Efficacy, Safety, and Tolerability of Perhexiline in Subjects With Hypertrophic Cardiomyopathy and Heart Failure

Inclusion Criteria: General Criteria 1. Adult, at least 18 years of age 2. Able and willing to give written informed consent Cardiomyopathy-related Criteria 3. Hypertrophic cardiomyopathy (HCM) with moderate-to-severe heart failure as defined as meeting all of the following criteria: 1. HCM meeting the 2011 ACCF/AHA Criteria for the Diagnosis of Hypertrophic Cardiomyopathy (Gersh et al. 2011) 2. Left ventricular hypertrophy (LVH) with maximum LV wall thickness \> 15 mm by echocardiography or cardiac magnetic resonance imaging without an alternative explanation 3. Left ventricular ejection fraction (LVEF) \> 40% 4. Able to perform exercise testing but unable to exceed 75% of the predicted age-adjusted maximum level(as determined by METs achieved during exercise testing-eligibility is not based on VO2max) 4. Normal sinus rhythm at Screening and Baseline (atrial fibrillation pattern acceptable for subjects with known chronic atrial fibrillation) 5. If taking any medications for the treatment of HCM (including beta-blockers, calcium channel blockers, disopyramide, diuretics), the medication has been taken a stable dose for at least 60 days prior to enrollment and will be continued at the same dose throughout the study Exclusion Criteria: General Criteria 1. Pregnant women, women who intend to become pregnant, or woman who are not practicing contraception, either pharmacologically or with a barrier method 2. Lactating women 3. CYP2D6 Poor Metabolizer (PM) status, based on genotype known prior to Screening, or as predicted by genotype assessed at Screening CYP2D6 Poor Metabolizer (PM) status is defined as having no functional CYP2D6 alleles by genotyping (exclusively having allele combinations of \*3, \*4, \*5, \*6, \*7, \*8, \*12, \*14). 4. Any subject who regularly takes a medication known to be a strong inhibitor of CYP2D6 (bupropion, fluoxetine, paroxetine, quinidine, or ritonavir) 5. Any concomitant disease, condition, or treatment that could interfere with the conduct of the study, or that would, in the opinion of the investigator or sponsor, pose an unacceptable risk to subjects and/or interfere with the interpretation of study data, including but not limited to: 1. History of a known toxic or inflammatory peripheral neuropathy, such as mononeuritis multiplex, acute or chronic inflammatory demyelinating polyneuropathy (AIDP or CIDP), axonal sensorimotor neuropathies, drug-related neuropathy or neuritis, or diabetic neuropathy (history of a compression neuropathy, such as carpal tunnel syndrome, is acceptable) 2. Poorly controlled diabetes mellitus (e.g., HbA1c \> 8.5%) 3. Clinically severe chronic obstructive pulmonary disease (i.e. COPD requiring home oxygen or history of IV or oral steroid use) 4. History of a known chronic liver disease including cirrhosis of any cause, or chronic hepatitis B or hepatitis C 5. History of porphyria 6. History of recurrent hypoglycemia 7. Active infection requiring antibiotics 8. Life expectancy of less than 2 years 9. Evidence of an active or suspected cancer or a history of malignancy, except for skin squamous cell or basal cell carcinomas that did not require systemic therapy and are considered to be cured 10. History of substance abuse, including alcohol or illicit drugs within the past 12 months 11. Abnormal safety studies of clinical significance at Screening such as: i. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, or lactate dehydrogenase \> 1.5X upper limit of normal (ULN) ii. Glucose \< 70 mg/dL iii. Prolonged QTc (\>450 msec) l. Known hypersensitivity to perhexiline maleate 6. Unable or unwilling to comply with the protocol 7. Enrolled in another therapeutic trial for hypertrophic cardiomyopathy Cardiomyopathy-related Exclusion Criteria 8. Asymptomatic subjects or subjects whose symptoms are controlled with medications 9. Resting LVOT gradient \> 50 mmHg or known exercise-induced LVOT gradient \> 80 mmHg 10. Absence of an implanted, operational ICD if there is a history of frequent non-sustained ventricular tachycardia, or a first degree relative having had sudden cardiac death or ICD implant 11. Known coronary artery disease (\> 50% arterial luminal narrowing of a major epicardial vessel) 12. History of cardiac transplantation 13. Cardiac surgery or septal reduction surgery planned or having occurred within past 6 months 14. HCM believed to be caused by infiltrative disorders, glycogen storage disorders, and hypertensive heart disease (including genotypic or phenotypic evidence of Fabry's Disease)