Albumin 
•
CK 
•
Glucose
•
Specific 
gravity 
urine 
•
Urine pH 
•
Protein urine 
•
Urine glucose 
•
Urine 
leukocyte 
esterase 
•
Urine 
ketone 
body 
•
Red blood cells 
urine 
•
White blood cells 
urine 
Abbreviations: ALP = alkaline phosphatase; ALT = alanine aminotransferase; APTT = activated partial 
thromboplastin time; AST = aspartate aminotransferase; CK = creatine kinase; FIB = fibrinogen; FSH = follicle 
stimulating hormone; HIV = human immunodeficiency virus; INR = international normalized ratio; PT = 
prothrombin time; SAE = serious AE; TT = thrombin time.
aUrine microscopy will be performed if there is a significant abnormality in the dipstick. 
Safety laboratory assessments (hematology, blood chemistry, coagulation test, urinalysis) has no 
need to be repeated on Day -1 if latest results are within 7 days. 
The following non-safety laboratory parameters will be measured at screening: 
• Hepatitis virus test (HBV and HCV): HBV antigen, HCV antibody; 
• HIV test: HIV antibody 
• FSH (post-menopausal females only); 


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• Alcohol or drug abuse test 
3.3.3
Exploratory Variables 
Population PK model may be assessed to investigate ethnic differences on key PK parameters 
including clearance and volume of distribution. 
4
STATISTICAL METHODS 
4.1
Data Quality Assurance 
All tables, figures and data listings to be included in the report will be independently checked for 
consistency, integrity and in accordance with standard Parexel procedures. 
4.2
General Presentation Considerations 
 ‘Baseline’ is defined as the last available pre-treatment assessment. ‘End of Study’ is defined as the 
last available post-treatment assessment.   
Continuous data will be summarized in terms of the mean, standard deviation (SD), upper quartile, 
median, lower quartile, minimum, maximum and number of observations, unless otherwise stated.  
The minimum and maximum will be reported to the same number of decimal places as the raw data 
recorded in the database. The mean, median, lower quartile and upper quartile will be reported to 
one more decimal place than the raw data recorded in the database. The SD will be reported to two 
more decimal places than the raw data recorded in the database. In general, the maximum number 
of decimal places reported shall be four for any summary statistic. 
Categorical data will be summarized in terms of the number of subjects providing data at the 
relevant time point (n), frequency counts and percentages.  
Percentages will be presented to one decimal place. Percentages will not be presented for zero 
counts.  Percentages will be calculated using n as the denominator.  
Changes from baseline in categorical data will be summarized using shift tables where appropriate. 
P-values greater than or equal to 0.001, in general, will be presented to three decimal places. P-
values less than 0.001 will be presented as “<0.001”. 
Confidence intervals will be presented to one more decimal place than the raw data. 
4.3
Software 
All report outputs will be produced using SAS® version [9.4] or a later version in a secure and 
validated environment.  
PK analyses will be produced using Phoenix® WinNonLin (WNL) version [8.2] or a later version in 
a secure and validated environment.  
All report outputs will be provided to the Sponsor in RTF format and can be combined to a whole 
PDF file.   


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4.4
Study Subjects 
4.4.1
Analysis Sets 
Enrolled Analysis Set (ENR)
All subjects who have signed informed consent without screening 
failure. 
Pharmacokinetics Set (PKS): The pharmacokinetic (PK) analysis set consists of all subjects exposed 
to mavacamten with at least one plasma drug concentration result and without serious protocol 
violations affecting the PK parameter results. The PKS will be used for PK analysis. 
Safety Analysis Set (SAS): All subjects exposed to mavacamten, regardless of the doses 
administered, will be included in the SAS. The SAS is used for safety analysis. 
A summary table with the number of subjects in each of the analysis set will be provided and this 
table will be displayed by cohort and overall, for ENR. A listing of subjects excluded from analysis 
sets will also be provided including reason of exclusion for ENR. 
A by-subject listing of analysis set details will be provided. This listing will be presented by cohort 
and include subject identifier, inclusion/exclusion flag and reason for exclusion from each analysis 
set. All subjects screened will appear on this listing.  
4.4.2
Disposition of Subjects 
Screening failures (i.e., subjects who signed the ICF but do not receive study treatment) and the 
associated reasons for failure will be tabulated overall. 
A summary of study treatment status will be provided for the ENR. This display will show the 
number and percentage of subjects who have completed the study or have discontinued study 
treatment and a summary of the primary reasons for discontinuation of study treatment.  
A -by subject listing of study treatment discontinuation will be presented for the ENR. The listing 
will include reasons for discontinuation of study treatment.  
4.4.3
Protocol Deviations 
All protocol deviations are predefined in the separate document, Protocol Deviation Specification. 
4.4.3.1
Protocol Deviations with Non-PK Implications 
The defined protocol deviations will be collected during the study period by site monitor/clinical 
team and programming team. All deviations related to study inclusion or exclusion criteria, conduct 
of the study, subject management or subject assessment, and handling of the subject’s rights will be 
described.  
4.4.3.2
Protocol Deviations with PK Implications 
Protocol deviations that may potentially impact PK parameter derivation include, but are not limited 
to: 
•
Emetic episode in case of orally administered study drug 
•
Missed PK samples that impact estimation of PK parameter(s) 
•
Concomitant medications not authorized by protocol 


