Long-term Safety Study of Open-label Pramipexole Extended Release (ER) in Patients With Early Parkinson´s Disease (PD).

Study Overview
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Brief Summary
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The general aim of this study is to obtain long-term safety and tolerability data on pramipexole ER, in daily doses from 0.375mg to 4.5mg once daily (q.d), in patients who have previously completed a pramipexole double-blind study in early PD (248.524(NCT00479401) or 248.636(NCT00558025) trial).

Official Title
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Long-term Safety Study of Open-label Pramipexole Extended Release (ER) in Patients With Early Parkinson´s Disease (PD).

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Placebo
* Drug: Pramipexole


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Completion of the double-blind trial 248.524 or 248.636 Male or female patient with early idiopathic Parkinson´s disease (PD), and with a Modified Hoehn and Yahr stage of I to III. Patient willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures. Signed informed consent obtained before any study procedures are carried out (in accordance with International Conference on Harmonisation (ICH) - Good Clinical Practice (GCP) guidelines and local legislation). Exclusion criteria: Patients prematurely withdrawn from the double-blind trials 248.524 or 248.636. Atypical parkinsonian syndromes due to drugs,metabolic disorders, encephalitis or degenerative diseases. Any psychiatric disorder according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria that could prevent compliance or completion of the study and/or put the patient at risk if he/she takes part in the study.4.History of psychosis, except history of drug induced hallucinations. 5. Clinically significant electrocardiogram (ECG) abnormalities at baseline. 6.Clinically significant hypotension 7.Malignant melanoma or history of previously treated malignant melanoma. 8.Any other clinically significant disease, that could put the patient at risk or could prevent compliance or completion of the study. 9. Pregnancy or breast-feeding. 10. Sexually active female of childbearing potential not using a medically approved method of birth control for at least one month prior to the baseline and throughout the study.11 Serum levels of aspartate aminotransferase (AST) (SGOT), alanine aminotransferase (ALT) (SGPT), alkaline phosphatase or bilirubin > 2 upper limit of normal (ULN) at baseline 12. Patients with a creatinine clearance < 50 mL/min (estimated by the Cockcroft and Gault formula). 13. Motor complications under levodopa therapy (e.g. on-off phenomena, dyskinesia) at baseline. 14. Any medication (including intra-muscular formulations) with central dopaminergic antagonist activity within 4 weeks prior to the baseline visit. 15.Any of the following drugs within 4 weeks prior to baseline: methylphenidate, cinnarizine, amphetamines. 16. Flunarizine within 3 months prior to baseline. 17. Known hypersensitivity to pramipexole or its excipients. 18. Drug abuse (including alcohol), according to investigator´s judgement, within 2 years prior to baseline. 19. Participation in investigational drug studies other than trials 248.524 and 248.636 or use of other investigational drug within one month or five times the half-life of the investigational drug prior to baseline.

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pramipexole<br>Patient to receive Pramipexole ER 0.375-4.5 mg tabl form daily | Drug: Pramipexole<br>* ER 0.375-4,5 mg<br>|
| Placebo Comparator: Placebo<br>Patient to receive placebo tablets identical to Pramipexole ER tablets. Only during transfer phase. | Drug: Placebo<br>* Patient to receive placebo tablets identical to Pramipexole ER tablets. Only during transfer phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Adverse Events, Adverse Drug Reactions, Serious Adverse Events | The aim of this study was to obtain long-term safety and tolerability data on pramipexole ER, in patients who have previously completed a pramipexole double blind study in early PD (248.524 (NCT00479401) or 248.636 (NCT00558025)). Therefore these items were considered as a safety evaluation | 80 weeks (patients from 248.524) or 72 weeks (patients from 248.636) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Unified Parkinson's Disease Rating Scale (UPDRS) II+III Total Score: Change From Baseline | UPDRS II+III ranging from 0 (normal) to 160 (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms | Open Label (OL) baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636) | 
| Number of Patients With UPDRS II+III Response From OL Baseline at Week 80 (Patients From 248.524) or Week 72 (Patients From 248.636) | A response means an improvement of >=20% from OL baseline. UPDRS II+III ranging from 0 (normal) to 160 (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms | OL Baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636) | 
| UPDRS I Total Score: Change From OL Baseline | UPDRS I ranging from 0 (normal) to 16 (severe), measures Mentation, Behavior and Mood | OL baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636) | 
| UPDRS II Total Score: Change From OL Baseline | UPDRS II ranging from 0 (normal) to 52 (severe), measures activity of daily living. | OL baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636) | 
| UPDRS III Total Score: Change From OL Baseline | UPDRS III ranging from 0 (normal) to 108 (severe) measures motor symptoms | OL baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636) | 
| Response in Clinical Global Impression of Improvement (CGI-I) | Clinicians evaluation in a rating scale of 7 steps, 1 meaning very much improved to 7 meaning very much worse. For patients previously treated with Placebo, all patients with at least much improved were considered as responders. For patients previously treated with Pramipexole ER or Immediate Release (IR), all patients with no change to very much improved were considered as responders | OL Baseline and week 32 (patients from 248.524) or week 24 (patients from 248.636) | 
| Response in Patient Global Impression of Improvement (PGI-I) | Patient rated evaluation of the PD symptoms on a rating scale of 7 steps, 1 meaning very much better to 7 meaning very much worse. For patients previously treated with Placebo, all patients with at least much better were considered as responders. For patients previously treated with pramipexole (PPX) ER or IR, all patients with no change to very much better were considered as responders | OL Baseline and week 32 (patients from 248.524) or week 24 (patients from 248.636) | 
| Parkinson Fatigue Scale (PFS-16) : Change From OL Baseline | PFS-16 ranging from 16 (better perceived health status) to 80 (severe symptoms of the disease) measuring aspects of fatigue that are relevant to patients with PD. | OL baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636) | 
| Number of Patients Introducing L-Dopa Medication in OL Trial | Number of patients requiring Levodopa supplementation during the study | 80 weeks (patients from 248.524) or 72 weeks (patients from 248.636) | 
| L-Dopa Dose: Change From OL Baseline | Change from open-label baseline in Levodopa dose | OL baseline and week 80 (patients from 248.524) or week 72 (patients from 248.636) | 
| Pramipexole Doses Respectively After 80 Weeks Compared to Pramipexole Doses at Week 8 for Previously 248.524 Patients and After 72 Weeks Compared to Pramipexole Doses at Week 0 for Previously 248.636 Patients | Change from open-label baseline in Levodopa dose over the final 72 weeks of open-label assessment | Week 8 and week 80 (patients from 248.524) or week 0 and week 72 (patients from 248.636) | 
| Patient Preference Regarding Treatment Dosing | Patients were surveyed on their preference for Once Daily dosing versus Three Times Daily dosing | 80 weeks (patients from 248.524) or 72 weeks (patients from 248.636) | 
| Patient Rating of Convenience of Treatment Dosing | Patients were surveyed on the convenience of Once Daily dosing versus Three Times Daily dosing | 80 weeks (patients from 248.524) or 72 weeks (patients from 248.636) |