Open-Label Study of Perhexiline in Patients With Hypertrophic Cardiomyopathy and Moderate to Severe Heart Failure
Open-Label Study of Perhexiline in Patients With Hypertrophic Cardiomyopathy and Moderate to Severe Heart Failure
The purpose of this study is to evaluate the effect of perhexiline on exercise performance
 (efficacy) and safety in patients with hypertrophic cardiomyopathy and moderate-to-severe
 heart failure following dosing for 16 weeks.
Patients with hypertrophic cardiomyopathy and symptoms without severe outflow obstruction
 will be eligible to participate. Enrollment will be limited to subjects who are unable to
 attain 75% of their maximum predicted MVO2 at cardiopulmonary exercise testing. Subjects with
 genetic evidence of CYP2D6 poor metabolizer status will be excluded.

 Subjects will undergo functional testing at baseline with CPEX testing and 6 minute walk
 distance testing. They will begin perhexiline orally, and the dose will be adjusted according
 to plasma level testing. For the first 8 week period, the target therapeutic range will be
 100-300 ng/mL, and for the second 8 week period, the range will be 300-500 ng/mL. Functional
 testing will be repeated at the end of both periods.
Key Inclusion Criteria:

 -  Hypertrophic cardiomyopathy with symptoms of moderate-to-severe heart failure

 -  Left ventricular hypertrophy with maximum LV wall thickness ≥ 15 mm

 -  Left ventricular ejection fraction ≥ 50%

 -  Able to perform exercise testing but unable to exceed 75% of the predicted
 age-adjusted maximum level

 Key Exclusion Criteria:

 -  CYP2D6 Poor Metabolizer (PM) status

 -  History of a known chronic liver disease

 -  ALT, AST, alkaline phosphatase, or LDH > 1.5 x upper limit of normal

 -  Total Bilirubin > 2.0 x upper limit of normal

 -  Severe LV outflow obstruction

 -  Asymptomatic patients or cardiomyopathy-related criteria as per protocol

 -  QT interval related criteria as per protocol