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•
PK samples obtained out of allowance window that may impact the estimation of PK 
parameter(s) 
Protocol deviations (mentioned in Sections 4.4.3.1 and 4.4.3.2) and analysis sets will be reviewed in 
the data review meeting (DRM) to decide analyses sets and to decide if special subject’s data will 
be excluded from certain analyses. Decisions regarding the exclusion of subjects and/or data from 
analyses will be made prior to database lock and will be documented and approved. 
A -by subject listing of major and minor protocol deviations will be provided including subject 
identifier; leading to exclusion from specific analysis sets; and protocol deviation classification, and 
protocol deviation description. 
4.5
Demographics and Baseline Characteristics 
The demographic characteristics (age, gender, ethnic, height, body weight, body mass index [BMI]), 
CYP2C19 genotypes will be summarized by cohort and overall and listed by subject for the SAS.  
4.6
Medical History and Concomitant Illnesses 
All medical history and concomitant illnesses will be coded to System Organ Class (SOC) and 
Preferred Term (PT) using the MedDRA version 24.0 or later version. All medical history and 
concomitant illnesses will be summarized by SOC and PT by cohort and overall for the SAS.  
A by-subject listing of medical history and concomitant illnesses will be also provided. 
4.7
Prior and Concomitant Medications 
Medications will be considered as prior if they with a stop date prior to administration of the study 
drug.  
Medications will be considered as concomitant if they are stopped on or after administration of the 
study drug.  
All concomitant medications will be coded to Anatomical Therapeutic Chemical (ATC) 
classification and PT using the World Health Organization Drug Dictionary (WHO-DD) SEP 2020 
or later version. All concomitant medications will be summarized by ATC and PT for the SAS. 
A by-subject listing will be provided with relevant information for prior and concomitant 
medications. 
4.8
Pharmacokinetics 
4.8.1
Pharmacokinetic Concentrations 
Concentration Listings: 
Pharmacokinetic concentration data for mavacamten, will be listed by cohort and subject for the 
PKS. Concentration listings will include nominal PK sampling time, actual sampling times relative 
to dose administration, deviation from nominal time, and percent deviation from nominal time, and 
concentrations. Plasma concentrations below the lower limit of quantification (LLOQ) will be 
presented as below the lower limit of quantification (BLQ) in the listings. Missing PK samples will 
be reported as no sample (NS) and/or not reportable (NR) and considered to be excluded from PK 
analysis.  
In concentration listings, the individual concentrations will be reported to the same precision as the 
source data (for example, if the source data is presented to five significant digits in Bioanalytical 


