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

NCT02862600 | Terminated Phase 2 Results FDA Drug FDA Device

• 1 other identifier: HML-PHX-005
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 11

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.

Conditions

Cardiomyopathy, Hypertrophic; Cardiomyopathy, Hypertrophic, Familial

Keywords

hypertrophic cardiomyopathy; heart failure; cardiopulmonary exercise testing; 6 minute walk test; perhexiline; carnitine palmitoyltransferase; mixed ion channel effects; late sodium current inhibitor; calcium channel inhibition

Outcome Measures

Primary Outcomes (1)

• 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.

  end of Period 2 (Week 16)

Secondary Outcomes (3)

• Change From Baseline of VO2MAX at End of Period 1

  end of Period 1 (Week 8)

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

  end of Period 2 (Week 16)

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

  end of Period 1 (Week 8)

Study Arms (1)

Perhexiline

EXPERIMENTAL

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.

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

Interventions

Perhexiline DRUG

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

Perhexiline

Use of bioanalytical assay to monitor plasma levels of perhexiline DEVICE

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.

Perhexiline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Heart Metabolics Limited: lead

Study Sites (11)

Unknown Facility

Stanford, California, United States

Location

Unknown Facility

Indianapolis, Indiana, United States

Location

Johns Hopkins

Baltimore, Maryland, United States

Location

University of Maryland

Baltimore, Maryland, United States

Location

Unknown Facility

Detroit, Michigan, United States

Location

Unknown Facility

Columbus, Ohio, United States

Location

Unknown Facility

Portland, Oregon, United States

Location

Unknown Facility

Hershey, Pennsylvania, United States

Location

Unknown Facility

Germantown, Tennessee, United States

Location

Unknown Facility

Salt Lake City, Utah, United States

Location

Unknown Facility

Madison, Wisconsin, United States

Location

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic; Cardiomyopathy, Hypertrophic, Familial; Heart Failure

Interventions

Perhexiline

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Early termination due to lack of efficacy in the first 15 subjects completing the study. Any conclusions regarding safety or efficacy a challenging in light of the small numbers of subjects studied.

Results Point of Contact

• Title: Mark G. Midei, MD, Executive Director and Head of Cardiology
• Organization: Heart Metabolics, Ltd.

markgmidei@gmail.com

4103715357

Study Officials

• Mark Midei, MD

  Heart Metabolics

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, 2 period, dose escalation study of perhexiline in symptomatic patients with hypertrophic cardiomyopathy

Study Record Dates

• First Submitted: August 8, 2016
• First Posted: August 11, 2016
• Study Start: August 1, 2016
• Primary Completion: April 28, 2017
• Study Completion: May 22, 2017
• Last Updated: August 31, 2017
• Results First Posted: August 31, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)