A Dose-finding Study for SPM 962 in Advanced Parkinson's Disease Patients

A Placebo-controlled Dose-finding Study for SPM 962 in Advanced Parkinson's Disease Patients With Concomitant Treatment of L-dopa

The primary objective of this study is to investigate efficacy and safety of SPM 962 in advanced Parkinson's Disease (PD) patients in a multi-center, placebo-controlled study following once-daily multiple transdermal doses of SPM 962 within a range of 4.5 to 36.0 mg (12 weeks of dose titration/maintenance period). Recommended maintenance dose range is also to be investigated with distribution of the maintenance dose and accumulated response rate of efficacy.

Inclusion Criteria:

• Subject diagnosed as having Parkinson's disease in accordance with "Diagnostic Criteria established by the Research Committee of MHLW-specified Intractable Neurodegenerative Diseases (1995)".
• Subject is 30 and more and less than 80 years of age at the time of informed consent.
• Hoehn & Yahr stage 2-4 (on time).
• Total UPDRS Part 3 score is over 10 at screening test (on time).
• Subject is on a stable dose of L-dopa with no change in daily dose or dosing regimen for at least 28 days prior to the initial treatment of SPM 962.
• Subject has any of the following problematic symptoms; 1) Wearing off phenomenon 2) On and off phenomenon 3) Delayed-on and/or No-on phenomenon 4) Not well controlled with L-dopa due to adverse effect 5) Weakening of L-dopa efficacy.

Exclusion Criteria:

• Subject has previously participated in a trial with SPM 962.
• Subject is on other dopamine agonist treatment within 28 days prior to the initial treatment.
• Subject has psychiatric symptoms, e.g. confusion, hallucination, delusion, excitation, delirium, abnormal behavior at screening test or baseline.
• Subject has orthostatic hypotension.
• Subject has a history of epilepsy, convulsion and other.
• Subject has a complication of serious cardiac disorder or has the history.
• Subject has arrhythmia and treated with class 1a antiarrhythmic drugs (e.g. quinidine, procainamide etc.) or class 3 antiarrhythmic drugs (e.g. amiodarone, sotalol etc.).
• At screening and baseline, subject develops serious ECG abnormality. Subjects has QTc-interval >450 msec twice at screening. Subject has a the average QTc-interval from two ECGs >450 msec in males and >470 msec in females at baseline.
• Subject has congenital long QT syndrome.
• Subject has hypokalaemia.
• Subject has a total bilirubin >= 3.0 mg/dL or AST(GOT) or ALT(GPT) greater than 2.5 times of the upper limit of the reference range (or >= 100 IU/L) at screening test.
• Subject has BUN >= 25 mg/dL or serum creatinine >= 2.0 mg/dl at screening test.
• Subject has a history of allergic reaction to topical agents such as transdermal patch.
• Subject is pregnant or nursing or woman who plans pregnancy during the trial.
• Subject is receiving therapy with prohibited drug specified in the study protocol.
• Subject has a history of pallidotomy, thalamotomy, deep brain stimulation or fetal tissue transplant.
• Subject has dementia.
• Subject is unable to give consent.
• Subject is participating in another trial of an investigational drug or done so within 24 weeks prior to the initial treatment.
• Investigator judges that subject is inappropriate as a study subject with other reasons.