A Randomized, Double-blind, Active (Pramipexole 0.5 mg Tid) and Placebo Controlled, Study of Pramipexole Given 0.5 mg and 0.75 mg Bid Over 12-week Treatment in Early Parkinson's Disease (PD) Patients

Study Overview
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Brief Summary
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Primary objective: to assess the efficacy of pramipexole given two times daily compared to placebo. Secondary objectives: to assess the effects of pramipexole on mood, cognition, fatigue, impulse control, daytime sleepiness and nighttime sleep compared to placebo; to compare the tolerability among the treatment groups over 12 weeks

Official Title
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A Randomized, Double-blind, Active (Pramipexole 0.5 mg Tid) and Placebo Controlled, Efficacy Study of Pramipexole Given 0.5 mg and 0.75 mg Bid Over a 12-week Treatment Phase in Early Parkinson's Disease Patients (PramiBID)

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Pramipexole
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Potential subjects must meet all of the following inclusion criteria to be eligible for enrollment into this study: Must be willing and able to give informed consent. Must be over 30 years of age at Baseline. Must have idiopathic Parkinson's disease of less than 7 years duration since diagnosis, characterized by 2 of the following 3 cardinal signs (signs need to be asymmetric): resting tremor, bradykinesia and rigidity. Must have a Modified Hoehn and Yahr stage <3. Should be able to safely tolerate placebo for up to 12 weeks after Baseline. Must have a negative urine pregnancy test at the Screening Visit and use an adequate contraceptive method throughout the study if a woman of child-bearing potential. Women who are surgically sterile (hysterectomy or tubal ligation) or whose last menstruation was 12 months or more prior to the Screening Visit are considered to be of non-child-bearing potential. Acceptable forms of contraception include oral, implanted, or injected contraceptives intrauterine devices in place for at least 3 months estrogen patch and adequate barrier methods in conjunction with spermicide. Abstinence is considered an acceptable contraceptive regimen. Must be willing and able to comply with trial procedures. They must be sufficiently proficient in English to understand and complete study instruments. Exclusion Criteria: Individuals with any of the following characteristics will not be eligible for entry into this study: Signs or symptoms suggesting other parkinsonian syndromes. Use of medications that may cause secondary parkinsonism, including but not limited to: neuroleptics, metaclopramide, alphamethyldopa, flunarizine, methylphenidate, cinnarizine, reserpine, or amphetamines in the last 6 months prior to Baseline Visit. Use of dopaminergic medications within the last 3 months or for longer than 6 months prior to Baseline Visit. Presence of dementia by Diagnostic and Statistical Manual of Mental Disorders IV criteria (R06-1340) or a Mini Mental State Examination (R96-2656) (Appendix 10.1) score less than 26 at Screening Visit. Presence of major depression, as determined by medical history. Active epilepsy (i.e., occurrence of a seizure) within the past year prior to Baseline Visit. Electro Convulsive Therapy in previous 90 days prior to Baseline Visit. Myocardial infarction within previous 6 months prior to Baseline Visit. Third degree atrioventricular block or sick sinus syndrome. Congestive heart failure Class III or IV by New York Heart Association classification. Symptomatic orthostatic hypotension at Screening Visit. Stereotaxic brain surgery. Clinically significant liver disease. Clinically significant renal disease. Any other clinically significant medical or psychiatric condition (e.g., angina, active neoplasm) that in the judgment of the investigator would interfere with the subjects ability to participate in the study or would jeopardize safe conduct of the study. Breastfeeding. Known hypersensitivity or intolerability to pramipexole. Participating in other drug studies or receiving other experimental medications within 30 days of Baseline Visit. History of drug or alcohol dependency within 6 months of baseline visit.

Ages Eligible for Study
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Minimum Age: 31 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 |
| --- | --- |
| Other: Placebo<br> | Drug: Placebo<br> <br> |
| Other: Pramipexole 0.5 mg Tid<br>Pramipexole 0.5 mg tid (three times a day) | Drug: Pramipexole<br> <br> |
| Other: Pramipexole 0.5 mg Bid<br>Pramipexole 0.5 mg bid (bis in die (two times a day)) | Drug: Pramipexole<br> <br> |
| Other: Pramipexole 0.75 mg Bid<br>Pramipexole 0.75 mg bid (bis in die (two times a day)) | Drug: Pramipexole<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Unified Parkinson's Disease Rating Scale (UPDRS) Total Score | Total score ranges from zero (best) to 176 (worst), as the sum of Parts I (Mental questions), II (Activity of Daily Living questions), and III (Motor examination) | From baseline to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified Hoehn and Yahr Stage | Score ranges from best 0 (no signs of disease) to worst 5 (wheelchair bound or bedridden unless aided) | From baseline to week 12 | 
| Epworth Sleepiness Scale | Total score ranges from zero (best) to 24 (worst); scale has 8 items, each rated from zero (no chance of dozing) to 3 (high chance of dozing) | From baseline to week 12 | 
| Beck Depression Inventory II | Total score ranges from zero (best) to 63 (worst); scale has 21 items, each rated from zero (absent) to 3 (severe) | From baseline to week 12 |