A Phase 2a, Double-blind, Randomized, Placebo-controlled, Crossover Study to Evaluate the Safety and Efficacy of AVP-923 (Dextromethorphan/Quinidine) in the Treatment of Levodopa-induced Dyskinesia in Parkinson's Disease Patients.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 14
- 主要终点
- Least Squares Mean Dyskinesia Severity Area Under the Curve (AUC) Score As Assessed By Modified Movement Disorder Society-Unified Dyskinesia Rating Scale (MDS-UDysRS) Part 3
研究概览
简要总结
To evaluate the efficacy, safety, and tolerability of AVP-923 capsules containing 45 mg dextromethorphan and 10 mg quinidine (AVP-923-45) compared to placebo for the treatment of levodopa-induced dyskinesia (LID) in patients with Parkinson's disease (PD).
详细描述
Proof-of-concept phase 2a, double-blind, randomized, placebo-controlled, crossover study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females 30 to 80 years of age, inclusive.
- •Diagnosis of idiopathic PD meeting the United Kingdom Parkinson's disease Society Brain Bank criteria.
- •Levodopa-induced dyskinesia present greater than 25% of the day as per MDS-UPDRS.
- •Dyskinesia of at least moderate severity as per MDS-UPDRS
- •Amantadine and Monoamine Oxidase (MAO) inhibitors must be discontinued at least three weeks prior to randomization.
- •Subjects currently receiving anti-parkinsonian medications, including all Levodopa preparations are eligible provided they have been on a stable dose of these medications for at least 1 month prior to randomization.
- •Concomitant use of antidepressants such as selective serotonin reuptake inhibitors are allowed, provided the dose has been stable for at least 1 month prior to randomization.
排除标准
- •Subject had a prior surgery for PD except Deep Brain Stimulation (Deep Brain Stimulation must not have been performed within one year of screening)
- •Hoehn and Yahr score of 5 when "off".
- •Subject with Cognitive impairment and/or history of psychiatric manifestations or active hallucinations.
- •Subjects with any history of complete heart block, QTc prolongation, or torsades de pointes.
- •Subjects with any family history of congenital QT interval prolongation syndrome.
- •Subjects with history of postural syncope, or any history of unexplained syncope within the last 12 months.
- •Subjects with a history of substance and/or alcohol abuse within the past 2 years.
研究组 & 干预措施
AVP-923-45
AVP-923-45 twice daily for 14 days
干预措施: AVP-923-45 (Drug)
Placebo
Placebo twice a day for 14 days
干预措施: Placebo (Drug)
结局指标
主要结局
Least Squares Mean Dyskinesia Severity Area Under the Curve (AUC) Score As Assessed By Modified Movement Disorder Society-Unified Dyskinesia Rating Scale (MDS-UDysRS) Part 3
时间窗: Over the 2-hour levodopa infusion period on the last day of each treatment period (Day 14 and Day 42)
The MDS-UDysRS was developed to evaluate involuntary movements often associated with treated Parkinson's disease (PD). Levodopa-Induced Dyskinesia severity was assessed via video analysis by unbiased blinded central raters, and was calculated using the Intensity Scale from Part 3 of the MDS-UDysRS. The Intensity Scale was made up of seven body parts: face, neck, right arm/shoulder, left arm/shoulder, trunk, right leg/hip, and left leg/hip. Each body part was scored on a variety of disability items (communication, drinking, and ambulation \[walking\]) on a scale of 0 (normal) to 4 (incapacitating dyskinesia) with a maximum total score of 28. For each body part, the highest disability score was summed to calculate the intensity score. A score of '0' was assigned to questions associated with the dressing task which were not performed due to the placement of the treatment infusion (IV) line. A higher score indicated more severe symptoms.
次要结局
- Least Squares Mean Motor Movement Area Under the Curve Score As Assessed by Modified Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III(Over the 2-hour levodopa infusion period on the last day of each treatment period (Day 14 and Day 42))
- Change From Baseline in PD Motor Diary Ratings Of Duration Of "On-time Without Bothersome Dyskinesia"(Baseline; Post-Baseline (Days 14 and 42))
- Change From Baseline in Parkinson's Disease Questionnaire-39 (PDQ-39) Domain Scores at the End of Each Treatment Period(Baseline; Post-Baseline (Day 14 or 42))
- Change From Baseline in PDQ-39 Single Index (PDQ-39-SI) Scores at the End of Each Treatment Period(Baseline; Post-Baseline (Day 14 or 42))
- Change From Screening in the Montreal Cognitive Assessment (MoCA) Calculated Score at the End of Each Treatment Period(Screening (Day -28); End of each treatment period (Days 14 or 42))
- Change From Baseline in MDS-UPDRS Scores for Part I, II, and IV(Baseline (Day 1); Post-Baseline (Day 14 or 42))
- Least Squares Mean Disability Area Under the Curve (AUC) Score As Assessed By Modified Movement Disorder Society-Unified Dyskinesia Rating Scale (MDS-UDysRS) Part 4(Over the 2-hour levodopa infusion period on the last day of each treatment period (Day 14 and Day 42))
- Least Squares Mean Timed Finger Tapping Area Under the Curve (AUC) Score(Over the 2-hour levodopa infusion period on the last day of each treatment period (Day 14 and Day 42))
- Change From Baseline in MDS-UDysRS Scores for Part 1 and 2(Baseline (Day 1); Post-Baseline (Day 14 or 42))
- Change From Baseline in the Dyskinesia and Other PD Symptoms Score As Assessed by Patient Global Impression of Change (PGIC)(Baseline; Post-Baseline (Days 14 and 42))