Open-Label Study of Perhexiline in Patients With Hypertrophic Cardiomyopathy and Moderate to Severe Heart Failure

Phase 2

Terminated

Conditions: Cardiomyopathy, Hypertrophic
Cardiomyopathy, Hypertrophic, Familial

Interventions: Drug: Perhexiline
Device: Use of bioanalytical assay to monitor plasma levels of perhexiline

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Perhexiline	Use of bioanalytical assay to monitor plasma levels of perhexiline	Perhexiline will be administered orally. Dosing will be determined based on plasma level monitoring. For the first 8 week period, the target range will be 100-300 ng/mL, for the second 8 week period, the target range will be 300-500 ng/mL.
Perhexiline	Perhexiline	Perhexiline will be administered orally. Dosing will be determined based on plasma level monitoring. For the first 8 week period, the target range will be 100-300 ng/mL, for the second 8 week period, the target range will be 300-500 ng/mL.

Primary Outcome Measures

Name	Time	Method
Change From Baseline of VO2MAX at 16 Weeks	end of Period 2 (Week 16)	At the conclusion of 16 weeks of perhexiline treatment, MVO2 was measured using CPEX and compared to MVO2 measured at baseline.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline of VO2MAX at End of Period 1	end of Period 1 (Week 8)	At the conclusion of 8 weeks of perhexiline treatment, MVO2 was measured using CPEX and compared to MVO2 measured at baseline.
Change From Baseline in the Six-minute Walk Test at the End of Period 2	end of Period 2 (Week 16)	At the conclusion of 16 weeks of perhexiline treatment, 6MWD was measured and compared to 6MWD measured at baseline.
Change From Baseline in the Six-minute Walk Test at the End of Period 1	end of Period 1 (Week 8)	At the conclusion of 8 weeks of perhexiline treatment, 6MWD was measured and compared to 6MWD measured at baseline.