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

• ClinicalTrials.gov Identifier: NCT02862600
• Recruitment Status: Terminated
• First Posted: August 11, 2016
• Results First Posted: August 31, 2017
• Last Update Posted: August 31, 2017
• Sponsor: Heart Metabolics Limited
• Information provided by (Responsible Party): Heart Metabolics Limited

Tracking Information

• First Submitted Date: August 8, 2016
• First Posted Date: August 11, 2016
• Results First Submitted Date: June 25, 2017
• Results First Posted Date: August 31, 2017
• Last Update Posted Date: August 31, 2017
• Actual Study Start Date: August 1, 2016
• Actual Primary Completion Date: April 28, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 2, 2017)

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.

• Original Primary Outcome Measures (submitted: August 8, 2016): Change from baseline of VO2MAX [ Time Frame: end of Period 2 (Week 16) ]

Current Secondary Outcome Measures (submitted: August 2, 2017)

• 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.
• 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.
• 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.

Original Secondary Outcome Measures (submitted: August 8, 2016)

• Change from baseline of VO2MAX [ Time Frame: end of Period 1 (Week 8) ]
• Change from baseline of VO2MAX [ Time Frame: end of Period 1 (Week 8) compared to end of Period 2 (Week 16) ]
• Change from baseline in the six-minute walk test [ Time Frame: end of Period 1 (Week 8) ]
• Change from baseline in the six-minute walk test [ Time Frame: end of Period 2 (Week 16) ]
• Change from baseline in the six-minute walk test [ Time Frame: end of Period 1 (Week 8) compared to end of Period 2 (Week 16) ]
• Safety measures to include assessments of adverse events, vital signs, ECGs, and laboratory assay results [ Time Frame: during Period 1 (Weeks 1-8) compared to during Period 2 (Weeks 9-16) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

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

Condition

• Cardiomyopathy, Hypertrophic
• Cardiomyopathy, Hypertrophic, Familial

Intervention

• 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.

Study Arms

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.

Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: August 2, 2017): 35
• Original Estimated Enrollment (submitted: August 8, 2016): 33
• Actual Study Completion Date: May 22, 2017
• Actual Primary Completion Date: April 28, 2017 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02862600
• Other Study ID Numbers: HML-PHX-005
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Heart Metabolics Limited
• Original Responsible Party: Same as current
• Current Study Sponsor: Heart Metabolics Limited
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Mark Midei, MD; Heart Metabolics

• PRS Account: Heart Metabolics Limited
• Verification Date: August 2017