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Hypertrophic CardiomyopathyPhase 3NCT02431221

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

A Phase 3 study testing Perhexiline in people with Hypertrophic Cardiomyopathy, run by Heart Metabolics Limited.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Hypertrophic Cardiomyopathy
What is being tested?
Perhexiline
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
No sites listed yet
Study dates
Start not givento Jul 2017
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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:
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  • 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:
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, or lactate dehydrogenase > 1.5X upper limit of normal (ULN)
  • 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)

About this study

Official title: A Study on the Efficacy, Safety, and Tolerability of Perhexiline Maleate in Subjects With Hypertrophic Cardiomyopathy and Moderate-To-Severe Heart Failure

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

Read the detailed description

This study is an international, multi-center, randomized, double-blind, placebo controlled clinical trial of the effects of perhexiline maleate on a rank-ordered, hierarchical variable consisting of outcome and functional measures in 350 subjects with hypertrophic cardiomyopathy and symptoms of moderate to severe congestive heart failure. The study is designed in four parts: 1) an open-label run-in period of 2 weeks, 2) A blinded, randomized phase of variable duration (anticipated between 6 months and 18 months depending on enrollment rate), 3) an open label period of 3 months, and 4) a randomized withdrawal period of 3 months. Subjects who do not experience an adverse outcome (death or resuscitated ventricular arrhythmia, stroke, need for surgical intervention, cardiovascular hospitalization, occurrence of atrial fibrillation, or study dropout) will undergo cardiopulmonary exercise testing in order to determine change from baseline in maximum oxygen consumption.

Being tested
Perhexiline, Placebo
Keywords
perhexiline, HCM, Hypertrophic Cardiomyopathy, CPEX
Medical subject headings
Cardiomyopathy, Hypertrophic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PerhexilineDrug

    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

  • PlaceboDrug

Study groups in NCT02431221
Study groupRoleWhat they receive
InterventionExperimentalPerhexiline 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.
Receives: Drug: Perhexiline
PlaceboPlacebo comparatorPlacebo 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 6 months after randomization

Secondary outcomes (3)

  1. Functional Assessment During Randomized Withdrawal Phase

    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.

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

  2. Functional Assessment During Randomized Phase

    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)

    Measured: 6 months after Randomization

  3. Functional Assessment During Randomized Withdrawal Phase

    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)

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Apr 2015 (estimated)
  2. Primary completionJul 2017

Why it stopped: Lack of efficacy in a preceding study.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02431221
Sponsor's protocol ID
HM-PHX-003
Status last verified
Jul 2017
First submitted
27 Apr 2015
Last updated
14 Jul 2017
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Perhexiline in people with Hypertrophic Cardiomyopathy, run by Heart Metabolics Limited.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 14 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Subject Outcome Variable (time frame: 6 months after randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02431221.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2017.

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