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Lab deliverable, it will be programmed to same precision in SDTM and ADaM PK concentration 
datasets, and the individual values in the listings will be presented to five significant digits). 
Concentration Summary Tables: 
Tabular summaries for concentration-time data will report N (number of subjects who received 
treatment) and n (number of subjects with non-missing values). 
Concentration for mavacamten will be summarized by cohort, and nominal timepoint for the PKS. 
The following descriptive statistics will be presented for plasma concentrations obtained at each 
nominal time point: N, n, arithmetic mean, SD, coefficient of variation (CV%), geometric mean, 
geometric CV% (calculated as: gCV% =SQRT(es²-1)*100; where s is the SD of the log-transformed 
values), median, minimum, and maximum values. 
The rules followed for calculation and presentation of concentration data with regards to the number 
of decimal places/significant digits for the listings of subject level concentrations and summary 
tables of concentration are as follows:  
•
Source data will be used for calculation of concentration summary statistics.  
•
For presentation in concentration summary tables if less than 4 significant digits, all summary 
statistics will be tabulated to one more significant digit compared to the source data, otherwise 
up to a maximum of four significant digits, except that N and n will be presented as whole 
numbers.   
•
CV% and gCV% will be presented in one decimal place.  
Concentration Figures: 
To visualize subject-level concentrations and the comparison between each cohort, the descriptive 
PK graphs listed below will be generated.
•
Figure 1: Individual overlaid profiles for mavacamten (0-24h): Plasma Concentration Time 
Data – (Linear Scale and Semi-Logarithmic Scale) (PKS) 
•
Figure 2: Overlaid individual subject profiles for mavacamten: Plasma Concentration Time 
Data – (Linear Scale and Semi-Logarithmic Scale) (PKS)  
•
Figure 3: Mean (± SD) mavacamten overlaid profiles per cohort (0-24h): Plasma 
Concentration Time Data – (Linear Scale and Semi-Logarithmic Scale) (PKS) 
•
Figure 4: mavacamten Mean (± SD) overlaid profiles per cohort: Plasma Concentration Time 
Data – (Linear Scale and Semi-Logarithmic Scale) (PKS) 
Figures will be generated in color using unique line style and marker for each plot in the graph. For 
all PK concentration-time plots, linear scale will be used for x-axis (e.g., do not use an ordinal 
scale). 
4.8.2
Handling of Concentration Values Below the Limit of Quantification (BLQ) 
Derivation of plasma PK parameters 
•
BLQs at the beginning of a subject profile (i.e., before the first incidence of a measurable 
concentration) will be assigned to zero. 
•
BLQs at the end of a subject profile (i.e., after the last incidence of a measurable 
concentration) will be set to missing. 
•
Single BLQs which fall between two measurable concentrations will be set to missing. 


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•
Consecutive BLQs (2 or more) which fall between measurable concentrations will be set to 
missing. Measurable concentrations after consecutive BLQs will also be set to missing. 
Concentration Listings: 
All BLQ concentrations will be labeled as “BLQ” in the concentration data listings, and LLOQ 
value presented as a footnote. 
Concentration Figures: 
For arithmetic mean linear/linear graphs, all BLQ values will be substituted with zero for 
calculation of arithmetic mean and for log/linear graphs the log transformed arithmetic mean will be 
displayed (this should not include zero). 
For individual linear/linear and log/linear graphs all BLQ values will be substituted as follows: 
•
BLQs at the beginning of a subject profile (i.e., before the first incidence of a measurable 
concentration) will be assigned to zero (except for intravenous administration when these 
BLQs should not be displayed). When using log/linear scale, these timepoints will be 
considered missing. 
•
BLQs at the end of a subject profile (i.e., after the last incidence of a measurable 
concentration) will be set to missing. 
•
Single BLQs which fall between two measurable concentrations will be set to missing.  
•
Consecutive BLQs which fall between measurable concentrations will be set to missing. 
Measurable concentrations after consecutive BLQs will be set to missing. 
Concentration Tables: 
For summary tables, all BLQs will be considered zero, and number of BLQs and non-BLQs at each 
scheduled time point will be reported. Summary Statistics will not be calculated if non-BLQ 
concentrations at a scheduled time point is <3 and reported as NC. 
4.8.3
Pharmacokinetic Parameters 
Pharmacokinetic parameters will be calculated by non-compartmental analysis methods from the 
concentration-time data using Phoenix® WinNonlin® (Version 8.2) or higher following these 
guidelines: 
•
Actual time from dose will be used in the calculation of all derived pharmacokinetic 
parameters, except when parameters are calculated for safety/dose escalation meetings when 
nominal times may be used to calculate PK parameters.  
•
There will be no imputation of missing data.  
•
Any subjects with missing concentration data will be included in the PK analysis set provided 
that at least Cmax and AUC0-last can be reliably calculated. 
Pharmacokinetic parameters will be estimated according to the following guidelines: 
Table 4-1 Pharmacokinetic Parameter and Estimation 
Parameter 
Guideline for Derivation 
Cmax, tmax
Obtained directly from the observed concentration-time data 


