Inclusion Criteria:

• Able to understand and comply with the study procedures, understand the risks involved in the study, and provide written informed consent according to federal, local, and institutional guidelines before the first study-specific procedure.
• Is at least 18 years old at Screening.
• Body weight is greater than 45 kg at Screening.
• Has adequate acoustic windows to enable accurate TTEs (refer to Echocardiography Site Instruction Manual).
• Diagnosed with oHCM consistent with current AACF/AMA and ESC guidelines; i.e., satisfy both criteria below (criteria to be documented by the echocardiography core laboratory):
  • Has unexplained LV hypertrophy with nondilated ventricular chambers in the absence of other cardiac (eg, hypertension, aortic stenosis) or systemic disease and with maximal LV wall thickness ≥15 mm (or ≥13 mm with positive family history of HCM) as determined by core laboratory interpretation;
  • Has LVOT peak gradient ≥50 mmHg during Screening as assessed by echocardiography at rest, after Valsalva maneuver, or post-exercise (confirmed by echocardiography core laboratory interpretation).
• Has documented LVEF ≥55% by echocardiography core laboratory read of Screening TTE at rest.
• Has LVOT gradient with Valsalva maneuver at Screening TTE of ≥30 mmHg, determined by echocardiography core laboratory.
• Has NYHA Functional Class II or III symptoms at Screening.
• Has documented oxygen saturation at rest ≥90% at Screening.
• Is able to perform an upright CPET and has a respiratory exchange ratio (RER) ≥1.0 at Screening per central reading; if the RER is between 0.91 and 1.0, the participant may be enrolled only if it is determined by the central CPET laboratory that peak exercise has been achieved in the subject (the only permitted reasons for subpeak performance are [1] a decrease in systolic blood pressure (SBP) or [2] severe angina as described in the CPET Laboratory Manual).
• Female participants must not be pregnant or lactating and, if sexually active, must use one of the following highly effective birth control methods from the Screening visit through 3 months after the last dose of investigational medicinal product (IMP).
  • combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation or progestogen-only hormonal contraception associated with inhibition of ovulation by oral, implantable, or injectable route of administration;
  • intrauterine device (IUD);
  • intrauterine hormone-releasing system (IUS);
  • bilateral tubal occlusion;
  • Female is surgically sterile for 6 months or postmenopausal for 1 year. Permanent sterilization includes hysterectomy, bilateral oophorectomy, bilateral salpingectomy, and/or documented bilateral tubal occlusion 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 follicle stimulating hormone levels (FSH) are in the postmenopausal range.
• Male partners must also use a contraceptive (e.g., barrier, condom or vasectomy).

Exclusion Criteria:

• Previously participated in a clinical study with mavacamten.
• Hypersensitivity to any of the components of the mavacamten formulation.
• Participated in a clinical trial in which the participant received any investigational drug (or is currently using an investigational device) within 30 days prior to Screening, or at least 5 times the respective elimination half-life (whichever is longer)
• Known infiltrative or storage disorder causing cardiac hypertrophy that mimics oHCM, such as Fabry disease, amyloidosis, or Noonan syndrome with LV hypertrophy.
• Has any medical condition that precludes upright exercise stress testing.
• Has a history of syncope within 6 months prior to screening or history of sustained ventricular tachyarrhythmia with exercise within 6 months prior to Screening.
• Has a history of resuscitated sudden cardiac arrest (at any time) or known history of appropriate ICD discharge/shock for life-threatening ventricular arrhythmia within 6 months prior to Screening (Note: history of anti-tachycardia pacing (ATP) within 6 months or ever is allowed).
• Has paroxysmal, intermittent atrial fibrillation with atrial fibrillation present per the investigator’s evaluation of the participant’s ECG at the time of Screening.
• Has persistent or permanent atrial fibrillation not on anticoagulation for at least 4 weeks prior to Screening and/or not adequately rate controlled within 6 months of Screening.
  • Note – patients with persistent or permanent atrial fibrillation who are anticoagulated and adequately rate-controlled are allowed.
• Current treatment (within 14 days prior to Screening) or planned treatment during the study with disopyramide or ranolazine .
• Current treatment (within 14 days prior to Screening) or planned treatment during the study with a combination of β-blockers and verapamil or a combination of β-blockers and diltiazem.
• For individuals on β-blockers, verapamil, or diltiazem, any dose adjustment of that medication <14 days prior to Screening or an anticipated change in treatment regimen using these medications during the study.
• Has been successfully treated with invasive septal reduction (surgical myectomy or percutaneous ASA) within 6 months prior to Screening or plans to have either of these treatments during the study (note: individuals with myectomy or percutaneous ASA performed >6 months prior to Screening may be enrolled if study eligibility criteria for LVOT gradient criteria are met).
• ICD placement or pulse generator change within 2 months prior to Screening or planned new ICD placement during the study (pulse generator changes, if needed during the study, are allowed).
• Has QT interval with Fridericia correction (QTcF) >500 ms at Screening or any other ECG abnormality considered by the investigator to pose a risk to participant safety (eg, second-degree atrioventricular block type II).
• Has documented obstructive coronary artery disease (>70% stenosis in one or more epicardial coronary arteries) or history of myocardial infarction.
• Has known moderate or severe (as per investigator’s judgment) aortic valve stenosis at Screening.
• Has any acute or serious comorbid condition (eg, major infection or hematologic, renal, metabolic, gastrointestinal, or endocrine dysfunction) that, in the judgment of the investigator, could lead to premature termination of study participation or interfere with the measurement or interpretation of the efficacy and safety assessments in the study.
• Has pulmonary disease that limits exercise capacity or systemic arterial oxygen saturation.
• History of malignant disease within 10 years of Screening:
  • Participants who have been successfully treated for nonmetastatic cutaneous squamous cell or basal cell carcinoma or have been adequately treated for cervical carcinoma in situ or breast ductal carcinoma in situ (DCIS) can be included in the study;
  • Participants with other malignancies who are cancer-free for more than 10 years before Screening can be included in the study.
• Has safety laboratory parameters (chemistry, hematology, coagulation, and urinalysis) outside normal limits (according to the central laboratory reference range) at Screening as assessed by the central laboratory; however, a participant with safety laboratory parameters outside normal limits may be included if he or she meets all of the following criteria:
  • The safety laboratory parameter outside normal limits is considered by the investigator to be clinically not significant;
  • If there is an alanine aminotransferase or aspartate aminotransferase result, the value must be <3 × the upper limit of the laboratory reference range;
  • The body size–adjusted estimated glomerular filtration rate is ≥0 mL/min/1.73 m2.
• Has a positive serologic test at Screening for infection with human immunodeficiency virus, hepatitis C virus, or hepatitis B virus.
• Has a history or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator, would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion
• Is currently taking, or has taken within 14 days prior to Screening, a prohibited medication, such as a cytochrome P450 (CYP) 2C19 inhibitor (e.g., omeprazole or esomeprazole), a strong CYP 3A4 inhibitor, or St. John’s Wort. Alternatives, such as pantoprazole, are allowed and may be discussed with the medical monitor.
• Prior treatment with cardiotoxic agents such as doxorubicin or similar.
• Unable to comply with the study requirements, including the number of required visits to the clinical site.
• Is a first degree relative of personnel directly affiliated with the study at the clinical study site, any study vendor, or the study Sponsor.