Cardiomyopathy, HypertrophicPhase 2NCT02862600

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

A Phase 2 study testing Perhexiline and Use of bioanalytical assay to monitor plasma levels of perhexiline in people with Cardiomyopathy, Hypertrophic and Cardiomyopathy, Hypertrophic, Familial, run by Heart Metabolics Limited at 11 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Cardiomyopathy, Hypertrophic, Cardiomyopathy, Hypertrophic, Familial
What is being tested?: Perhexiline and Use of bioanalytical assay to monitor plasma levels of perhexiline
Type of treatment: Pill or oral medicine, Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 35 participants
Where: 11 sitesUnited States
Study dates: 1 Aug 2016to 22 May 2017
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

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

Who cannot join

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

Trial locations and contacts

11 sites in 1 country.

City, postcode or hospital

11 sites in 1 country

United States11 sites

Johns Hopkins
Baltimore, Maryland
University of Maryland
Baltimore, Maryland
Study site
Columbus, Ohio
Study site
Detroit, Michigan
Study site
Germantown, Tennessee
Study site
Hershey, Pennsylvania
Study site
Indianapolis, Indiana
Study site
Madison, Wisconsin
Study site
Portland, Oregon
Study site
Salt Lake City, Utah
Study site
Stanford, California

Other trials in United States

About this study

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

Read the 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.

Conditions: Cardiomyopathy, Hypertrophic, Cardiomyopathy, Hypertrophic, Familial
Being tested: Perhexiline, Use of bioanalytical assay to monitor plasma levels of perhexiline
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
Medical subject headings: Cardiomyopathy, Hypertrophic, Cardiomyopathy, Hypertrophic, Familial, Heart Failure

What participants receive

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

PerhexilineDrug
Period 1 (Weeks 1-8) and Period 2 (Weeks 9-16): dose titrated to two different plasma levels of perhexiline
Use of bioanalytical assay to monitor plasma levels of perhexilineDevice
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 groups in NCT02862600
Study group	Role	What they receive
Perhexiline	Experimental	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. Receives: Drug: Perhexiline; Device: Use of bioanalytical assay to monitor plasma levels of perhexiline

What is being measured

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

Change From Baseline of VO2MAX at 16 Weeks
At the conclusion of 16 weeks of perhexiline treatment, MVO2 was measured using CPEX and compared to MVO2 measured at baseline.
Measured: end of Period 2 (Week 16)

Secondary outcomes (3)

Change From Baseline of VO2MAX at End of Period 1
At the conclusion of 8 weeks of perhexiline treatment, MVO2 was measured using CPEX and compared to MVO2 measured at baseline.
Measured: end of Period 1 (Week 8)
Change From Baseline in the Six-minute Walk Test at the End of Period 2
At the conclusion of 16 weeks of perhexiline treatment, 6MWD was measured and compared to 6MWD measured at baseline.
Measured: end of Period 2 (Week 16)
Change From Baseline in the Six-minute Walk Test at the End of Period 1
At the conclusion of 8 weeks of perhexiline treatment, 6MWD was measured and compared to 6MWD measured at baseline.
Measured: end of Period 1 (Week 8)

Timeline

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

1 Aug 201622 May 2017

First posted11 Aug 2016 (estimated)
Study start1 Aug 2016
Primary completion28 Apr 2017
Study completion22 May 2017

Why it stopped: Lack of Efficacy

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Cardiomyopathy, HypertrophicStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: Open-label, 2 period, dose escalation study of perhexiline in symptomatic patients with hypertrophic cardiomyopathy
Masking: None (open label)
Enrolment: 35 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02862600
Sponsor's protocol ID: HML-PHX-005
Status last verified: Aug 2017
First submitted: 8 Aug 2016
Last updated: 31 Aug 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: Yes
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Human Experimental Models of Pain (HEMP)
Acute Pain
Not yet recruiting
NHLBI SESAME (SEptal Scoring Along Midline Endocardium) Multi-Center Prospective Study Using Improvised Off-Label Devices
Hypertrophic Cardiomyopathy, Left Ventricular Outflow Obstruction
RecruitingPhase 1
Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HTX-001
Nonobstructive Hypertrophic Cardiomyopathy
Recruiting
Positron Emission Tomography to Assess the Effect of Camzyos on Ischaemia in HOCM: PEACH Trial
Hypertrophic Obstructive Cardiomyopathy \(HOCM\), Left Ventricular Outflow Tract Obstruction
RecruitingObservational study
A 10-Minute Cardiovascular Magnetic Resonance Protocol for Cardiac Disease
Coronary Artery Disease, Myocarditis

