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

• UPDRS Part 2 sum score [ Time Frame: baseline, 12 weeks after dosing ] [ Designated as safety issue: No ]
  Mean change (LOCF) from baseline in UPDRS Part 2 sum score (average scores of on state and off state) at 12 weeks after dosing.
• off time [ Time Frame: baseline, 12 weeks after dosing ] [ Designated as safety issue: No ]
  Mean change (LOCF) from baseline in off time at 12 weeks after dosing.

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.

• Drug: SPM 962
  SPM 962 transdermal patch once a daily up to 36.0 mg/day
• Drug: Placebo
  Placebo transdermal patch

• Experimental: SPM 962
  SPM 962 transdermal patch
  Intervention: Drug: SPM 962
• Placebo Comparator: Placebo
  Placebo transdermal patch
  Intervention: Drug: Placebo

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.