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Parameter 
Guideline for Derivation 
AUC0-last
The AUC from zero time (pre-dose) to the time of last quantifiable concentration will be 
calculated by a combination of linear and logarithmic trapezoidal methods. Unless 
specifically requested and justified the linear up/log down trapezoidal method will be 
employed. 
The AUC0-last is the sum of areas up to the time of the last quantifiable sample: 
=
( )
AUC0-inf
The area from zero time extrapolated to infinite time will be calculated as follows:  
AUC0-inf = AUC0-t+
z
t
C
where Ct is the last observed quantifiable concentration. 
%AUCex
The percentage of AUC0-inf obtained by extrapolation will be calculated as follows:  
%
=
100
Unless otherwise determined by PK Scientist’s best knowledge and judgment, if the %AUCex
is greater than 30% the value,  %AUCex and all dependent parameters (ie, AUC0-inf, MRT, Vz 
and CL) will be flagged in listings and excluded from summary tables and statistical analysis 
of PK parameters, and if the %AUCex is greater than 20% but less than or equal to 30% the 
value, %AUCex and all dependent parameters (ie, AUC0-inf, MRT, Vz and CL) will be flagged 
in listings, but not excluded from summary tables and statistical analysis of PK parameters. 
The reason for exclusion will be footnoted in parameter listings.
t½ 
1. 
of concentration versus time data presented in a log-linear scale. 
2. 
Data are primarily monotonically decreasing in magnitude and are representative of 
the actual decline in the log concentration-time curve. 
3. 
Only those data points that are judged to describe the terminal log-linear decline will 
be used in the regression.  
4. 
A minimum number of three data points in the terminal phase will be used in 
max data point (Cmax should not 
be part of the regression slope). Unless otherwise determined by PK Scientist’s best 
knowledge and judgment, if the adjusted correlation coefficient (R2 adjusted) is <0.8, it will 
0-inf, CL, MRT, and Vz) will also be flagged and 
excluded from summary tables and statistical analysis. Any value of R2 between 0.8 and 0.9 
will be flagged but may be used at the PK Scientist’s best knowledge and judgement. The 
reason for exclusion will be footnoted in parameter listings.  
5. 
estimated t½ or otherwise flagged and used at the PK Scientist’s best knowledge and 
judgement. All derived parameters (i.e. t½, AUC0-inf, CL, MRT, and Vz) will also be 
flagged or excluded from statistical analysis of PK parameters accordingly. The reason for 
flagging and/or exclusion will be footnoted in parameter listings
6. 
The t½ will be calculated as follows:  
7. 
Data points may be dropped from the linear regression if the PK Scientist considers 
the reported values to be anomalous. Any data points so designated should remain in the 
listings with a footnote and be identified in the study report with a rationale for exclusion.
CL or CL/F 
Following IV administration, systemic clearance of parent drug will be calculated from:  
=
If desired, apparent clearance (CL/F) following extravascular (eg, oral) dosing 


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Parameter 
Guideline for Derivation 
may also be calculated.  In the case of steady state administration AUC
will be the 
denominator.
Vz or Vz/F 
Volume of distribution at terminal phase following either intravascular or extravascular 
dosing may be calculated from: 
=
=
(
/ )
Likewise, if derived for steady state 
administration AUC0- will be used.
DNCmax,DNAUC0-
last and 
DNAUC0-inf
DNCmax, DNAUC0-last and DNAUC0-inSf divided by dose 
PK Parameters Listings:  
For final analysis, Biostatistics group will be responsible for reporting individual PK parameters in 
the listing(s).  
Individual PK parameters will be presented to four significant digits, with the exception of tmax, 
which will be presented to two decimal places. Parameters derived directly from source data (e.g. 
Cmax,) shall be reported with the same precision as the source data (if this is not four significant 
digits).  
PK parameters will be listed by-subject for the PKS. PK parameters that will be excluded from 
summary tables and statistical analyses of PK parameters will be flagged and footnoted with the 
reason for exclusion.  
PK Parameter Summary Tables: 
Biostatistics group will use derived PK parameters source data without rounding for calculation of 
PK parameters summary statistics tables.  
PK parameters will be summarized by cohort for the PKS. 
Tabular summaries for PK parameters will report N (number of subjects who received treatment) 
and n (number of subjects with non-missing values). 
Descriptive statistics for calculated PK parameters will include N, n, arithmetic mean, SD, CV%, 
geometric mean, geometric CV%, median, minimum, and maximum values. For tmax, only n, 
median, minimum and maximum values will be presented. No descriptive statistics will be 
determined when fewer than three individual PK parameters are available. 
The rules followed for presentation of PK parameters data with regards to the number of decimal 
places/significant digits for the listings of subject level PK parameters and summary tables of PK 
parameters are as follows:  
•
all summary statistics will be tabulated to a maximum of 4 significant digits, with exception 
of tmax that is presented to 2 decimal places and N and n that will be presented as whole 
numbers.  Comparative estimates will be presented in 3 decimal places and confidence 
intervals in the form of percentages, CV%, and  %AUCex will be presented to two decimal 
places.  
PK Parameter Figures 


