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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02862600
Recruitment Status : Terminated (Lack of Efficacy)
First Posted : August 11, 2016
Results First Posted : August 31, 2017
Last Update Posted : August 31, 2017
Sponsor:
Information provided by (Responsible Party):
Heart Metabolics Limited

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.

Condition or disease Intervention/treatment Phase
Cardiomyopathy, Hypertrophic Cardiomyopathy, Hypertrophic, Familial Drug: Perhexiline Device: Use of bioanalytical assay to monitor plasma levels of perhexiline Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Open-label, 2 period, dose escalation study of perhexiline in symptomatic patients with hypertrophic cardiomyopathy
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Multi-Center, Open-Label, Ascending Dose Study on the Efficacy, Safety and Tolerability of Perhexiline in Patients With Hypertrophic Cardiomyopathy and Moderate to Severe Heart Failure With Preserved Left Ventricular Function
Actual Study Start Date : August 1, 2016
Actual Primary Completion Date : April 28, 2017
Actual Study Completion Date : May 22, 2017


Arm Intervention/treatment
Experimental: 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.
Drug: Perhexiline
Period 1 (Weeks 1-8) and Period 2 (Weeks 9-16): dose titrated to two different plasma levels of perhexiline

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




Primary Outcome Measures :
  1. Change From Baseline of VO2MAX at 16 Weeks [ Time Frame: 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 :
  1. Change From Baseline of VO2MAX at End of Period 1 [ Time Frame: 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.

  2. Change From Baseline in the Six-minute Walk Test at the End of Period 2 [ Time Frame: 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.

  3. Change From Baseline in the Six-minute Walk Test at the End of Period 1 [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02862600


Locations
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United States, California
Stanford, California, United States
United States, Indiana
Indianapolis, Indiana, United States
United States, Maryland
Johns Hopkins
Baltimore, Maryland, United States
University of Maryland
Baltimore, Maryland, United States
United States, Michigan
Detroit, Michigan, United States
United States, Ohio
Columbus, Ohio, United States
United States, Oregon
Portland, Oregon, United States
United States, Pennsylvania
Hershey, Pennsylvania, United States
United States, Tennessee
Germantown, Tennessee, United States
United States, Utah
Salt Lake City, Utah, United States
United States, Wisconsin
Madison, Wisconsin, United States
Sponsors and Collaborators
Heart Metabolics Limited
Investigators
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Study Chair: Mark Midei, MD Heart Metabolics
  Study Documents (Full-Text)

Documents provided by Heart Metabolics Limited:
Study Protocol  [PDF] December 2, 2016
Statistical Analysis Plan  [PDF] June 1, 2017
Informed Consent Form  [PDF] July 13, 2016

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Responsible Party: Heart Metabolics Limited
ClinicalTrials.gov Identifier: NCT02862600    
Other Study ID Numbers: HML-PHX-005
First Posted: August 11, 2016    Key Record Dates
Results First Posted: August 31, 2017
Last Update Posted: August 31, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Keywords provided by Heart Metabolics Limited:
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
Additional relevant MeSH terms:
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Heart Failure
Cardiomyopathies
Cardiomyopathy, Hypertrophic
Cardiomyopathy, Hypertrophic, Familial
Hypertrophy
Heart Diseases
Cardiovascular Diseases
Pathological Conditions, Anatomical
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Heart Valve Diseases
Genetic Diseases, Inborn
Perhexiline
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Vasodilator Agents