Trial Outcomes & Findings for Open-Label Study of Perhexiline in Patients With Hypertrophic Cardiomyopathy and Moderate to Severe Heart Failure (NCT NCT02862600)
NCT ID: NCT02862600
Last Updated: 2017-08-31
Results Overview
At the conclusion of 16 weeks of perhexiline treatment, MVO2 was measured using CPEX and compared to MVO2 measured at baseline.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
35 participants
Primary outcome timeframe
end of Period 2 (Week 16)
Results posted on
2017-08-31
Participant Flow
Fifty subjects were screened at 13 US centers. Of these, 36 were found suitable for enrollment, and 35 were enrolled prior to study termination.
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.
Participant milestones
| Measure |
Perhexiline
Perhexiline: Period 1 (Weeks 1-8) and Period 2 (Weeks 9-16): dose titrated to two different plasma levels of perhexiline
|
|---|---|
|
Period 1--Perhexiline-low Target Range
STARTED
|
35
|
|
Period 1--Perhexiline-low Target Range
COMPLETED
|
22
|
|
Period 1--Perhexiline-low Target Range
NOT COMPLETED
|
13
|
|
Period 2--Perhexiline-high Target Range
STARTED
|
22
|
|
Period 2--Perhexiline-high Target Range
COMPLETED
|
15
|
|
Period 2--Perhexiline-high Target Range
NOT COMPLETED
|
7
|
Reasons for withdrawal
| Measure |
Perhexiline
Perhexiline: Period 1 (Weeks 1-8) and Period 2 (Weeks 9-16): dose titrated to two different plasma levels of perhexiline
|
|---|---|
|
Period 1--Perhexiline-low Target Range
Lack of Efficacy
|
9
|
|
Period 1--Perhexiline-low Target Range
Protocol Violation
|
3
|
|
Period 1--Perhexiline-low Target Range
Withdrawal by Subject
|
1
|
|
Period 2--Perhexiline-high Target Range
Lack of Efficacy
|
7
|
Baseline Characteristics
Open-Label Study of Perhexiline in Patients With Hypertrophic Cardiomyopathy and Moderate to Severe Heart Failure
Baseline characteristics by cohort
| Measure |
Perhexiline
n=35 Participants
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.
|
|---|---|
|
Age, Continuous
|
50 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
33 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
29 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
35 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.
Outcome measures
| Measure |
Perhexiline--16 Weeks
n=15 Participants
Subjects completing 8 weeks of perhexiline at target range 100-300 ng/ml, and an additional 8 weeks of perhexiline at target range 300-500 ng/ml.
|
|---|---|
|
Change From Baseline of VO2MAX at 16 Weeks
|
-0.2 ml/kg/min
Standard Deviation 2.7
|
SECONDARY outcome
Timeframe: end of Period 1 (Week 8)At the conclusion of 8 weeks of perhexiline treatment, MVO2 was measured using CPEX and compared to MVO2 measured at baseline.
Outcome measures
| Measure |
Perhexiline--16 Weeks
n=22 Participants
Subjects completing 8 weeks of perhexiline at target range 100-300 ng/ml, and an additional 8 weeks of perhexiline at target range 300-500 ng/ml.
|
|---|---|
|
Change From Baseline of VO2MAX at End of Period 1
|
0.3 ml/kg/min
Standard Deviation 1.8
|
SECONDARY outcome
Timeframe: end of Period 2 (Week 16)At the conclusion of 16 weeks of perhexiline treatment, 6MWD was measured and compared to 6MWD measured at baseline.
Outcome measures
| Measure |
Perhexiline--16 Weeks
n=15 Participants
Subjects completing 8 weeks of perhexiline at target range 100-300 ng/ml, and an additional 8 weeks of perhexiline at target range 300-500 ng/ml.
|
|---|---|
|
Change From Baseline in the Six-minute Walk Test at the End of Period 2
|
27 meters
Standard Deviation 46
|
SECONDARY outcome
Timeframe: end of Period 1 (Week 8)At the conclusion of 8 weeks of perhexiline treatment, 6MWD was measured and compared to 6MWD measured at baseline.
Outcome measures
| Measure |
Perhexiline--16 Weeks
n=22 Participants
Subjects completing 8 weeks of perhexiline at target range 100-300 ng/ml, and an additional 8 weeks of perhexiline at target range 300-500 ng/ml.
|
|---|---|
|
Change From Baseline in the Six-minute Walk Test at the End of Period 1
|
16 meters
Standard Deviation 50
|
Adverse Events
Perhexiline
Serious events: 5 serious events
Other events: 19 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Perhexiline
n=35 participants at risk
All enrolled subjects
|
|---|---|
|
Musculoskeletal and connective tissue disorders
Non-cardiac chest pain
|
2.9%
1/35 • Adverse events were collected from the time of enrollment (Day 0) until 30 days after study drug termination.
|
|
Cardiac disorders
Exacerbation of congestive heart failure
|
2.9%
1/35 • Adverse events were collected from the time of enrollment (Day 0) until 30 days after study drug termination.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
2.9%
1/35 • Adverse events were collected from the time of enrollment (Day 0) until 30 days after study drug termination.
|
|
Cardiac disorders
atrial fibrillation recurrence
|
2.9%
1/35 • Adverse events were collected from the time of enrollment (Day 0) until 30 days after study drug termination.
|
|
Cardiac disorders
recurrence of atrial fibrillation
|
2.9%
1/35 • Adverse events were collected from the time of enrollment (Day 0) until 30 days after study drug termination.
|
Other adverse events
| Measure |
Perhexiline
n=35 participants at risk
All enrolled subjects
|
|---|---|
|
General disorders
Fatigue
|
11.4%
4/35 • Adverse events were collected from the time of enrollment (Day 0) until 30 days after study drug termination.
|
|
Gastrointestinal disorders
Nausea
|
8.6%
3/35 • Adverse events were collected from the time of enrollment (Day 0) until 30 days after study drug termination.
|
|
General disorders
Influenza like illness
|
8.6%
3/35 • Adverse events were collected from the time of enrollment (Day 0) until 30 days after study drug termination.
|
|
Infections and infestations
Nasopharyngitis
|
8.6%
3/35 • Adverse events were collected from the time of enrollment (Day 0) until 30 days after study drug termination.
|
|
Nervous system disorders
Dizziness
|
5.7%
2/35 • Adverse events were collected from the time of enrollment (Day 0) until 30 days after study drug termination.
|
|
Nervous system disorders
Headache
|
5.7%
2/35 • Adverse events were collected from the time of enrollment (Day 0) until 30 days after study drug termination.
|
|
Psychiatric disorders
Insomnia
|
8.6%
3/35 • Adverse events were collected from the time of enrollment (Day 0) until 30 days after study drug termination.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.7%
2/35 • Adverse events were collected from the time of enrollment (Day 0) until 30 days after study drug termination.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
5.7%
2/35 • Adverse events were collected from the time of enrollment (Day 0) until 30 days after study drug termination.
|
Additional Information
Mark G. Midei, MD, Executive Director and Head of Cardiology
Heart Metabolics, Ltd.
Phone: 4103715357
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place