A Long-Term Extension Trial From of SPM 962 in Advanced Parkinson's Disease Patients

Study Overview
=================
Brief Summary
-----------------
To investigate the safety of once-daily repeated transdermal administration of SPM 962 within a dose range of 4.5 to 36.0 mg/day (54-week treatment period) in Parkinson's disease (PD) patients treated concomitantly with L-dopa in a multi-center, open-label uncontrolled study. To investigate efficacy of SPM 962 in an exploratory manner.

Official Title
-----------------
An Open-label Long-term Extension Trial From Phase III of SPM962 (243-08-002) in Advanced Parkinson's Disease Patients With Concomitant Treatment of L-dopa

Conditions
-----------------
Parkinson's Disease

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject completed the preceding trial 243-08-001. Exclusion Criteria: Subject discontinued from the preceding trial 243-08-001. Subject had a serious adverse event which association with the investigational drug was not ruled out during trial 243-08-001. Subject has a persistent serious adverse event at the baseline, which was observed and association with the investigational drug was ruled out during trial 243-08-001. Subject had persistent confusion, hallucination, delusion or excitation during trial 243-08-001. Subject has abnormal behavior such as obsessive-compulsive disorder and delusion in 243-08-001 study. Subject showed serious or extensive application site reactions beyond the application site in the 243-08-001 study. Subject has orthostatic hypotension or a systolic blood pressure (SBP) <= 100 mmHg and has a decrease of SBP from spine to standing position >= 30 mmHg at baseline. Subject has a history of epilepsy, convulsion etc. during trial 243-08-001. Subject develops serious ECG abnormality at the baseline. Subject has QTc-interval >= 500 msec at the baseline or subject has an increase of QTc-interval >= 60 msec from the baseline in the trial 243-08-001 and has a QTc-interval > 470 msec in female or > 450 msec in male at the baseline. Subject had a serum potassium level < 3.5 mEq/L at the end of the taper period in trial 243-08-001. 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 the end of the period in trial 243-08-001. Subject had BUN >= 30 mg/dL or serum creatinine >= 2.0 mg/dl at the end of the taper period in trial 243-08-001. Subject who plans pregnancy during the trial. Subject is unable to give consent. Subject is judged to be inappropriate for this trial by the investigator for the reasons other than above.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and Severity of Adverse Events (AEs), Vital Signs, and Laboratory Parameters | The safety of the long-term SPM 962 treatment was examined based on the incidence and severity of AEs, vital signs, and laboratory parameters. AEs of special interest (1-3) are defined as below: sudden onset of sleep obsessive-compulsive disorder or impulse-control disorder hallucination, delusion Application site reaction is scored as -, ±, +, ++, +++, or ++++. More + indicates a greater severity of symptoms. The worst score obtained throughout the evaluation period was to be assessed. | Up to 55 weeks after dosing | 

Secondary 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 (on state). 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, Up to 54 weeks after dosing | 
| UPDRS Part 2 Sum Score (Average of on State and Off State) | Mean change (LOCF) from baseline in UPDRS Part 2 sum score (average of on state and off state). 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, up to 54 weeks after dosing | 
| Absolute Time Spent Off | Mean number of hours in off state during a 24-hour period. | Baseline, up to 54 weeks after dosing | 
| UPDRS Part 1 Sum Score | Mean change (LOCF) from baseline in UPDRS Part 1 sum score. 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, up to 54 weeks after dosing | 
| UPDRS Part 2 Sum Score (On State) | Mean change (LOCF) from baseline in UPDRS Part 2 sum score (on state). A decrease in the scores means improvement. | Baseline, up to 54 weeks after dosing | 
| UPDRS Part 2 Sum Score (Off State) | Mean change (LOCF) from baseline in UPDRS Part 2 sum score (off state). A decrease in the scores means improvement. | Baseline, up to 54 weeks after dosing | 
| UPDRS Part 4 Sum Score | Mean change (LOCF) from baseline in UPDRS Part 4 sum score. 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, up to 54 weeks after dosing | 
| Total of UPDRS Part 1 Sum Score, UPDRS Part 2 Sum Score (Average of on State and Off State), UPDRS Part 3 Sum Score (on State), 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 of on state and off state), UPDRS Part 3 sum score (on state), and UPDRS Part 4 sum score. A decrease in the scores means improvement. | Baseline, up to 54 weeks after dosing | 
| The Modified Hoehn & Yahr Severity of Illness | Change (LOCF) from baseline in the Modified Hoehn & Yahr Severity of Illness. 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. The data at week 52 is shown. | Baseline, up to 54 weeks after dosing. | 
| Each Item of UPDRS Part 1 | The percentage of subjects with elevated scores for each item of UPDRS Part 1. The data at week 52 is shown. | Baseline, up to 54 weeks after dosing. | 
| Each Item of UPDRS Part 2 (on State) | The percentage of subjects with elevated scores for each item of UPDRS Part 2 (on state). The data at week 52 is shown. | Baseline, up to 54 weeks after dosing. | 
| Each Item of UPDRS Part 2 (Off State) | The percentage of subjects with elevated scores for each item of UPDRS Part 2 (off state). The data at week 52 is shown. | Baseline, up to 54 weeks after dosing. | 
| Each Item of UPDRS Part 2 (Average of on State and Off State) | The percentage of subjects with elevated scores for each item of UPDRS Part 2 (average of on state and off state). The data at week 52 is shown. | Baseline, up to 54 weeks after dosing. | 
| Total of UPDRS Part 2 Sum Score (Average of on State and Off State) and UPDRS Part 3 Sum Score (on State) | Mean change (LOCF) from baseline in total of UPDRS Part 2 sum score (average of on state and off state) and UPDRS Part 3 sum score (on state). A decrease in the scores means improvement. | Baseline, up to 54 weeks after dosing | 
| Each Item of UPDRS Part 3 (on State) | The percentage of subjects with elevated scores for each item of UPDRS Part 3 (on state). The data at week 52 is shown. | Baseline, up to 54 weeks after dosing. | 
| Each Item of UPDRS Part 4 | The percentage of subjects with elevated scores for each item of UPDRS Part 4. The data at week 52 is shown. | Baseline, up to 54 weeks after dosing. | 

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