Efficacy, Safety, and Tolerability of Perhexiline in Subjects With Hypertrophic Cardiomyopathy and Heart Failure

NCT02431221 | Withdrawn Phase 3 DMC

• 1 other identifier: HM-PHX-003
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

A Study on the Efficacy, Safety, and Tolerability of Perhexiline maleate in Subjects with Hypertrophic Cardiomyopathy and Moderate-To-Severe Heart Failure

Conditions

Hypertrophic Cardiomyopathy

Keywords

perhexiline; HCM; Hypertrophic Cardiomyopathy; CPEX

Outcome Measures

Primary Outcomes (1)

• Subject Outcome Variable

  The subject Outcome variable is a rank-ordered, hierarchical classification of outcome variables followed by a rank ordering of change from baseline in Maximum oxygen consumption

  6 months after randomization

Secondary Outcomes (3)

• Functional Assessment During Randomized Withdrawal Phase

  6 months after initiation of open label period, and 3 months after randomized withdrawal period initiated

• Functional Assessment During Randomized Phase

  6 months after Randomization

• Functional Assessment During Randomized Withdrawal Phase

  6 months after initiation of open label period, and 3 months after randomized withdrawal period initiated

Study Arms (2)

Intervention

EXPERIMENTAL

Perhexiline maleate will be supplied in 100 mg and 25 mg tablets. It will be initially administered at a dose of 200 mg once a day in tablet form for at least six months. After initiation of dosing, perhexiline dosing will be determined using plasma level guided dose adjustment. Dosing decisions will be made by an unblinded dose control center.

Drug: Perhexiline

Placebo

PLACEBO COMPARATOR

Placebo will be administered once a day in tablet form for at least six months. Tablets will be identical in size and shape to perhexiline tablets. Adjustments in placebo dosing will be made by an unblinded dose control center to mimic decisions made for subjects in the experimental arm.

Drug: Placebo

Interventions

Perhexiline DRUG

perhexiline maleate, oral, 25mg or 100mg tablets Whenever initiating PHM therapy, subjects will receive a loading regimen of PHM as indicated in in the Heart Metabolics Dose Justification document. Drug levels will be measured first on Day 4 +/- 1 day, with an initial dose adjustment performed on Day 7 +/- 1 day, as needed. The next sampling will occur on Day 21 +/- 1 day for potential dose adjustment, as advised by the DCC, on or about Day 24. Subsequent dosing will be monitored and advised by a Dose Control Center

Intervention

Placebo DRUG

Placebo

Eligibility Criteria

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

You may qualify if:

• General Criteria
• Adult, at least 18 years of age
• Able and willing to give written informed consent Cardiomyopathy-related Criteria
• Hypertrophic cardiomyopathy (HCM) with moderate-to-severe heart failure as defined as meeting all of the following criteria:
• HCM meeting the 2011 ACCF/AHA Criteria for the Diagnosis of Hypertrophic Cardiomyopathy (Gersh et al. 2011)
• Left ventricular hypertrophy (LVH) with maximum LV wall thickness \> 15 mm by echocardiography or cardiac magnetic resonance imaging without an alternative explanation
• Left ventricular ejection fraction (LVEF) \> 40%
• Able to perform exercise testing but unable to exceed 75% of the predicted age-adjusted maximum level(as determined by METs achieved during exercise testing-eligibility is not based on VO2max)
• Normal sinus rhythm at Screening and Baseline (atrial fibrillation pattern acceptable for subjects with known chronic atrial fibrillation)
• If taking any medications for the treatment of HCM (including beta-blockers, calcium channel blockers, disopyramide, diuretics), the medication has been taken a stable dose for at least 60 days prior to enrollment and will be continued at the same dose throughout the study

You may not qualify if:

• General Criteria
• Pregnant women, women who intend to become pregnant, or woman who are not practicing contraception, either pharmacologically or with a barrier method
• Lactating women
• CYP2D6 Poor Metabolizer (PM) status, based on genotype known prior to Screening, or as predicted by genotype assessed at Screening CYP2D6 Poor Metabolizer (PM) status is defined as having no functional CYP2D6 alleles by genotyping (exclusively having allele combinations of \*3, \*4, \*5, \*6, \*7, \*8, \*12, \*14).
• Any subject who regularly takes a medication known to be a strong inhibitor of CYP2D6 (bupropion, fluoxetine, paroxetine, quinidine, or ritonavir)
• Any concomitant disease, condition, or treatment that could interfere with the conduct of the study, or that would, in the opinion of the investigator or sponsor, pose an unacceptable risk to subjects and/or interfere with the interpretation of study data, including but not limited to:
• History of a known toxic or inflammatory peripheral neuropathy, such as mononeuritis multiplex, acute or chronic inflammatory demyelinating polyneuropathy (AIDP or CIDP), axonal sensorimotor neuropathies, drug-related neuropathy or neuritis, or diabetic neuropathy (history of a compression neuropathy, such as carpal tunnel syndrome, is acceptable)
• Poorly controlled diabetes mellitus (e.g., HbA1c \> 8.5%)
• Clinically severe chronic obstructive pulmonary disease (i.e. COPD requiring home oxygen or history of IV or oral steroid use)
• History of a known chronic liver disease including cirrhosis of any cause, or chronic hepatitis B or hepatitis C
• History of porphyria
• History of recurrent hypoglycemia
• Active infection requiring antibiotics
• Life expectancy of less than 2 years
• Evidence of an active or suspected cancer or a history of malignancy, except for skin squamous cell or basal cell carcinomas that did not require systemic therapy and are considered to be cured

Sponsors & Collaborators

• Heart Metabolics Limited: lead

MeSH Terms

Conditions

Cardiomyopathy, Hypertrophic

Interventions

Perhexiline

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2015
• First Posted: April 30, 2015
• Primary Completion: July 1, 2017
• Last Updated: July 14, 2017

Record last verified: 2017-07