Clinical trial NCT02862600: 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
Overall status: TERMINATED
Phase: PHASE2
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
Lead sponsor: Heart Metabolics Limited
Sponsor class: INDUSTRY
First posted: 2016-08-11
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, 2 period, dose escalation study of perhexiline in symptomatic patients with hypertrophic cardiomyopathy
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change From Baseline of VO2MAX at 16 Weeks
timeFrame: end of Period 2 (Week 16)
Secondary outcomes:
measure: Change From Baseline of VO2MAX at End of Period 1
timeFrame: end of Period 1 (Week 8)
measure: Change From Baseline in the Six-minute Walk Test at the End of Period 2
timeFrame: end of Period 2 (Week 16)
measure: Change From Baseline in the Six-minute Walk Test at the End of Period 1
timeFrame: end of Period 1 (Week 8)
Other outcomes:
Locations:
city: Stanford
country: United States
state: California
city: Indianapolis
country: United States
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins
state: Maryland
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Detroit
country: United States
state: Michigan
city: Columbus
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Hershey
country: United States
state: Pennsylvania
city: Germantown
country: United States
state: Tennessee
city: Salt Lake City
country: United States
state: Utah
city: Madison
country: United States
state: Wisconsin
Study officials:
affiliation: Heart Metabolics
name: Mark Midei, MD
role: STUDY_CHAIR
References: