An Open Label Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MEK162 in Noonan Syndrome Hypertrophic Cardiomyopathy
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- Change from baseline in Left ventricular mass (LVM)
研究概览
简要总结
The purpose of the study is to determine whether the ability of MEK162 to antagonize MEK activation in NS HCM patients, who usually have upstream mutations in the Ras-Raf-Mek-Erk pathway that lead to MEK activation, would be beneficial over a 6 month treatment period in hypertrophy regression.
详细描述
This study is designed as a proof of concept of MEK162 in NS HCM patients. The purpose of the present study is to determine whether the ability of MEK162 to antagonize MEK activation in NS HCM patients, who usually have upstream mutations in the Ras-Raf-Mek-Erk pathway that lead to MEK activation, would be beneficial over a 6 month treatment period by causing hypertrophy regression. Such regression might result in cardiovascular clinical benefits with longer term treatment.
The information gained from this study will be three fold:
- the safety/tolerability of treatment with MEK162 over 6 month in the NS HCM patient population
- the pharmacokinetics and pharmacodynamics of MEK162 in the target patient population
- proof of the therapeutic concept that MEK inhibition will reduce cardiac hypertrophy in the target NS HCM patient population
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
MEK162
Patients will be treated with MEK162 only and will be uptitrated or down titrated based on safety and tolerability observed.
干预措施: MEK162 (Drug)
结局指标
主要结局
Change from baseline in Left ventricular mass (LVM)
时间窗: Baseline to 3 months and 6 months
Change in LVM after 3 months and 6 months of treatment using magnetic resonance imaging.
次要结局
- Change from baseline in Cardiac energetics state at 3 months and 6 months(Baseline to 3 months and 6 months)
- Number of patients with adverse events, serious adverse events and death(6 months)
- Pharmacokinetics of MEK162 and metabolite (AR00426032): The trough plasma concentration (Ctrough) just prior to drug administration(Days 1, 8, 15, 28, 56, 84, 140 and 182)
- Pharmacokinetics of MEK162 and metabolite (AR00426032): maximum drug exposure of MEK162 and its metabolite (AR00426032) in plasma(Day 1 and Day 8)
- Pharmacokinetics of MEK162 and metabolite (AR00426032): time to reach peak concentration (Tmax) in plasma(Day 1 and Day 8)
- Pharmacokinetics of MEK162 and metabolite (AR00426032): Area under the plasma concentration-time profile from time zero to 12 hours post dose (AUC0-12h)(Day 1 and Day 8)
- Pharmacokinetics of MEK162 and metabolite (AR00426032): Area under the plasma concentration-time profile from time zero to the last quantifiable sample (AUClast)(Day 1 and Day 8)
- Pharmacokinetics of MEK162 and metabolite (AR00426032):observed maximum plasma concentration (Cmax) following drug adminstration(Day 1 and Day 8)
- Pharmacokinetics of MEK162 and metabolite (AR00426032): accumulation ratio (Racc)(Day 1 and Day 8)
- Pharmacokinetics of MEK162: The degree of fluctuation of MEK162 and its metabolite (AR00426032) in plasma at steady state (on Day 8)(Day 8)
- Pharmacokinetics of MEK162: The ratio of Metabolite (AR00426032) to MEK162 in plasma on Days 1 and 8(Day 1 and Day 8)
- Change from baseline in end systolic and end diastolic right and left vetricular volumes in 3 and 6 months(baseline to 3 and 6 months of treatment)
- Change from baseline in stroke volume and stroke output during 3 and 6 months(baseline to 3 and 6 months of treatment)
- Ejection fraction(baseline, 3 and 6 months of treatment)
- Cardiac index(baseline, 3 and 6 months of treatment)