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To visualize the comparison between each cohort on PK parameter level, Box plots of dose-
normalized Cmax, AUC0-last and AUC0-inf and Dose-Normalized Box plots of Cmax (PKS), AUC0-last
and AUC0-inf will be generated according to CYP2C19 genotype (cohort):
•
Figure 4: Box plots of Cmax (PKS) 
•
Figure 5: Box plots of AUC0-last (PKS) 
•
Figure 6: Box plots of AUC0-inf (PKS) 
•
Figure 7: Dose-Normalized Box plots of Cmax (PKS) 
•
Figure 8: Dose-Normalized Box plots of AUC0-last (PKS) 
•
Figure 9: Dose-Normalized Box plots of AUC0-inf (PKS) 
4.8.4
Pharmacokinetic Analysis 
To examine the exposure to mavacamten for subjects with the UM/RM/NM vs IM vs PM genotype, 
analysis of variance (ANOVA) model will be constructed using log-transformed AUC(0–last), AUC(0–
inf) and Cmax. The dependent variable will be the ln-transformed primary PK parameters (AUC(0–last), 
AUC(0–inf) and Cmax) and the independent variables will include fixed effects for cohort and subject 
as a random effect. 
The reference group will be cohort 1 and test groups will be cohort 2 to cohort 4. Geometric least-
squares means for each cohort (cohort 1 and cohort2:UM/RM/NM, cohort 3:IM, cohort 4: PM), 
point estimates and associated 90% CIs for the ratios for each primary PK parameter will be 
produced in tabular format. Estimates of between -participant variability (%CVb) will also be 
provided.  
4.8.5
Population PK (PopPK) Analysis 
PopPK analysis will be conducted with the pooled data from the current study LB2001-101 and 
other mavacamten studies. Additional details on PopPK model development and analysis will be 
provided in a separate PopPK data analysis plan(DAP). 
4.9
Safety Evaluation 
All safety summaries and analyses will be based upon the SAS as defined in Section 4.4.1. 
4.9.1
Adverse Events 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
Version 23.1 or higher.
All AE summaries should provide the number and percentages of subjects reporting at least one AE 
and the total number of events reported. 
Summaries of AEs will include the following: 
•
Incidence of AEs - Overview (by cohort and overall) 
•
Incidence of drug taken period AEs(by cohort and overall, SOC, and PT) 
•
Incidence of drug taken period AEs by maximum relationship (by cohort and overall, SOC, 
and PT) 
•
Incidence of drug taken period AEs by maximum severity (mild/moderate/severe, by cohort 
and overall, SOC, and PT) 


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•
 Incidence of AESIs (by cohort and overall, SOC, and PT) 
Summary tables will contain counts of subjects, percentages of subjects in parentheses, and the 
number of events where applicable. A subject who has multiple events in the same SOC and PT will 
be counted only once in the subject counts, but all events will be included.
A by-subject listing of all adverse events (including non-treatment-emergent events) will be 
provided. This listing will be presented by cohort and will include: subject identifier, age, sex, race, 
adverse event (SOC, PT, and verbatim term), date of onset, date of resolution, duration, severity, 
seriousness, action taken, outcome and causality.  
All Adverse Events (AEs) 
All AEs will be listed including pre-treatment AEs, and pre-treatment SAE will be listed separately. 
Drug Taken Period Adverse Event 
Drug taken period AEs will be summarized by SOC and PT, including the number and percentage 
of subjects experiencing events, separately. 
Severity 
Drug taken period AEs will be summarized by SOC, PT, and severity, including the number and 
percentage of subjects experiencing events. If a subject reports the same drug taken period AE more 
than once within that SOC and PT, the drug taken period AE with the highest severity will be used 
in the corresponding severity summaries. 
In summaries including severity, the following intensity categories will be summarized: ‘Mild’, 
‘Moderate’, ‘Severe’. Subjects who experience the same event multiple times will be included in 
the most severe category. Events with missing intensity will be considered as ‘Severe’ events for 
summary purposes but recorded as missing in the listings. 
Relationship (Causality) 
Drug taken period AEs will be summarized by SOC, PT, and causality, including the number and 
percentage of subjects experiencing events. Relationship to study drug will be tabulated 
respectively. In summaries including severity, the following relationships will be summarized: 
‘unrelated’, ‘Related’.  If a subject reports the same drug taken period AE more than once within 
that SOC and PT, the drug taken period AE with the worst case relationship to study drug will be
used in the corresponding relationship summaries. Events with missing relationship will be 
considered as ‘Related’ to the last given study drug for summary purposes but recorded as missing 
in the listings. 
Adverse Events of Special Interests (AESIs) 
Adverse events of special interests (AESIs) will be summarized by SOC and PT, including the 
number and percentage of subjects experiencing events. Listing of AESI will be provided. 
4.9.2
Deaths, Serious Adverse Events, and Other Significant Adverse Events 
The following summaries will be provided by cohort and by MedDRA SOC and PT: 
•
SAEs 
•
Drug taken period SAEs 
•
Related SAEs to the study drug 
•
AEs leading to study discontinuation 


