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

Heart Metabolics

Status and phase: Terminated; Phase 2

Conditions: Cardiomyopathy, Hypertrophic, Familial; Cardiomyopathy, Hypertrophic

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02862600

HML-PHX-005

Details and patient eligibility

About

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.

Full 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.

Enrollment: 35 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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35 participants in 1 patient group

Perhexiline

Experimental group

Description:

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.

Treatment:

Drug: Perhexiline

Device: Use of bioanalytical assay to monitor plasma levels of perhexiline