Ophthalmologic Safety Study of Pramipexole Immediate Release (IR) Versus Ropinirole in Early Parkinson's Disease (PD) Patients

Study Overview
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Brief Summary
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To determine if there is any difference in the presence of retinal deterioration in PD patients treated with pramipexole IR versus ropinirole as monitored by comprehensive ophthalmologic assessments from baseline to the end of study at two years.

Official Title
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A Two Year Open Label, Randomized, Parallel Group, Blinded Assessment Ophthalmologic Safety Study of Pramipexole IR Versus Ropinirole in Early Parkinson's Disease Patients

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Mirapex
* Drug: Requip


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Diagnosis and main criteria for inclusion. Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study: Patients with idiopathic Parkinson's disease of less than 7 years characterized as Stage I-III by the Modified Hoehn and Yahr Scale and with a maximum of 6 months cumulative lifetime exposure to levodopa and/or dopamine agonist. Patients on current dopamine agonist therapy would require 14-day washout. Age at least 30 years. Women of childbearing potential must have a negative serum beta-HCG pregnancy test at the Screen (Baseline) visit and the patient must use adequate contraceptive methods. Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study. Patients who are willing and able to comply with scheduled visits, treatment plan, and other study procedures. Exclusion criteria Main criteria for exclusion. The presence of any of the following would make a patient ineligible for enrollment into the study: Previous history of allergic response or complications with any dopaminergic agonist drug Atypical PD syndromes History of stereotactic brain surgery Positive hepatitis B (surface antigen) or hepatitis C (antibody) Surgery within 180 days of randomization which would negatively impact participation Folstein's Mini Mental State Examination (MMSE) score of 24 or less History of active epilepsy (seizure) in the past 1 year Third degree AV block or sick sinus syndrome Congestive heart failure, Class III or IV Unstable heart disease such as unstable angina, dysrhythmia, or myocardial infarction in prior 6 months Symptomatic orthostatic hypotension Clinically significant liver disease or renal disease Malignant melanoma or history of previously treated malignant melanoma. Prohibited medications taken (including any drug known to have potential retino-toxic effects taken in the prior 12 months; neuroleptics taken within prior 6 months, MAO inhibitors except rasagiline or selegiline taken within prior 3 months, beta-blockers taken to treat Parkinson's disease in the prior 30 days, and Coenzyme Q10 taken within 14 days) Albinism/Albinoidism of any degree, type or syndrome History of glaucoma with or without treatment Inherited or acquired retinopathy such as age-related macular degeneration with visual loss Sarcoidosis Diabetes mellitus of any degree even if diet or insulin controlled Best corrected visual acuity (BCVA) of less than 20/40 by ETDRS Refractive error of greater than minus-6 diopters Abnormal electroretinogram (ERG) Unable to dilate pupils History of severe eye trauma that might affect the outcome of the study History of psychosis Participation in other investigational drug studies or use of investigational drugs within prior 30 days