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•
AEs leading to death 
The following listings are to be provided: 
•
A by-subject listing of all deaths that occurred during the study 
•
A by-subject listing of all SAEs 
•
A by-subject listing of all AEs leading to discontinuation of study 
4.9.3
Clinical Laboratory Evaluation 
Descriptive statistics (for non-categorical data including hematology, coagulation function and 
blood chemistry) will be presented by cohort and time-point for both absolute values and changes 
from baseline.  
Frequency tabulations of qualitative clinical laboratory variables (urinalysis) will be presented by 
cohort and time-point. 
Shift tables will be presented for select laboratory parameters (Blood chemistry, coagulation 
function and hematology). 
Laboratory values (hematology, coagulation, biochemistry and urinalysis) will be listed by subject 
and study time point, including changes from baseline (with the exception of urinalysis).  
All values outside the clinical reference ranges will be flagged in the data listings. The abnormal 
values will be flagged with ‘L’ for values below the lower limit of the clinical reference range and 
‘H’ for values above the upper limit of the clinical reference range and included in the listings. The 
Investigator will assess whether the values outside the clinical reference range are clinically 
significant and these will be reported as abnormal not clinically significant (NCS) or abnormal 
clinically significant (CS). Clinically significant laboratory values will be recorded by the 
Investigator as AEs. 
4.9.4
Vital Signs, Physical Findings and Other Observations Related to Safety 
Vital Signs 
Descriptive statistics will be presented by cohort and time-point for absolute values and changes 
from baseline. 
A by-subject listing of all vital sign measurements and change from baseline will be presented by 
cohort and time point. 
ECG 
Descriptive statistics will be presented by cohort and time-point for absolute values and changes 
from baseline.  
A summary of the number and percentage of subjects with QTc exceeding some predefined upper 
limits (e.g. >450ms, >480ms, >500ms, >520ms, >550ms for measured values as well as. >30ms, 
>60ms for changes from baseline) of ECG parameters will be displayed in a frequency table. 
All ECG parameters will be listed by subject for each cohort and time point including changes from 
baseline.  
The listing of ECG abnormality will be presented separately. 
Physical Examination 


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The full physical examination includes an assessment of general appearance and a review of 
systems (general appearance, skin, head and neck, mouth, lymph nodes, thyroid, abdomen, and 
musculoskeletal, cardiovascular, neurological, and respiratory systems). 
The brief physical examination includes an assessment of the cardiovascular and respiratory 
examinations. 
Clinically significant physical exam findings will be listed. 
4.10 Handling of Dropouts or Missing Data 
No imputation of missing data will be performed except for partial dates imputation mention in 
Section 6.3. 
4.11 Planned Interim Analysis 
No interim analysis will be performed for this study. 
4.12 Determination of Sample Size 
No formal hypothesis testing will be conducted. The number of subjects in each cohort is expected 
to provide sufficient data to allow the assessment of the safety, tolerability and PK profile of 
mavacamten in Chinese subjects. Hence approximately 8-12 subjects will be enrolled in Phase I to 
obtain adequate PK and safety data based on China regulatory consideration. 
4.13 Explanation for Inconsistency with Planned Analysis 
In the study protocol, one of the laboratory biochemistry parameters collected is urea nitrogen, but 
since urea nitrogen is no longer applicable at the site, the item actually collected in the eCRF is urea. 
It is hereby stated that in this statistical analysis plan, urea nitrogen described in the protocol was 
changed to be urea, and indicators of urea actually collected were used for analysis. 
In the study protocol, the pharmacokinetic analysis set (PKS) was defined as: The pharmacokinetic 
(PK) analysis set consists of all subjects exposed to mavacamten with at least one plasma drug 
concentration result. 
In this analysis plan, the definition of pharmacokinetic analysis set (PKS) was additionally 
described. That subjects without serious protocol violations affecting PK parameter results were 
included in the analysis set was added to more accurately describe the PKS analysis set. The 
modified definition is as follows: The pharmacokinetic (PK) analysis set consists of all subjects 
exposed to mavacamten with at least one plasma drug concentration result and without serious 
protocol violations affecting PK parameter results. It is hereby stated. 
5
REFERENCES 
[1] SAS® Version 9.4 of the SAS System for Personal Computers. Copyright © 2002-2003. SAS 
Institute Inc. SAS and all other SAS Institute Inc. product or service names are registered 
trademarks or trademarks of SAS Institute Inc., Cary, NC, USA. 
[2] Phoenix®WinNonlin® Professional Software Version 8.2. https://www.certara.com 


