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Lack of Efficacy
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Perhexiline | Drug | Period 1 (Weeks 1-8) and Period 2 (Weeks 9-16): dose titrated to two different plasma levels of perhexiline |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | end of Period 2 (Week 16) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | end of Period 1 (Week 8) |
| Change From Baseline in the Six-minute Walk Test at the End of Period 2 |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mark Midei, MD | Heart Metabolics | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford | California | United States | ||||
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The principal reason for screen failure was attainment of > 75% of the maximum predicted MVO2 on CPEX testing. One subject was found to be a CYP2D6 poor metabolizer.
Fifty subjects were screened at 13 US centers. Of these, 36 were found suitable for enrollment, and 35 were enrolled prior to study termination.
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| ID | Title | Description |
|---|---|---|
| FG000 | Perhexiline | Perhexiline: Period 1 (Weeks 1-8) and Period 2 (Weeks 9-16): dose titrated to two different plasma levels of perhexiline |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Period 1--Perhexiline-low Target Range |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 2, 2016 | Jul 5, 2017 |
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Open-label, 2 period, dose escalation study of perhexiline in symptomatic patients with hypertrophic cardiomyopathy
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| Use of bioanalytical assay to monitor plasma levels of perhexiline | Device | 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. |
|
At the conclusion of 16 weeks of perhexiline treatment, 6MWD was measured and compared to 6MWD measured at baseline. |
| 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. | end of Period 1 (Week 8) |
| Indianapolis |
| Indiana |
| United States |
| Johns Hopkins | Baltimore | Maryland | United States |
| University of Maryland | Baltimore | Maryland | United States |
| Detroit | Michigan | United States |
| Columbus | Ohio | United States |
| Portland | Oregon | United States |
| Hershey | Pennsylvania | United States |
| Germantown | Tennessee | United States |
| Salt Lake City | Utah | United States |
| Madison | Wisconsin | United States |
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| COMPLETED | Period and study terminated |
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| NOT COMPLETED |
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| Period 2--Perhexiline-high Target Range |
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Baseline data was collected on all enrolled subjects on Day 0.
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| ID | Title | Description |
|---|---|---|
| BG000 | Perhexiline | 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. Perhexiline: 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 perhexiline: 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | ml/kg/min | end of Period 2 (Week 16) |
|
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| ||||||||||||||||||||||||||
| Secondary | 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. | Posted | Mean | Standard Deviation | ml/kg/min | end of Period 1 (Week 8) |
|
| |||||||||||||||||||||||||||
| Secondary | 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. | Posted | Mean | Standard Deviation | meters | end of Period 2 (Week 16) |
|
| |||||||||||||||||||||||||||
| Secondary | 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. | Posted | Mean | Standard Deviation | meters | end of Period 1 (Week 8) |
|
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Adverse events were collected from the time of enrollment (Day 0) until 30 days after study drug termination.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Perhexiline | All enrolled subjects | 0 | 35 | 5 | 35 | 19 | 35 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Non-cardiac chest pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| Exacerbation of congestive heart failure | Cardiac disorders | Non-systematic Assessment | The subject had a history of CHF which was exacerbated during the study. The investigator classified the event as unrelated to study drug. |
| |
| Pneumonia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| atrial fibrillation recurrence | Cardiac disorders | Non-systematic Assessment | A subject with a history of AF had a recurrent event during the trial. The subject was admitted and the condition resolved. The investigator classified the event as unrelated to study drug. |
| |
| recurrence of atrial fibrillation | Cardiac disorders | Non-systematic Assessment | A subject with a history of AF had a recurrent event during the trial. The subject was admitted and the condition resolved. The investigator classified the event as unrelated to study drug. |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | Non-systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| Influenza like illness | General disorders | Non-systematic Assessment |
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| Nasopharyngitis | Infections and infestations | Non-systematic Assessment |
| ||
| Dizziness | Nervous system disorders | Non-systematic Assessment |
| ||
| Headache | Nervous system disorders | Non-systematic Assessment |
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| Insomnia | Psychiatric disorders | Non-systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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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.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Mark G. Midei, MD, Executive Director and Head of Cardiology | Heart Metabolics, Ltd. | 4103715357 | 410 | markgmidei@gmail.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 1, 2017 | Jul 5, 2017 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 13, 2016 | Jul 5, 2017 | ICF_002.pdf |
| ID | Term |
|---|---|
| D002312 | Cardiomyopathy, Hypertrophic |
| D024741 | Cardiomyopathy, Hypertrophic, Familial |
| D006333 | Heart Failure |
| ID | Term |
|---|---|
| D009202 | Cardiomyopathies |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001020 | Aortic Stenosis, Subvalvular |
| D001024 | Aortic Valve Stenosis |
| D000082862 | Aortic Valve Disease |
| D006349 | Heart Valve Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| D010480 | Perhexiline |
| ID | Term |
|---|---|
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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