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
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 35
- 试验地点
- 2
- 主要终点
- Change From Baseline of VO2MAX at 16 Weeks
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Perhexiline (Drug)
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.
干预措施: Use of bioanalytical assay to monitor plasma levels of perhexiline (Device)
结局指标
主要结局
Change From Baseline of VO2MAX at 16 Weeks
时间窗: 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.
次要结局
- Change From Baseline of VO2MAX at End of Period 1(end of Period 1 (Week 8))
- Change From Baseline in the Six-minute Walk Test at the End of Period 2(end of Period 2 (Week 16))
- Change From Baseline in the Six-minute Walk Test at the End of Period 1(end of Period 1 (Week 8))