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6
APPENDICES 
6.1
Schedule of Assessments 
Table 2 
Study Flow Chart
Weeks 
Pre-screening 
Screening 
Period 
In-house Period 
Outpatient Period 
End of 
study 
visit 
Days 
D-43 to D-15 
D-14 to 
D-2 
D-1 
D1
D2
D3
D7
D10
D14 
D21 D28
D35 
D45 
D60
D75 
Visit Window (day) 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
Signing 
the 
pre-screening 
ICF1
X 
Demographics2
X
CYP2C19 genotyping
X
Signing the main ICF
X
Inclusion/exclusion criteria
X
X
Assign subject number
X
X
X
Medical history
X
Vital signs3
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical examination4
X
X
X
X
Weight, height5
X
X
12-lead ECG6
X
X
X
X
X
X
X
Echocardiography
X
Hematology7
X
X
X
X
Blood chemistry8
X
X
X
X
X
Urinalysis9
X
X
X
X


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Weeks 
Pre-screening 
Screening 
Period 
In-house Period 
Outpatient Period 
End of 
study 
visit 
Days 
D-43 to D-15 
D-14 to 
D-2 
D-1 
D1
D2
D3
D7
D10
D14 
D21 D28
D35 
D45 
D60
D75 
Visit Window (day) 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
Coagulation10
X
X
X
X
X
FSH11
X
Serum pregnancy test12
X
X
Urine Pregnancy test12
X
X
X
Hepatitis B, C, and HIV 
virology
X 
Alcohol or drug abuse test13
X
X
Investigational drug14
X
PK blood sampling15
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X
X
X
X
X
X
X
X
AE16
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Abbreviations: AE = adverse event; ALP = alkaline phosphatase; ALT = alanine aminotransferase; APTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; BP = blood pressure; CK = creatine kinase; CYP = cytochrome P450; ECG = electrocardiogram; EOS = end of study; FIB = fibrinogen; FSH = follicle 
stimulating hormone; HIV = human immunodeficiency virus; HR = heart rate; ICF = informed consent form; INR = international normalized ratio; PK = pharmacokinetic; 
PT = prothrombin time; QD = once daily; RBC = red blood cell; SAE = serious AE; TT = thrombin time; WBC = white blood cell. 
Note: Safety laboratory assessments (Hematology, Biochemistry, Coagulation test, Urinalysis) has no need to be repeated on Day -1 if latest results are within 7 days.  
6.2
Schedule of PK Sampling 
3mL whole blood will be collected at each following time point for PK analysis. 


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Blood samples will be obtained to determine mavacamten concentrations at pre-dose and 10min, 20min, 30min, 45min, 1h, 1.5h, 2h, 3h, 4h, 8h, 12h, 
24h, and 48 hours after administration of mavacamten. Additional blood samples will be collected at Days 7, 10, 14, 21, 28, 35, 45, 60 and 75 (Table 
2). 
Table 2 
PK Sampling Schedule
In-house Period 
Outpatient Period 
End of 
study 
visit 
Days 
D 1 
D 2 
D 3 
D 7 
D 10 
D 14 
D 21 
D 28 
D 35 
D 45 
D 60 
D 75 
Visit 
Window 
(day) 
0 
0 
0 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
±1 
Collection 
time points 
Pre-dose (within 
60 min before 
dosing)
24 h ± 1 h 
post-dose 
48 h ± 1 h 
post-dose 
Outpatient 
visits: 
144 h ± 24 
h post-dose 
on Day 1 
Outpatient 
visits: 
216 h ± 24 
h post-dose 
on Day 1 
Outpatient 
visits: 
312 h ± 24 
h post-dose 
on Day 1 
Outpatient 
visits: 
480 h ± 24 
h post-dose 
on Day 1 
Outpatient 
visits: 
648 h ± 24 
h post-dose 
on Day 1 
Outpatient 
visits: 
816 h ± 24 
h post-dose 
on Day 1 
Outpatient 
visits: 
1056 h ± 24 
h post-dose 
on Day 1 
Outpatient 
visits: 
1416 h ± 
24 h post-
dose on 
Day 1 
EOS Visit: 
1776 h ± 24 h 
post-dose on 
Day 1 
10 min±2 min
20 min±2 min
30 min±2 min
45 min±2 min
1 h±2 min
1.5 h±3 min
2 h±3 min
3 h±3 min
4 h±3 min
8 h±5 min
12 h±5 min
6.3
Imputation Rules for Partial Dates 
Imputed dates will NOT be presented in the listings. In general, when calculating the relative study days, the imputation of the partial dates will be as 
follows: 
Incomplete Start Date 


