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

Study Overview
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Brief Summary
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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.

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

Conditions
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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 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.

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: SPM 962<br>SPM 962 transdermal patch | Drug: SPM 962<br>* SPM 962 transdermal patch once a daily up to 36.0 mg/day<br>|
| Placebo Comparator: Placebo<br>Placebo transdermal patch | Drug: Placebo<br>* Placebo transdermal patch<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 Sum Score | Mean change (LOCF) from baseline in UPDRS Part 3 sum score at 12 weeks after dosing. 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 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, 12 weeks after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UPDRS Part 2 Sum Score (Average Score of on State and Off State) | Mean change (LOCF) from baseline in UPDRS Part 2 sum score (average scores of on state and off state) at 12 weeks after dosing. Mean change (LOCF) from baseline in UPDRS Part 2 sum score (average score of on state and off state) at 12 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, 12 weeks after dosing | 
| Off Time | Mean change (LOCF) from baseline in off time at 12 weeks after dosing. | baseline, 12 weeks after dosing | 
| Effective Rate in UPDRS Part 3 Sum Score | Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in UPDRS Part 3 sum score at 12 weeks after dosing. | Baseline, 12 weeks after dosing | 
| UPDRS Part 1 Sum Score | Mean change (LOCF) from baseline in UPDRS Part 1 sum score at 12 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, 12 weeks after dosing | 
| Effective Rate in Off Time | Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in off time at 12 weeks after dosing. | Baseline, 12 weeks after dosing. | 
| UPDRS Part 2 Sum Score (on State) | Mean change (LOCF) from baseline in UPDRS Part 2 sum score (on state) at 12 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, 12 weeks after dosing | 
| UPDRS Part 2 Sum Score (Off State) | Mean change (LOCF) from baseline in UPDRS Part 2 sum score (off state) at 12 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, 12 weeks after dosing | 
| UPDRS Part 4 Sum Score | Mean change (LOCF) from baseline in UPDRS Part 4 sum score at 12 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, 12 weeks after dosing | 
| Total of UPDRS Part 2 Sum Score (Average Score of on State and Off State) and UPDRS Part 3 Sum Score | Mean change (LOCF) from baseline in total of UPDRS Part 2 sum score (average score of on state and off state), and UPDRS Part 3 sum score at 12 weeks after dosing. UPDRS sub-scale 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, 12 weeks after dosing | 
| Total of UPDRS Part 1 Sum Score, UPDRS Part 2 Sum Score (Average Score of on State and Off State), UPDRS Part 3 Sum Score, and UPDRS Part 4 Sum Score. | Mean change (LOCF) from baseline in total of UPDRS Part 1 sum score, UPDRS Part 2 sum score (average score of on state and off state), UPDRS Part 3 sum score, and UPDRS Part 4 sum score at 12 weeks after dosing. 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, 12 weeks after dosing | 
| The Modified Hoehn & Yahr Severity of Illness | Mean change (LOCF) from baseline in the Modified Hoehn & Yahr Severity of Illness at 12 weeks after dosing. The Modified Hoehn & 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, 12 weeks after dosing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, SPM 962, rotigotine, concomitant use of L-dopa