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

Study Overview
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Brief Summary
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The primary objective of this trial is to establish the maximum maintenance dose of SPM 962 in patients with Parkinson's disease in a multi-center, uncontrolled, open-label study by conducting safety evaluation of each patient following once-daily transdermal doses of SPM 962 within a range of 4.5 to 36.0 mg. (The administration period will consist of a standard 8-week dose-titration period, 4-week dose-maintenance period, and a dose de-escalation period) Exploratory evaluation of each patient's maintenance dose will also be conducted with attention to patient safety. The relationship of pharmacokinetics, safety, and efficacy will also be examined.

Official Title
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A Open-label Dose-ranging Study for SPM 962 in Parkinson's Disease Patients

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: SPM 962


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For subject with early and advanced Parkinson's disease 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. Gender and inpatient-outpatient status are not specified. For subject with early Parkinson's disease Hoehn & Yahr stage 3 or less. Subject who has not taken L-dopa within 28 days prior to initial administration of SPM 962. For subject with dvanced Parkinson's disease Hoehn & Yahr stage 2-4. Subject is on a stable dose of L-dopa with no change in daily dose or dosing regimen for at least 7 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) Not well controlled with L-dopa due to adverse effect 4) Weakening of L-dopa efficacy. Exclusion Criteria: Subject is on other dopamine agonist treatment within 7 days prior to the initial treatment. Subject is on cabergoline treatment within 14 days prior to the initial treatment. Subject has psychiatric symptoms, e.g. confusion, hallucination, delusion, excitation, delirium, abnormal behavior. 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 at screening. Subject has QTc-interval >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). Subject has BUN >= 25 mg/dL or serum creatinine >= 2.0 mg/dl. 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 6 months 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


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>* Other names: rotigotine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maintenance Dose of the SPM962 | The maintenance dose of the SPM 962 was examined based on the safety and efficacy. | Up to 12 weeks after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Severity of Adverse Events, Vital Signs, and Laboratory Parameters | Incidence and severity of adverse events, vital signs, and laboratory parameters following the initiation of study treatment. | Up to 12 weeks after dosing | 
| Total of Unified Parkinson's Disease Rating Scale (UPDRS) Part 2 Sum Score and Part 3 Sum Score for Early Parkinson's Disease Without Concomitant L-dopa Therapy | Mean change (LOCF) from baseline in Total of UPDRS Part 2 sum score and Part 3 sum 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 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 | 
| UPDRS Part 3 Sum Score for Advanced Parkinson's Disease With Concomitant L-dopa Therapy | Mean change (LOCF) from baseline in UPDRS Part 3 sum score at 12 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, 12 weeks after dosing | 
| UPDRS Part 2 Sum Score for Early Parkinson's Disease Without Concomitant L-dopa Therapy | Mean change (LOCF) from baseline in UPDRS Part 2 sum score 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 3 Sum Score for Early Parkinson's Disease Without Concomitant L-dopa Therapy | Mean change (LOCF) from baseline in UPDRS Part 3 sum score at 12 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, 12 weeks after dosing | 
| UPDRS Part 2 Sum Score (on State) for Advanced Parkinson's Disease With Concomitant L-dopa Therapy. | 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) for Advanced Parkinson's Disease With Concomitant L-dopa Therapy. | 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 2 Sum Score (Average Score of on State and Off State) for Advanced Parkinson's Disease With Concomitant L-dopa Therapy | 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 | 
| Total of UPDRS Part 2 Sum Score (Average Score of on State and Off State) and Part 3 Sum Score for Advanced Parkinson's Disease With Concomitant L-dopa Therapy | Mean change (LOCF) from baseline in Total of UPDRS Part 2 sum score (average score of on state and off state) and 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 | 
| Off Time for Advanced Parkinson's Disease With Concomitant L-dopa Therapy | Mean change (LOCF) from baseline in off time at 12 weeks after dosing. | Baseline, 12 weeks after dosing | 

 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