A Placebo-controlled Study for SPM 962 in Early Parkinson's Disease Patients

Study Overview
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Brief Summary
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To investigate superiority of SPM 962 over placebo in early Parkinson's disease patients in a multi-center, placebo-controlled, double-blind study following once-daily multiple transdermal doses of SPM 962 within a range of 4.5 to 36.0 mg (12-week dose titration/maintenance period)

Official Title
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A Placebo-controlled Study for SPM 962 in Early Parkinson's Disease Patients With Non-concomitant Treatment of L-dopa

Conditions
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Early Parkinson's Disease

Intervention / Treatment
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* Drug: SPM 962
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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 years < > 80 years at the time of informed consent Hoehn & Yahr stage 1- 3 Total of each sum score of UPDRS Part 2 and 3 is over 10 at screening test Exclusion Criteria: Subject has previously participated in a trial with SPM 962 Subject is on L-dopa treatment for total of over 6 months at the time of informed consent Subject has psychiatric symptoms, e.g. confusion, hallucination, delusion, excitation, delirium, abnormal behavior at screening test and baseline Subject has orthostatic hypotension Subject has a history of epilepsy, convulsion and other Subject has a complication of serious cardiac disorder/arrhythmia or has the history Subject has arrhythmia and treated with class 1a anti-arrhythmic drugs (e.g. quinidine, procainamide etc.) or class 3 anti-arrhythmic drugs (e.g. amiodarone, sotalol etc.) Subject has serious ECG abnormal at screening i.e.; 1) Subject has more than 450 msec of QTc values both in two measurements at screening test 2) Subject has more than 470 msec for females and more than 450 msec for males of mean QTc values of two measurements at baseline Subject has congenital long QT syndrome Subject has serum potassium of less than 3.5 mEq/L at screening test. Subject has total bilirubin of 3.0 mg/dL and above or AST(GOT), ALT(GPT) greater than 2.5 times (or 100 IU/L and above) of the clinical laboratory's upper limit of the reference range at screening test Subject has 30 mg/dL and above of BUN or 2.0 mg/dL and above of serum creatinine at screening test Subject has a history of allergy to topical medicine, e.g. transdermal patch Subject is pregnant, nursing, or is child bearing potential while 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 12 weeks prior to the initial treatment Investigator judges that subject is inappropriate as a study subject with other reasons

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 79 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: SPM 962<br>* transdermal application, 1 time per day<br>|
| Placebo Comparator: 2<br> | Drug: placebo<br>* transdermal application, 1 time per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to the End of Maintenance Period in Total of Each Sum Score of UPDRS Part 2 and Part 3 | Mean change (LOCF) from baseline to the end of maintenance period in total of each sum score of UPDRS Part 2 and Part 3. UPDRS is a scale for monitoring Parkinson's Disease-related disability and impairment. The UPDRS consists of the following four sub-scales. Part 1: Mentation, Part 2: Activities of Daily Living, Part 3: Motor, Part 4: Complications. Part 2 assesses 13 items and Part 3 assesses 14 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement. | baseline, end of maintenance period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy Rate in Total of Each Sum Score of UPDRS Part 2 and Part 3 | Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in total of each sum score of UPDRS Part 2 and Part 3 at the end of maintenance period | baseline, end of maintenance period | 
| Mean Change in UPDRS Part 2 Sum Score | Mean change (LOCF) from baseline in UPDRS Part 2 sum score at every two weeks after dosing. UPDRS sub-scale Part 2 assesses 13 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement. | Baseline, every two weeks | 
| Efficacy Rate in UPDRS Part 2 Sum Score | Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in UPDRS Part 2 sum score at every two weeks after dosing. | Baseline, every two weeks | 
| UPDRS Part 3 Sum Score | Mean change (LOCF) from baseline in UPDRS Part 3 sum score at every two weeks after dosing. UPDRS sub-scale Part 3 assesses 14 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement. | Baseline, every two weeks | 
| Efficacy Rate in UPDRS Part 3 Sum Score | Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in UPDRS Part 2 sum score at every two weeks after dosing. | Baseline, every two weeks | 
| UPDRS Part 1 Sum Score | MMean change (LOCF) from baseline in UPDRS Part 1 sum score at every two weeks after dosing. UPDRS sub-scale Part 1 assesses 4 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement. | Baseline, every two weeks | 
| UPDRS Part 4 Sum Score | Mean change (LOCF) from baseline in UPDRS Part 4 sum score at every two weeks after dosing. UPDRS sub-scale Part 4 assesses 11 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement. | Baseline, every two weeks | 
| Total of Each Sum Score of UPDRS Part 1, 2, 3, and 4 | Mean change (LOCF) from baseline to the end of maintenance period in total of each sum score of UPDRS Part 1, 2, 3 and 4. UPDRS sub-scale Part 1, 2, 3, and 4 assess 4, 13, 14, and 11 items respectively. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement. | Baseline, every two weeks | 
| The Modified Hoehn and Yahr Stage | Mean change (LOCF) from baseline in the Modified Hoehn and Yahr Severity of Illness at the end of maintenance period. The Modified Hoehn and Yahr criteria are measured on the following 8-point scale for staging: 0, No signs of disease; 1, Unilateral disease; 1.5, Unilateral plus axial involvement; 2, Bilateral disease without impairment of balance; 2.5, Mild bilateral disease with recovery on pull test; 3, Mild to moderate bilateral disease, some postural instability, physically independent 4, Severe disability, still able to walk or stand unassisted; and 5, Wheelchair bound or bedridden unless aided. | Baseline, end of maintenance period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SPM 962, rotigotine, Parkinson's disease, monotherapy