All Cardiomyopathy, Hypertrophic trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02862600
Acronym / sponsor ID: HML-PHX-005
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
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Lack of Efficacy
Enrolment: 35 participants (actual)
Lead sponsor: Heart Metabolics LimitedIndustry (pharma, biotech, devices)
Study start: 1 Aug 2016 (actual)
Primary completion: 28 Apr 2017 (actual)
Study completion: 22 May 2017 (actual)
First posted: 11 Aug 2016 (estimated)
Results: Posted 31 Aug 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Open-label, 2 period, dose escalation study of perhexiline in symptomatic patients with hypertrophic cardiomyopathy

Arm	Type	Receives
Perhexiline	Experimental	Drug: Perhexiline, Device: Use of bioanalytical assay to monitor plasma levels of perhexilinePerhexiline 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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 (7 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PerhexilinePeriod 1 (Weeks 1-8) and Period 2 (Weeks 9-16): dose titrated to two different plasma levels of perhexiline	Drug	Perhexiline
Use of bioanalytical assay to monitor plasma levels of perhexilineThe 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.	Device	Perhexiline

Primary outcome

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.

3 secondary outcomes

Change From Baseline of VO2MAX at End of Period 1
Time frame: end of Period 1 (Week 8)
Change From Baseline in the Six-minute Walk Test at the End of Period 2
Time frame: end of Period 2 (Week 16)
Change From Baseline in the Six-minute Walk Test at the End of Period 1
Time frame: end of Period 1 (Week 8)

Results and safety

Results posted to the registry on 31 Aug 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Perhexiline	35	22

Primary outcome: Change From Baseline of VO2MAX at 16 Weeks

Time frame: end of Period 2 (Week 16). Mean (Standard Deviation). Unit: ml/kg/min

Measure	Perhexiline--16 Weeks n = 15
Value	-0.2 (2.7)

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected from the time of enrollment (Day 0) until 30 days after study drug termination.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Perhexiline	5 of 35 (14.3%)	19 of 35 (54.3%)	0 of 35

Limitations and caveats (from the sponsor): Early termination due to lack of efficacy in the first 15 subjects completing the study. Any conclusions regarding safety or efficacy a challenging in light of the small numbers of subjects studied.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Cardiomyopathy, Hypertrophic

Not yet recruiting
Human Experimental Models of Pain (HEMP)
Acute Pain
Not yet recruiting
NHLBI SESAME (SEptal Scoring Along Midline Endocardium) Multi-Center Prospective Study Using Improvised Off-Label Devices
Hypertrophic Cardiomyopathy, Left Ventricular Outflow Obstruction
RecruitingPhase 1
Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HTX-001
Nonobstructive Hypertrophic Cardiomyopathy
Recruiting
Positron Emission Tomography to Assess the Effect of Camzyos on Ischaemia in HOCM: PEACH Trial
Hypertrophic Obstructive Cardiomyopathy \(HOCM\), Left Ventricular Outflow Tract Obstruction
RecruitingObservational study
A 10-Minute Cardiovascular Magnetic Resonance Protocol for Cardiac Disease
Coronary Artery Disease, Myocarditis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mark Midei, MD study chair

Heart Metabolics

11 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 4 inclusion and 7 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: stopped early, as of the sponsor's last update on 31 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Change From Baseline of VO2MAX at 16 Weeks (time frame: end of Period 2 (Week 16)). 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 NCT02862600.

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 31 Aug 2017.