Phase II, Double Blind, Randomized, Placebo Controlled, Parallel Group, Trial to Explore the Potential Anti-dyskinetic Properties of CPL500036 (PDE10A Inhibitor) in Patients with Parkinson's Disease Suffering from Levodopa Induced Dyskinesia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 105
- 试验地点
- 16
- 主要终点
- Change from baseline in total UDysRS score at Week 4.
研究概览
简要总结
The aim of the study is to determine potential anti-dyskinetic properties of CPL500036 (PDE10A inhibitor) in Parkinson disease patients suffering from levodopa Induced dyskinesia. The study is to determine the efficacy and dose response of two CPL500036 doses, compared with placebo.
详细描述
This is a double-blind, randomized, placebo-controlled, parallel-group, dose ranging study, to explore the efficacy, safety, tolerability and pharmacokinetic (PK) of low and high dose of CPL500036 an phosphodiesterase 10A (PDE10A) inhibitor in Parkinson's disease patients with levodopa induced dyskinesia (LID) when administered for 28 days. The study will be conducted at multiple Clinical Sites. Approximately 108 patients will be randomized at 1:1:1 ratio to receive low or high dose of CPL500036 or placebo in a blinded manner, once daily for 28 days (Day 1 to Day 28). The study will comprise of Screening, Baseline (a 4-day in-house period), a Treatment Period and a Follow-Up Period. The patients will be discharged from clinical units during the Treatment Period. Approximately 30% of the patients (11 patients in each of the 3 treatment groups) will undergo extensive PK blood sampling during the Treatment Period and the remaining 70% of the patients will undergo sparse PK blood sampling. Patients from extensive PK blood sampling will be discharged from the Clinical Site on Day 8 and Day 1 for patients from sparse PK blood sampling group respectively.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 50 Years 至 80 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
CPL500036 low dose
Patients will receive 20 mg of CPL500036 administered once daily for 28-days treatment period.
干预措施: CPL500036 - low dose (Drug)
CPL500036 high dose
Patients will receive 40 mg of CPL500036 administered once daily for 28-days treatment period.
干预措施: CPL500036 - high dose (Drug)
Placebo
Patients will receive placebo administered once daily for 28-days treatment period.
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline in total UDysRS score at Week 4.
时间窗: Day -1, Day 28
Determination of the effect of low and high dose of CPL500036 compared to placebo, on the reduction of dyskinesia based on Unified Dyskinesia Rating Scale (UDysRS). The UDysRR scale is used to measure dyskinesia in Parkinson disease. Within a single scale, rater is to evaluate patient perceptions, time factors, anatomical distribution, objective impairment, severity, and disability which are accordingly divided into Part 1, Part 2, Part 3 and Part 4 of the UDysRS scale, respectively.
次要结局
- Change from baseline in UDysRS objective sub-scale scores Part 3 and 4.(Day -1, Week 1, 2, 3 and 4)
- Change from baseline in MDS-UPDRS total score at Week 4(Day -1, Day 28)
- Tmax - time to reach maximum CPL500036 concentration(up to 24 hours post administration on Day 1 and Day 7)
- Number of abnormal clinically significant findings (physical, neurological, ophthalmological and dermatological examinations).(Up to 6 weeks)
- Cmax - maximum CPL500036 plasma concentration(up to 24 hours post administration on Day 1 and Day 7)
- AUC(0-inf) - area under the plasma concentration - time curve from time 0 to infinity time for CPL500036(up to 24 hours post administration on Day 1 and Day 7)
- Apparent clearance (CL/F) for CPL500036 compound(up to 24 hours post administration on Day 1 and Day 7)
- Adverse events assessment(up to 6 weeks)
- Kel - terminal elimination rate constant(up to 24 hours post administration on Day 1 and Day 7)
- Number of abnormal clinically significant findings in clinical laboratory assessments (hematology, coagulation, clinical chemistry, urinalysis).(Up to 6 weeks)
- Number of abnormal clinically significant findings in vital signs assessments (respiratory, body temperature, blood pressure, pulse).(Up to 6 weeks)
- AUC(0-24) - area under the plasma concentration - time curve from time 0 to 24 hours after IMP administration for CPL500036(up to 24 hours post administration on Day 1 and Day 7)
- C(trough) - CPL500036 concentration before dosing(Day 1 and Day 7)
- Change from baseline in MDS-UPDRS Part 4/A scores at Week 4(Day -1, Day 28)
- Change from baseline in Hauser Subject Diary data in ON time with and without dyskinesia or with non-troublesome dyskinesia.(up to 6 weeks)
- Apparent terminal elimination half-life (T1/2) for CPL500036 compound(up to 24 hours post administration on Day 1 and Day 7)
- Change from baseline in inflammatory cytokines level at Week 4(Day 1, Day 28)
- Apparent volume of distribution during the terminal phase (Vz/F) for CPL500036 compound(up to 24 hours post administration on Day 1 and Day 7)
- Number of abnormal clinically significant findings in electrocardiogram results.(Up to 6 weeks)