Efficacy, Safety, Tolerability of Pramipexol ER Versus Pramipexol IR Versus Placebo in Early PD Patients
Condition: Early Parkinson Disease (Early PD)
MeSH terms: Parkinson Disease
Intervention: Pramipexol Extended Release; Pramipexol Immediate Release; Placebo
Intervention MeSH terms: Pramipexole
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 539.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No

Summary:

      The objectives of this trial conducted in early Parkinson's Disease (PD) patients are to
      determine the efficacy (as measured by the change from baseline to the end of the maintenance
      phase in the total score for the Unified Parkinson's Disease Rating Scale (UPDRS) Parts II
      and III combined), safety, and tolerability of Pramipexole Extended Release (ER) (in daily
      doses from 0.375mg to 4.5mg q.d.) in comparison to placebo, and to test for non-inferiority
      between the two formulations (ER and IR) of pramipexole.

      In addition, the efficacy of Pramipexole Immediate Release (IR) will be compared to placebo,
      for assay sensitivity
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female patient with idiopathic Parkinsons disease (PD) confirmed by at least
             two of the following signs: resting tremor, bradykinesia, rigidity.

          2. Parkinsons disease diagnosed within 5 years.

          3. Patients 30 years of age or older at the time of diagnosis.

          4. Modified Hoehn and Yahr stage of 1 to 3.

          5. Patients requiring additional therapy/ introduction of therapy (for de novo patients)
             to treat their parkinsonian symptoms at the time of enrollment (screening visit, V1)
             according to the investigators judgement.

        Exclusion Criteria:

          1. Atypical parkinsonian syndromes due to drugs (e.g., metoclopramide, flunarizine),
             metabolic disorders (e.g., Wilson's disease), encephalitis or degenerative diseases
             (e.g., progressive supranuclear palsy).

          2. Dementia, as defined by a Mini-Mental State Exam score < 24 at screening visit

          3. Any psychiatric disorder according to Diagnostic and Statistical Manual of Mental
             Disorders 4th (DSM-IV)

          4. History of psychosis

          5. Clinically significant electrocardiogram (ECG) abnormalities at screening visit

          6. Clinically significant hypotension

          7. Malignant melanoma or history of previously treated malignant melanoma

          8. Any other clinically significant disease, whether treated or not, that could put the
             patient at risk or could prevent compliance or completion of the study

          9. Pregnancy

         10. Sexually active female of childbearing potential not using a medically approved method
             of birth control

         11. Serum levels of Aspartate Aminotransferase (AST) , Alanine Aminotransferase (ALT),
             alkaline phosphatases or bilirubin > 2 Upper Limit of Normal (ULN)

         12. Patients with a creatinine clearance < 50 mL/min

         13. Any dopamine agonist (including pramipexole) within 4 weeks prior to baseline visit,
             or L-Dopa within 8 weeks prior to baseline visit.

         14. Total cumulative duration of prior exposure to Levodopa of more than 3 months.

         15. Any medication (including intra-muscular formulations) with central dopaminergic
             antagonist activity within 4 weeks prior to the baseline visit

         16. Any of the following drugs within 4 weeks prior to the baseline visit:
             methylphenidate, cinnarizine, amphetamines.

         17. Flunarizine within 3 months prior to baseline visit

         18. Known hypersensitivity to Pramipexole or its excipients

         19. Drug abuse (including alcohol), according to Investigators judgement, within 2 years
             prior to screening.

         20. Participation in other investigational drug studies or use of other investigational
             drugs within one month or five times the half-life of the investigational drug