Clinical Trial of Rasagiline in Levodopa-Treated Parkinson's Disease Patients With Motor Fluctuations

Study Overview
=================
Brief Summary
-----------------
The objective of this study is to evaluate the efficacy, tolerability, and safety of rasagiline compared to placebo in PD patients with motor fluctuations on levodopa therapy.

Detailed Description
-----------------
Levodopa has been the mainstay therapy for PD for decades, and it is considered to be one of the most effective medications for relief of the symptoms of PD. However, within few months to few years the majority of levodopa-treated patients notice a decline in the duration of benefit of each dose and develop motor-complications. A major problem is the appearance of fluctuations in mobility, cycles of ON and OFF periods. The administration of rasagiline, a MAO-B inhibitor, can slow the elimination of the endogenous dopamine supplies or the dopamine produced from the exogenous levodopa therapy and may therefore improve ON-OFF fluctuations. The objective of this study is to evaluate the efficacy, tolerability, and safety of rasagiline compared to placebo in PD patients with motor fluctuations on levodopa therapy.

Official Title
-----------------
Evaluation for the Efficacy,Tolerability,and Safety of Rasagiline in Levodopa-treated PD Patients With Motor Fluctuations: A Multicenter, Double Blind, Randomized, Placebo-Controlled Group Study (China)

Conditions
-----------------
Parkinson´s Disease

Intervention / Treatment
-----------------
* Drug: Rasagiline
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with idiopathic PD Patients receiving at least 300 mg daily doses of levodopa and not less than 8 daily doses of levodopa with the stable dose Patient with a Modified Hoehn and Yahr stage between 2 to 4 in the OFF state Patient with motor fluctuations averaging at least 2 hour daily in the OFF state Patients who have demonstrated the ability to keep accurate 24-hour diaries Exclusion Criteria: Patients with Parkinsonian syndrome induced by medicine, metabolic disease, Encephalitis and central nervous system degenerative diseases or Disease of basal ganglia Patients with severe cognitive impairment judged by a Mini Mental State Examination Patients with a clinically significant psychiatric illness Patients with Hamilton Depression Rating Scale (HAMD): total score ≤10 Patients with a clinically significant or unstable medical or surgical condition which would preclude safe and complete study participation Patients with a clinically significant or unstable vascular disease Patients with severe disabling dyskinesias Other inclusion and exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rasagiline<br>Rasagiline 0.5 mg by mouth every day for 2 weeks, then 1 mg by mouth every day for 12 weeks, then switch to 0.5mg by mouth every day for remainder of the study (approximately 16 weeks total) | Drug: Rasagiline<br>* Tablets, qd<br>* Other names: Azilect;|
| Placebo Comparator: Placebo<br>placebo 0.5 mg by mouth every day for two weeks, then 1 mg by mouth every day for 12 weeks, then switch to 0.5mg by mouth every day for remainder of the study (approximately 16 weeks total) | Drug: Placebo<br>* Tablets, qd<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of rasagiline vs placebo as assessed by the change from baseline to week 14 in mean total daily OFF time measured by patients' home diaries in levodopa-treated PD patients with motor fluctuations. |  | 0, 14 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to week 6/10/16 in mean total daily OFF time measured by patients' home diaries. |  | 0, 6, 10, 16 weeks | 
| Change from baseline to week 6/14/16 in mean total daily ON time measured by patients' home diaries. |  | 0, 6, 14, 16 weeks | 
| Change from baseline to week 6/14/16 on Unified Parkinson's Disease Rating Scale (UPDRS) Ⅱ- Ⅵ Activities of Daily Living. |  | 0, 6, 14, 16 weeks | 
| Change from baseline to week 6/10/14/16 in mean total daily ON time measured by patients' home diaries. |  | 0, 6, 10, 14, 16 weeks | 
| Analysis of the changing rate of the UPDRSⅡ -Ⅵ after treatment of week 6/14/16. |  | 0, 6, 14, 16 weeks | 
| The rate of patients whose Levodopa dose is adjusted after 6/14/16 weeks of treatment. |  | 0, 2, 6, 14, 16 weeks | 
| BP、 temperature、 breath and heart rate after 5 minutes of stasis. |  | -2, 0, 2, 6, 10, 14, 16 weeks | 
| Physical examination. |  | -2, 16 weeks | 
| Adverse Events: the occurrence of melanoma. |  | 0, 2, 6, 10, 14, 16 weeks | 
| Grade of UPDRS I |  | 0, 6, 14, 16 weeks | 
| Blood routine、 urine routine、 ALT、 AST、 TBiL、 γ-GTP、 ALP、 BUN、 Cr、 ECG. |  | 0, 6, 16 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Motor fluctuations, Parkinson´s Disease, Rasagiline