A Randomized Placebo Controlled Study to Show That Rasagiline May Slow Disease Progression for Parkinson's Disease

Study Overview
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Brief Summary
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A 2 phase study to evaluate disease progression in Parkinson's disease patients taking rasagiline

Official Title
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A Multi Center, Double Blind, Randomized Start, Placebo-Controlled, Parallel-Group Study to Assess Rasagiline as a Disease Modifying Therapy in Early Parkinson's Disease Subjects

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Rasagiline Mesylate
* Drug: Rasagiline Mesylate
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women with idiopathic PD whose diagnosis is confirmed at screening, with at least two cardinal signs without any other known or suspected cause of parkinsonism. If tremor is not present, subjects must have unilateral onset and persistent asymmetry. Subjects with a diagnosis of early idiopathic PD of less than 1½ years duration from time of documented diagnosis. Subjects whose clinical condition at the time of enrollment does not require anti-PD treatment and will not require for the next 9 months. Willing and able to give informed consent. Exclusion Criteria: Subjects younger than 30 or older than 80 years. Subjects with loss of postural reflexes. Subjects with UPDRS Tremor score of 3 or greater in any limb. Subjects with Hoehn &Yahr Stage III or greater at screening. Subjects with freezing while walking. Subjects with any of the following features that tend to exclude PD as the cause of Parkinsonism: History of repeated strokes with stepwise progression of Parkinsonian features History of repeated head injury or history of definite encephalitis Sustained remission Supranuclear gaze palsy Cerebellar signs Early severe autonomic involvement Babinski's sign Presence of a cerebral tumour or communicating hydrocephalus MPTP exposure Oculogyric crises Subjects who have had previous use of rasagiline or selegiline Subjects having used other anti-PD medication basis at any time prior to baseline Subjects having used other anti-PD medication (including anticholinergics) for less than 3 weeks during the 3 month period prior to baseline. (not including a single L-Dopa dose as part of L-Dopa test) Subjects having used any other anti-PD medication (including anticholinergics) for less than 3 weeks prior to the 3 month period preceding baseline whose anti-PD medication is intentionally ceased in order for the subject to enter the study. Subjects who have a clinically significant or unstable medical or surgical condition that may preclude safe and complete participation Hypertensive subjects whose BP is not well controlled according to the medical record or as observed during the week of home BP recording prior to baseline Subjects diagnosed with melanoma based on the screening dermatologic examination, or with a history of melanoma. Subjects with suspicious lesions at baseline who do not undergo biopsy Subjects with significant cognitive impairment as defined by MMSE score < 26 Subjects with clinically significant psychiatric illness, including major depression [Beck Depression Inventory (short form) ≥15 Subjects with a history of alcohol or substance abuse within the past 2 years Subjects who have taken any experimental medications within 60 days prior to baseline Subjects who have used coenzyme Q10 (in daily doses > 300 mg) within 120 days prior to baseline Subjects who have used sympathomimetics (including over-the-counter remedies - nasal or oral), dextromethorphan, pethidine or St. John's Wort within the 7 days prior to baseline Subjects who have used antidepressants within 42 days prior to baseline Subjects who have used ciprofloxacin, a potent CYP 1A2 inhibitor within 7 days prior to baseline Subjects who have used MAO inhibitors including reserpine or methyldopa within the three months prior to baseline, or treatment with an anti-emetic or antipsychotic medication with central dopamine antagonist activity within the six months prior to baseline Women who are not postmenopausal, surgically sterilized, or using adequate birth control [oral birth control pills, IUD, or a long acting injectable form of contraception; barrier methods alone (i.e., condom) are not sufficient]. Women of childbearing potential without a negative pregnancy test at screening. Nursing women

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1mg rasagiline<br>1mg early start active treatment arm (72 weeks active)followed by 1mg 36 week delayed start active treatment arm (36 weeks placebo followed by 36 weeks active) | Drug: Rasagiline Mesylate<br>* tablet, 1mg once daily<br>|
| Experimental: 2mg rasagiline<br>2mg early start active treatment arm (72 weeks active)followed by 2mg 36 week delayed start active treatment arm (36 weeks placebo followed by 36 weeks active) | Drug: Rasagiline Mesylate<br>* tablet, 2mg once daily<br>|
| Placebo Comparator: Placebo<br>Each arm is followed by 36 weeks of placebo | Other: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Unified Parkinson's Disease Rating Scale (UPDRS) Score From Baseline | The primary efficacy endpoint was defined as the change in Total UPDRS from Baseline. Subjects were assessed according to the United Parkinson's Disease Rating Scale (UPDRS,(version 3;) Parts I and II are historical data and are designed to rate mentation, behavior and mood; Part III is done as a motor examination at the time of a visit. The UPDRS measures patient status on a scale 0, which is normal or none, to 4, which is severe or the worst scenario. | 12w, 24w, 36w, 42w, 48w, 54w, 60w, 66w, 72w | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Unified Parkinson's Disease Rating Scale (UPDRS) Score From Baseline to Last Observed Value in the Placebo Phase | Subjects were assessed according to the United Parkinson's Disease Rating Scale UPDRS,(version 3;) Parts I and II are historical data and are designed to rate mentation, behavior and mood; Part III is done as a motor examination at the time of a visit. The UPDRS measures patient status on a scale 0, which is normal or none, to 4, which is severe or the worst scenario. | 36 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's, Rasagiline Mesylate