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•
If only day is missing, date imputed will be 1st of the month. 
•
If both month and day are missing, January 1 will be imputed. 
Incomplete End Date 
•
If only day is missing, date imputed will be last day of the month. 
•
If both month and day are missing, December 31 will be imputed. 
Table  and Table 3 present algorithm for imputing partial dates for drug taken period AE and prior/concomitant medication respectively. 
Table 3 
Algorithm for Drug Taken Period Adverse Events: 
Start/Increase Severity Date 
Stop Date 
Action 
Known 
Known 
Considered as a drug taken period AE if start date on or after the date of 
the dose of investigational product (IP)  
Partial 
Considered as a drug taken period AE if start date on or after the date of 
the dose of IP. The last day of the month and the last month (i.e., 
December) will be used if the stop day/month is missing. 
Missing 
Considered as a drug taken period AE if start date on or after the date of 
the dose of IP 
Partial, but known components show that it cannot 
be on or after first IP taken date 
Known 
Not a drug taken period AE. The first day of the month and January will 
be used if the start day/month is missing. 


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Start/Increase Severity Date 
Stop Date 
Action 
Partial 
Not a drug taken period AE. The first day of the month and January will 
be used if the start day/month is missing. The last day of the month and 
the last month (ie, December) will be used if the stop day/month is 
missing. 
Missing 
Not a drug taken period AE. The first day of the month and January will 
be used if the start day/month is missing. 
Partial, could be on or after first IP taken date 
Known 
Considered as a drug taken period AE, if stop date is after first IP taken 
date. The first IP taken date will be used if start date is in the same 
month/year with first IP taken date, or the first day of the month and 
January will be used if the start day/month is after first IP taken date 
Considered as not  drug taken period AE, if stop date is prior to first IP 
taken date. The first day of the month and January will be used if the 
start day/month is missing. 
Partial 
Considered as a drug taken period AE. The first IP taken date will be 
used if start date is in the same month/year with first IP taken date, or the 
first day of the month and January will be used if the start day/month is 
after first IP taken date. The last day of the month and the last month (ie, 
December) will be used if the stop day/month is missing. 
Missing 
Considered as a drug taken period AE. The first IP taken date will be 
used if start date is in the same month/year with first IP taken date, or the 
first day of the month and January will be used if the start day/month is 
after first IP taken date. 


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Start/Increase Severity Date 
Stop Date 
Action 
Missing 
Known 
Considered as a drug taken period AE if stop date is on or after the date 
of the dose of IP. 
Partial 
The last day of the month and the last month (ie, December) will be used 
if the stop day/month is missing. If the imputed stop date is on or after 
the dose of IP considered as a drug taken period AE; if the year is 
missing, considered as a drug taken period AE. 
Missing 
Considered as a drug taken period AE 


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Table 3 
Algorithm for Prior/Concomitant Medications: 
Start Date 
Stop Date 
Action 
Known 
Known 
If stop date is prior to the date for the dose of IP, considered as prior; if stop date are on or after the 
date for the dose of IP, considered as concomitant. 
Partial 
The last day of the month and the last month (ie, December) will be used if the day/month of stop date 
is missing.  
If the impuated stop date is prior to the date for the dose of IP, considered as prior; if the imputed stop 
date are on or after the date for the dose of IP, considered as concomitant. 
Missing 
Considered as concomitant. 
Partial 
Known 
The first day of the month and January will be used if the start day/month is missing.  
If stop date is prior to the date for the dose of IP, considered as prior; If stop date are on or after the 
date for the dose of IP, considered as concomitant. 
Partial 
The first day of the month and January will be used if the start day/month is missing.The last day of 
the month and the last month (ie, December) will be used if the day/month of stop date is missing.  
If the imputed stop date is prior to the date for the dose of IP, considered as prior; If imputed stop date 
are on or after the date for the dose of IP, considered as concomitant. 
Missing 
Considered as concomitant.  
Missing 
Known 
If stop date is prior to the date for the dose of IP, considered as prior; if stop date is on or after the date 
for the dose of IP, considered as concomitant. 


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Start Date 
Stop Date 
Action 
Partial 
The last day of the month and the last month (ie, December) will be used if the day/month of stop date 
is missing. If the imputed stop date is prior to the date for the dose of IP, considered as prior; if he 
imputed stop date is on or after the date for the dose of IP, considered as concomitant. 
Missing 
Considered as concomitant.