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

Phase 2TerminatedNCT02862600

Heart Metabolics Limited35 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Cardiomyopathy, Hypertrophic Cardiomyopathy, Hypertrophic, Familial

Interventions

PerhexilineDRUG

Period 1 (Weeks 1-8) and Period 2 (Weeks 9-16): dose titrated to two different plasma levels of perhexiline

Use of bioanalytical assay to monitor plasma levels of perhexilineDEVICE

The bioanalytical assay is the device under investigation. It will be used to monitor plasma levels of perhexiline. The data obtained from this analysis will be used to guide dose adjustments of perhexiline.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (11)

Unnamed facility

Stanford, California, United States

Unnamed facility

Indianapolis, Indiana, United States

Johns Hopkins

Baltimore, Maryland, United States

University of Maryland

Baltimore, Maryland, United States

Outcomes

Primary Outcomes

Change From Baseline of VO2MAX at 16 Weeks

At the conclusion of 16 weeks of perhexiline treatment, MVO2 was measured using CPEX and compared to MVO2 measured at baseline.

Time frame: end of Period 2 (Week 16)

Secondary Outcomes

Change From Baseline of VO2MAX at End of Period 1

At the conclusion of 8 weeks of perhexiline treatment, MVO2 was measured using CPEX and compared to MVO2 measured at baseline.

Time frame: end of Period 1 (Week 8)

Change From Baseline in the Six-minute Walk Test at the End of Period 2

At the conclusion of 16 weeks of perhexiline treatment, 6MWD was measured and compared to 6MWD measured at baseline.

Time frame: end of Period 2 (Week 16)

Change From Baseline in the Six-minute Walk Test at the End of Period 1

At the conclusion of 8 weeks of perhexiline treatment, 6MWD was measured and compared to 6MWD measured at baseline.

Time frame: end of Period 1 (Week 8)

Data from ClinicalTrials.gov

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