Rasagiline as Add on to Dopamine Agonists in the Treatment of Parkinson's Disease

Study Overview
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Brief Summary
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To assess the efficacy of rasagiline 1 mg as a first add-on treatment to dopamine agonist therapy in early Parkinson Disease (PD) patients, , not optimally controlled on dopamine agonists as compared to placebo.

Official Title
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A Double-blind, Placebo Controlled, Randomized, Multicenter Study to Assess the Safety and Clinical Benefit of Rasagiline as an Add on Therapy to Stable Dose of Dopamine Agonists in the Treatment of Early Parkinson's Disease

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: Rasagiline
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: receiving stable dose of oral ropinirole or pramipexole whose symptoms are not optimally controlled or whose oral dopamine agonist titration regimen was truncated due to intolerability: 1) Minimum dose of agonist will be 6 mg/day for ropinirole and 1.0 mg/day for pramipexole 2) Stable dopamine agonist treatment must have been ongoing for ≥ 30 days, no longer than 5 years preceding baseline Males and females. Women of childbearing potential must agree to practice an acceptable method of birth control. Idiopathic Parkinson Disease confirmed at baseline by presence of at least 2 cardinal signs (resting tremor, bradykinesia, rigidity), w/o other known or suspected cause of Parkinsonism Hoehn & Yahr > 1 (symptoms on only one side of the body) with treatment and < 3 (mild to moderate bilateral disease; some postural instability; physically independent). Dopamine agonist dose must be stable for ≥30 days preceding the baseline visit. For patients who are receiving amantadine or anticholinergics, the dose must have been stable for ≥30 days prior to screening. Medically stable outpatients (Investigator's judgment). Exclusion Criteria: receive rasagiline or other monoamine oxidase (MAO) inhibitors 60 days preceding baseline receive levodopa > 21 consecutive days within 90 days prior baseline moderate to severe motor fluctuations hepatic impairment investigational medications 30 days preceding baseline dopamine agonist use > 5 years prior to baseline major depression as defined by Beck Depression Inventory (BDI) short form score greater than 14 significant cognitive impairment as defined by Mini-Mental State Exam (MMSE) score less than 26. impulse control disorder (ICD) based on the Questionnaire for Impulsive-compulsive Disorders in Parkinson's Disease form (QUIP). pregnant or lactating or planning on becoming pregnant in the next 18 weeks uncontrolled hypertension. Patients whose hypertension is controlled with medications are eligible. Concomitant monoamine oxidase (MAO) inhibitors or medicines contraindicated w/ MAO inhibitors not allowed

Ages Eligible for Study
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Minimum Age: 30 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rasagiline 1 mg<br>Participants took a 1 mg rasagiline tablet orally each day for 18 weeks. | Drug: Rasagiline<br>* 1mg tablet daily for 18 weeks<br>* Other names: AZILECT®;|
| Placebo Comparator: Placebo<br>Participants took a matching placebo tablet once daily for 18 weeks. | Drug: Placebo<br>* one tablet daily for 18 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Parts I, II and III | The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. Version 3 of UPDRS contains four parts, three of which are totaled and reported in this outcome. Part I is a clinician's evaluation of mentation (mental activity or state of mind), cognition (ability to acquire knowledge), behaviour and mood. Part II is the participants' evaluation of the disease's impact on normal activities. Part III is a clinician's evaluation of motor function. Parts I, II, and III contain a total of 31 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-124. Negative change from baseline values indicate improvement. All site raters (medical doctor [MD], doctor of osteopathy [DO], nurse practitioner, or physician assistant) received training on how to complete the UPDRS. The same site rater completed the UPDRS at all visits. | Day 0 (baseline), Week 18 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part II - Activities of Daily Living | The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. UPDRS contains four parts, the second of which is reported in this outcome. Part II is the participants' evaluation of the disease's impact on normal activities. Part II contains a total of 13 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-52. Negative change from baseline values indicate improvement. | Day 0 (baseline), Week 18 | 
| Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part III - Motor Function | The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. Version 3 of UPDRS contains four parts, the third of which is reported in this outcome. Part III is a clinician's evaluation of motor function. Part III contains 14 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-56. Negative change from baseline values indicate improvement. All site raters (medical doctor [MD], doctor of osteopathy [DO], nurse practitioner, or physician assistant) received training on how to complete the UPDRS. The same site rater completed the UPDRS at all visits | Day 0 (baseline), Week 18 | 
| Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater | CGI is used by the site rater to rate participants total improvement during the study whether or not, in the investigators' judgment, it is due entirely to drug treatment. Specifically, site raters are asked to compare the participants condition at the beginning of the study to his/her condition at Week 18, how much has he/she changed? Answers are 0 (not assessed), 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), 7(very much worse). Site raters can be the medical doctor [MD], doctor of osteopathy [DO], nurse practitioner, or physician assistant. | 18 weeks | 
| Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant | CGI is used by the participant to rate his/her total improvement during the study. Specifically, participants are asked to compare their condition at the beginning of the study to his/her condition at Week 18, how much has he/she changed? Answers are 0 (not assessed), 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), 7(very much worse). | 18 weeks | 
| Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater | Site raters were asked: Considering your total clinical experience with the particular population, how ill is the patient at this time? Answers were based on a 0-7 scale, with 0=not assessed, 1= normal, not at all ill, and 7= among the most extremely ill of patients. Site raters can be the medical doctor [MD], doctor of osteopathy [DO], nurse practitioner, or physician assistant. | Day 0 (baseline), Week 18 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's Disease, UPDRS, Clinical Global Evaluation Illness Severity score, Clinical Global Evaluation Improvement, B-SIT, SCOPA - Sleep Daytime Sleepiness, PDQ -39, SCOPA - Cognition, Levodopa, rasagiline, Dopamine Agonist Therapy, monoamine oxidase type B inhibitor