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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Mirapex<br>Mirapex tablets three times daily (TID) dosing according to manufacturer's guidelines | Drug: Mirapex<br>* Standard marketed product dispensed according to manufacturer's guidelines<br>|
| Active Comparator: Requip<br>Requip tablets three times daily (TID) dosing according to manufacturer's guidelines | Drug: Requip<br>* Standard marketed product dispensed according to manufacturer's guidelines<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expert Panel Overall Assessment Following 2 Years on Drug | Expert panel of ophthalmologists assessed retinal deterioration by a review of the components of the comprehensive ophthalmology assessments | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expert Panel Overall Assessment Following 1 Year on Drug | Expert panel of ophthalmologists assessed retinal deterioration by a review of the components of the comprehensive ophthalmology assessments | up to 1 years | 
| Hoehn and Yahr Scale at Baseline | This scale is an investigator-completed assessment of the degree of complications arising from Parkinson's disease. The scale ranges from 0 (No signs) to 5 (Bedridden) | Baseline | 
| Hoehn and Yahr Scale at 1 Year | This scale is an investigator-completed assessment of the degree of complications arising from Parkinson's disease. The scale ranges from 0 (No signs) to 5 (Bedridden) | Up to 1 year | 
| Hoehn and Yahr Scale at 2 Years | This scale is an investigator-completed assessment of the degree of complications arising from Parkinson's disease. The scale ranges from 0 (No signs) to 5 (Bedridden) | Up to 2 years | 
| Unified Parkinson's Disease Rating Scale (UPDRS), Part II, Total Score at Baseline | Part II of the UPDRS collected retrospective information on patient functioning in various activities of daily living. Individual items scored from 0 (Normal) to 4 (Extreme dysfunction). The total score ranged from 0 to 52. | Baseline | 
| Unified Parkinson's Disease Rating Scale (UPDRS), Part II, Total Score at 1 Year | Part II of the UPDRS collected retrospective information on patient functioning in various activities of daily living. Individual items scored from 0 (Normal) to 4 (Extreme dysfunction). The total score ranged from 0 to 52. | 1 year | 
| Unified Parkinson's Disease Rating Scale (UPDRS), Part II, Change From Baseline in Total Score at 1 Year | Part II of the UPDRS collected retrospective information on patient functioning in various activities of daily living. Individual items scored from 0 (Normal) to 4 (Extreme dysfunction). The total score ranged from 0 to 52. | Baseline, 1 year | 
| Unified Parkinson's Disease Rating Scale (UPDRS), Part II, Total Score at 2 Years | Part II of the UPDRS collected retrospective information on patient functioning in various activities of daily living. Individual items scored from 0 (Normal) to 4 (Extreme dysfunction). The total score ranged from 0 to 52. | 2 years | 
| Unified Parkinson's Disease Rating Scale (UPDRS), Part II, Change From Baseline in Total Score at 2 Years | Part II of the UPDRS collected retrospective information on patient functioning in various activities of daily living. Individual items scored from 0 (Normal) to 4 (Extreme dysfunction). The total score ranged from 0 to 52. | Baseline, 2 year | 
| Unified Parkinson's Disease Rating Scale (UPDRS), Part III, Total Score at Baseline | Part III of the UPDRS contained the clinician-scored motor evaluation. Individual items scored from 0 (Normal) to 4 (Extreme dysfunction). The total score ranged from 0 to 56. | Baseline | 
| Unified Parkinson's Disease Rating Scale (UPDRS), Part III, Total Score at 1 Year | Part III of the UPDRS contained the clinician-scored motor evaluation. Individual items scored from 0 (Normal) to 4 (Extreme dysfunction). The total score ranged from 0 to 56. | 1 year | 
| Unified Parkinson's Disease Rating Scale (UPDRS), Part III, Change From Baseline in Total Score at 1 Year | Part III of the UPDRS contained the clinician-scored motor evaluation. Individual items scored from 0 (Normal) to 4 (Extreme dysfunction). The total score ranged from 0 to 56. | Baseline, 1 year | 
| Unified Parkinson's Disease Rating Scale (UPDRS), Part III, Total Score at 2 Years | Part III of the UPDRS contained the clinician-scored motor evaluation. Individual items scored from 0 (Normal) to 4 (Extreme dysfunction). The total score ranged from 0 to 56. | 2 years | 
| Unified Parkinson's Disease Rating Scale (UPDRS), Part III, Change From Baseline in Total Score at 2 Years | Part III of the UPDRS contained the clinician-scored motor evaluation. Individual items scored from 0 (Normal) to 4 (Extreme dysfunction). The total score ranged from 0 to 56. | Baseline, 2 year | 
| Unified Parkinson's Disease Rating Scale (UPDRS), Parts II and III, Total Score at Baseline | This is the sum of Part II and Part III of the UPDRS. The total score ranged from 0 (Normal) to 108 (Extreme dysfunction). | Baseline | 
| Unified Parkinson's Disease Rating Scale (UPDRS), Parts II and III, Total Score at 1 Year | This is the sum of Part II and Part III of the UPDRS. The total score ranged from 0 (Normal) to 108 (Extreme dysfunction). | 1 year | 
| Unified Parkinson's Disease Rating Scale (UPDRS), Parts II and III, Change From Baseline in Total Score at 1 Year | This is the sum of Part II and Part III of the UPDRS. The total score ranged from 0 (Normal) to 108 (Extreme dysfunction). | Baseline, 1 year | 
| Unified Parkinson's Disease Rating Scale (UPDRS), Parts II and III, Total Score at 2 Years | This is the sum of Part II and Part III of the UPDRS. The total score ranged from 0 (Normal) to 108 (Extreme dysfunction). | 2 years | 
| Unified Parkinson's Disease Rating Scale (UPDRS), Parts II and III, Change From Baseline in Total Score at 2 Years | This is the sum of Part II and Part III of the UPDRS. The total score ranged from 0 (Normal) to 108 (Extreme dysfunction). | Baseline, 2 year | 
| Clinical Abnormal Findings: Clinical Laboratory Evaluations (Biochemistry and Haematology)and Vital Signs | Clinical relevant abnormalities for clinical laboratory evaluations Biochemistry and Haematology) and Vital Signs. New abnormal findings or worsening of baseline conditions were reported. | Screen (Baseline) and final visit (24 months) |