Pivotal Study in Advanced Parkinsons Disease Patients
Condition: Parkinson Disease
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
Intervention model: Parallel Assignment
Enrollment: 517.0
Sex: All
Minimum age: 32 Years
Healthy volunteers: No

Summary:

      The general aim of this trial is to determine the efficacy (as measured by the change from
      baseline to the end of the maintenance phase in the total score for Unified Parkinsons
      Disease Rating Scale Parts II and III combined), safety, and tolerability of pramipexole ER,
      in daily doses from 0.375 milligram to 4.5 milligram once a day, in comparison to placebo, in
      Levodopa combined with a Dopa-Decarboxylase-inhibitor treated Parkinson patients with
      advanced Parkinsons Disease and motor fluctuations.

      In addition, a numerical comparison of the efficacy of pramipexole extended release versus
      pramipexole immediate release will be done.

      The efficacy of pramipexole immediate release will also be compared to placebo, for assay
      sensitivity.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female patient with advanced idiopathic Parkinsons disease confirmed by at
             least two of the following signs: resting tremor, bradykinesia, rigidity.

          2. Parkinsons disease diagnosed for at least 2 years.

          3. Patients 30 years of age or older at the time of diagnosis.

          4. Modified Hoehn and Yahr stage of 2 to 4 at on-time.

          5. Treatment with standard or controlled release Levodopa combined with a
             Dopa-Decarboxylase-inhibitor, or with Levodopa combined with a
             Dopa-Decarboxylase-inhibitor/entacapone, at an optimised dose according to
             investigators judgement, this dose being stable for at least 4 weeks prior to baseline
             visit.

          6. Motor fluctuations, with at least 2 cumulative hours of off-time every day during
             waking hours (documented on a patient diary completed for 2 consecutive days before
             baseline visit).

          7. Patient willing and able to comply with scheduled visits, treatment plan, laboratory
             tests and other study procedures. In particular, after training, it has to be
             documented at baseline visit that the patient is able to recognise the off-time and
             on-time periods during waking hours and that the patient (or a family member or a
             guardian) is able to record them accurately in the patient diary.

          8. Signed informed consent obtained before any study procedures are carried out (in
             accordance with International Conference on Harmonisation-Good Clinical Practice
             guidelines and local legislation).

        Exclusion Criteria:

          1. Atypical parkinsonian syndromes due to drugs, metabolic disorders, encephalitis or
             degenerative diseases

          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 edition 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. History of deep brain stimulation

          6. Clinically significant Electrocardiogram abnormalities at screening visit

          7. Clinically significant hypotension and/or symptomatic orthostatic hypotension at
             screening or baseline visit

          8. Malignant melanoma or history of previously treated malignant melanoma

          9. 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

         10. Pregnancy or breast-feeding

         11. Sexually active female of childbearing potential not using a medically approved method
             of birth control for at least one month prior to the screening visit and throughout
             the study period

         12. Serum levels of Aspartate Aminotransferase (Serum Glutamic-Oxaloacetic Transaminase),
             Alanine Aminotransferase (Serum Glutamic Pyruvic Transaminase), alkaline phosphatases
             or bilirubin > 2 Upper Limit of Normal

         13. Patients with a creatinine clearance < 50 millilitres/minute

         14. Any dopamine agonist (including pramipexole) within 4 weeks prior to baseline visit

         15. Any medication with central dopaminergic antagonist activity within 4 weeks prior to
             the baseline visit

         16. Any of the following drugs within 4 weeks prior to 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 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
             (whichever is longer) prior to baseline visit