A 12-week Study of Pramipexole Extended Release (ER) in Patients With Parkinson's Disease (PD), Followed by a 52-week Long-term Treatment Period

A Double-blind, Double-dummy, Randomised, Parallel-group Study to Investigate the Safety, Tolerability, Trough Plasma Concentration, and Efficacy of Pramipexole ER Versus Pramipexole Immediate Release (IR) Administered Orally for 12 Weeks in Patients With Parkinson's Disease (PD) on L-dopa Therapy, Followed by a 52-week Open-label Long-term Treatment Period to Evaluate the Long-term Safety and Efficacy of Pramipexole ER

The objective of this trial is to investigate the safety, tolerability, trough plasma concentration, and efficacy of pramipexole ER in comparison with those of pramipexole IR administrated orally for 12 weeks in patients with PD on levodopa (L-DOPA) therapy (the double-blind period). The double-blind period will be followed by the open-label 52 week administration of pramipexole ER to evaluate the long term safety and efficacy (the open-label period).

Inclusion criteria

1. Male or female patients with diagnosis of PD including juvenile Parkinsonism, in whom the onset began at the age of forty or younger.

2. Patients with a modified Hoehn and Yahr scale of II to IV at "on" time.

3. Patients who have received an individual dosage of L-DOPA (either standard L-DOPA or L-DOPA with dopa-decarboxylase inhibitor) at a stable dose for at least 4 weeks before the baseline visit (Visit 2).

4. Patients who exhibit any therapeutically problematic issues or status based on L-DOPA therapy:

   • wearing-off phenomena
   • no on /delayed on
   • dystonia at off time
   • on-off phenomena
   • freezing phenomena at off time
   • the sub-optimal dose of L-DOPA had been administered due to side effects (such as dyskinesia), or therapeutical strategy

Exclusion criteria

1. Atypical parkinsonian syndromes due to drugs, metabolic disorders, encephalitis or degenerative diseases.
2. Dementia, as defined by a Mini-Mental State Examination (MMSE) score <24 at screening visit.
3. Any psychiatric disorder according to DSM-IV criteria that could prevent compliance or completion of the trial and/or put the patient at risk if he/she takes part in the trial.
4. History of psychosis, except history of drug induced hallucinations (provided the investigator considers that participation in the trial would not represent a significant risk for the patient).
5. Clinically significant ECG abnormalities at screening visit, according to investigator's judgement.
6. Clinically significant hypotension or symptomatic orthostatic hypotension (i.e., clinical symptoms of orthostatic hypotension such as dizziness postural etc associated with a decline >=20 mmHg in systolic blood pressure and a decline >=10 mmHg in diastolic blood pressure, at one minute after standing compared with the previous supine systolic and diastolic blood pressure obtained after 5 minutes of quiet rest) either at screening visit or at baseline visit.
7. Any other clinically significant disease, whether treated or not, that could put the patient at risk or could prevent compliance or completion of the trial.
8. Pregnancy (to be excluded by serum pregnancy test at screening visit) or breast-feeding.
9. Sexually active female of childbearing potential not using a medically approved method of birth control within one month before to the screening visit and throughout the trial period.
10. Serum levels of AST, ALT, alkaline phosphatases or bilirubin >2 upper limits of normal .
11. Patients with a creatinine clearance <50 mL/min
12. Patients with a complication or signs of malignant tumours or those within 5 years after the treatment.