13-week, Double-blind, Placebo-controlled, Fixed-dose, Multicenter Study to Evaluate the Efficacy and Safety of Modified Release AFQ056 in Reducing Moderate to Severe L-dopa Induced Dyskinesias in Patients With Parkinson's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 154
- 试验地点
- 1
- 主要终点
- Change in modified AIMS (Abnormal Involuntary Movement Scale) total score from baseline to Week 12
研究概览
简要总结
This study will assess the efficacy and safety of modified release AFQ056 in patients that have Parkinson's Disease L-dopa Induced Dyskinesias (PD-LID)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, 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 30-80 years old
- •Use of highly effective methods of contraception during study in women of childbearing potential
- •Outpatients
- •Clinical diagnosis of Parkinson's Disease according to UK Parkinson's Disease Society Brain Bank Clinical Diagnosis criteria
- •Score of >/= 2 on UPDRS items 32 and 33
- •Dyskinesias for at least 3 months before baseline
- •On stable treatment regimen with L-dopa and other anti-parkinsonian treatment for 4 weeks prior to baseline
- •Demonstrate capacity to complete accurate diary ratings
- •Patients who have a primary caregiver willing to assess the condition of the patient throughout the study in accordance with protocol requirements
- •Group 2 only: Patients must be on a stable and well tolerated dose of amantadine for at least 4 weeks prior to BL1 and must maintain the stable dose of amantadine during the remainder of the study
排除标准
- •Atypical/secondary form of Parkinson's disease
- •History of surgical treatment of PD, including deep brain stimulation
- •A score of 5 in the "ON"- state on the Modified Hoehn and Yahr scale
- •Advanced, severe, or unstable disease other than PD
- •Evidence of dementia
- •Treatment with certain prohibited medications
- •Amantadine within 2 weeks prior to BL1 visit (applies to Group 1 only)
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
AFQ056 150 mg
Patients randomized to the AFQ056 150 mg arm will receive AFQ056 oral tablets to be titrated until reaching the target dose of 150 mg twice daily.
干预措施: AFQ056 (Drug)
AFQ056 200 mg
Patients randomized to the AFQ056 200 mg arm will receive AFQ056 oral tablets to be titrated until reaching the target dose of 200 mg twice daily.
Patients will be randomized in two groups by amantadine status.
- Group 1: Patients are not permitted to take amantadine within 2 weeks prior to the BL1 visit.
- Group 2: Patients must be on a stable and well tolerated dose of amantadine for at least 4 weeks prior to BL1 and must maintain the stable dose of amantadine during the remainder of the study.)
干预措施: AFQ056 (Drug)
Placebo
Patients randomized to the Placebo arm will receive oral AFQ056 Placebo twice daily
干预措施: Placebo (Drug)
结局指标
主要结局
Change in modified AIMS (Abnormal Involuntary Movement Scale) total score from baseline to Week 12
时间窗: 12 weeks
The modified AIMS is a scale used to assess dyskinesia. It focuses on six different parts of the body and rates abnormal movements from 0 (absence of dyskinesia to 4 (severe) (maximal score, 24). Change from baseline to Week 12 will be analyzed using the mixed effect repeated measures model (MMRM) including treatment, pooled center, week, treatment by week interaction as fixed effects and baseline total score as covariate with an unstructured covariance structure.
The incidence rate of adverse events
时间窗: Monitored for the duration of the study which is 13 weeks
The occurrence of adverse events would be sought by non-directive questioning of the patient. Adverse events may also be detected when they are volunteered by the patient or through physical examination, laboratory test, or other assessments. AEs will be summarized by presenting, for each treatment group the number and percentage of patients having any adverse event, having an adverse event in each system organ class and having each individual adverse event by system organ class and preferred term.
The percentage of patients discontinued during the up titration period due to AE
时间窗: Assessed during the up titration period of 6 weeks
Patients randomized will be up titrated to the target doses at regular intervals during the up titration period. AEs will be summarized by presenting, for each treatment group the number and percentage of patients having any adverse event, having an adverse event in each system organ class and having each individual adverse event by system organ class and preferred term.
Time to onset of adverse events
时间窗: Monitored for the duration of the study which is 13 weeks
The occurrence of adverse events (AEs) would be sought by non-directive questioning of the patient. Adverse events may also be detected when they are volunteered by the patient or through physical examination, laboratory test, or other assessments. AEs will be summarized by presenting, for each treatment group the number and percentage of patients having any adverse event, having an adverse event in each system organ class and having each individual adverse event by system organ class and preferred term.
The percentage of patients reaching and maintaining the target dose during the fixed dose treatment period
时间窗: Assessed during the fixed dose treatment period of 6 weeks
Randomized patients will be up titrated to the target dose and remain on the target dose for the duration of the fixed dose treatment period. AEs will be summarized by presenting, for each treatment group the number and percentage of patients having any adverse event, having an adverse event in each system organ class and having each individual adverse event by system organ class and preferred term.
次要结局
- Change in Lang-Fahn Activities of Daily Living Dyskinesia Scale (LFADLDS) total score from baseline to Week 12(12 weeks)
- Change from baseline Total ON- and OFF-times and ON-time with dyskinesia and with troublesome dyskinesias (patient diary) to Week 12(12 weeks)
- Changes in vital signs from baseline to each post-baseline visit(Monitored at regular visits throughout duration of the study which is 13 weeks)
- Total scores of the Scales for Outcomes in Parkinson's disease - Psychiatric Complications (SCOPA-PC)(Assessed for 12 weeks)
- Change in clinician-rated global impression of change (CGIC) score from baseline to Week 12(12 weeks)
- Change in Mini Mental State Exam (MMSE) total scores from baseline to Week 12(12 weeks)
- Investigate the safety of concomitant administration of AFQ056 with amantadine(12 weeks)
- The change in total score and sub-score of UDysRS Parts I, II, III, and IV from baseline to Week 12(12 weeks)
- Change in score for items 32, 33 and 34 of Part IV of the Unified Parkinson's Disease Rating Scale (UPDRS ) from baseline to Week 12(12 weeks)
- Changes in hematology/blood chemistry and urinalysis laboratory evaluations from baseline to each post-baseline visit where hematology/blood chemistry and urinalysis are collected(Monitored at regular visits throughout duration of the study which is 13 weeks)
- Percentage of adverse events including treatment emergent adverse events and serious adverse events(Monitored for the duration of the study which is 13 weeks)
- Change in Unified Parkinson's Disease Rating Scale (UPDRS) Part III (Motor Examination) scores from baseline to Week 12(12 weeks)
- Change in cognitive test battery (CogState) scores form baseline to Week 12(12 weeks)
- Pharmacokinetics of AFQ056 in patients with Parkinson's disease with moderate to severe dyskinesias(Monitored at regular visits throughout duration of the study which is 13 weeks)
- Changes in electrocardiogram (ECG) from baseline to each post-baseline visit where ECGs are performed(Monitored at regular visits throughout duration of the study which is 13 weeks)
- Proportion of patients who have suicidal ideation and behavior as mapped to Columbia Classification Algorithm for Suicide assessment (C-CASA) using data from Columbia-Suicide Severity Rating Scale (C-SSRS)(This will be assessed for the duration of the study which is 13 weeks)
- Plasma Pharmacokinetics of AFQ056 in patients with Parkinson's disease with moderate to severe dyskinesias(At Week 12 or earlier if the patient discontinues the study before Week 12)