- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02431221
Efficacy, Safety, and Tolerability of Perhexiline in Subjects With Hypertrophic Cardiomyopathy and Heart Failure
A Study on the Efficacy, Safety, and Tolerability of Perhexiline Maleate in Subjects With Hypertrophic Cardiomyopathy and Moderate-To-Severe Heart Failure
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Phase
- Phase 3
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
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
Exclusion Criteria:
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
- History of substance abuse, including alcohol or illicit drugs within the past 12 months
- Abnormal safety studies of clinical significance at Screening such as:
i. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, or lactate dehydrogenase > 1.5X upper limit of normal (ULN)
ii. Glucose < 70 mg/dL iii. Prolonged QTc (>450 msec) l. Known hypersensitivity to perhexiline maleate
- Unable or unwilling to comply with the protocol
Enrolled in another therapeutic trial for hypertrophic cardiomyopathy
Cardiomyopathy-related Exclusion Criteria
- Asymptomatic subjects or subjects whose symptoms are controlled with medications
- Resting LVOT gradient > 50 mmHg or known exercise-induced LVOT gradient > 80 mmHg
- Absence of an implanted, operational ICD if there is a history of frequent non-sustained ventricular tachycardia, or a first degree relative having had sudden cardiac death or ICD implant
- Known coronary artery disease (> 50% arterial luminal narrowing of a major epicardial vessel)
- History of cardiac transplantation
- Cardiac surgery or septal reduction surgery planned or having occurred within past 6 months
- HCM believed to be caused by infiltrative disorders, glycogen storage disorders, and hypertensive heart disease (including genotypic or phenotypic evidence of Fabry's Disease)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: QUADRUPLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Intervention
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.
|
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
|
PLACEBO_COMPARATOR: Placebo
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Subject Outcome Variable
Time Frame: 6 months after randomization
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Functional Assessment During Randomized Withdrawal Phase
Time Frame: 6 months after initiation of open label period, and 3 months after randomized withdrawal period initiated
|
Change of CPEX-VO2max from the beginning of the Randomized Withdrawal phase to the end of the Randomized Withdrawal phase (Part 4).
The change in CPEX-VO2max in the placebo group will be compared to the change in CPEX-VO2max in the continued perhexiline (non-withdrawal) group.
|
6 months after initiation of open label period, and 3 months after randomized withdrawal period initiated
|
Functional Assessment During Randomized Phase
Time Frame: 6 months after Randomization
|
Change in six-minute walk test (6MWT) from baseline (pre-Part 1 run-in, prior to receiving any perhexiline) to 6 months after randomization during the Randomized Treatment (Part 2)
|
6 months after Randomization
|
Functional Assessment During Randomized Withdrawal Phase
Time Frame: 6 months after initiation of open label period, and 3 months after randomized withdrawal period initiated
|
Change in six-minute walk test (6MWT) from the beginning of the Randomized Withdrawal (Part 4) to the end of the Randomized Withdrawal (Part 4)
|
6 months after initiation of open label period, and 3 months after randomized withdrawal period initiated
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Primary Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Heart Diseases
- Cardiovascular Diseases
- Pathological Conditions, Anatomical
- Aortic Valve Disease
- Heart Valve Diseases
- Aortic Stenosis, Subvalvular
- Aortic Valve Stenosis
- Heart Failure
- Hypertrophy
- Cardiomyopathies
- Cardiomyopathy, Hypertrophic
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Membrane Transport Modulators
- Calcium-Regulating Hormones and Agents
- Calcium Channel Blockers
- Perhexiline
Other Study ID Numbers
- HM-PHX-003
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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