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

Primary Purpose

Cardiomyopathy, Hypertrophic, Cardiomyopathy, Hypertrophic, Familial

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Perhexiline
Use of bioanalytical assay to monitor plasma levels of perhexiline
Sponsored by
Heart Metabolics Limited
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cardiomyopathy, Hypertrophic focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Johns Hopkins
  • University of Maryland

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Perhexiline

Arm 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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
August 8, 2016
Last Updated
August 2, 2017
Sponsor
Heart Metabolics Limited
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1. Study Identification

Unique Protocol Identification Number
NCT02862600
Brief Title
Open-Label Study of Perhexiline in Patients With Hypertrophic Cardiomyopathy and Moderate to Severe Heart Failure
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Terminated
Why Stopped
Lack of Efficacy
Study Start Date
August 1, 2016 (Actual)
Primary Completion Date
April 28, 2017 (Actual)
Study Completion Date
May 22, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Heart Metabolics Limited

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Open-label, 2 period, dose escalation study of perhexiline in symptomatic patients with hypertrophic cardiomyopathy
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Perhexiline
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Perhexiline
Intervention Description
Period 1 (Weeks 1-8) and Period 2 (Weeks 9-16): dose titrated to two different plasma levels of perhexiline
Intervention Type
Device
Intervention Name(s)
Use of bioanalytical assay to monitor plasma levels of perhexiline
Intervention Description
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 Measure Information:
Title
Change From Baseline of VO2MAX at 16 Weeks
Description
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 Outcome Measure Information:
Title
Change From Baseline of VO2MAX at End of Period 1
Description
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)
Title
Change From Baseline in the Six-minute Walk Test at the End of Period 2
Description
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)
Title
Change From Baseline in the Six-minute Walk Test at the End of Period 1
Description
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Midei, MD
Organizational Affiliation
Heart Metabolics
Official's Role
Study Chair
Facility Information:
City
Stanford
State/Province
California
Country
United States
City
Indianapolis
State/Province
Indiana
Country
United States
Facility Name
Johns Hopkins
City
Baltimore
State/Province
Maryland
Country
United States
Facility Name
University of Maryland
City
Baltimore
State/Province
Maryland
Country
United States
City
Detroit
State/Province
Michigan
Country
United States
City
Columbus
State/Province
Ohio
Country
United States
City
Portland
State/Province
Oregon
Country
United States
City
Hershey
State/Province
Pennsylvania
Country
United States
City
Germantown
State/Province
Tennessee
Country
United States
City
Salt Lake City
State/Province
Utah
Country
United States
City
Madison
State/Province
Wisconsin
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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