A Long-Term Extension Trial From Late Phase II of SPM 962 in Patients With Restless Legs Syndrome

Study Overview
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Brief Summary
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The aims of the trial are to assess the safety and the efficacy of SPM 962 following once-a-daily transdermal administration within a range of 2.25 to 6.75 mg/day in Japanese patients with restless legs syndrome (RLS) in a multi-center, open-label trial. The maximum treatment period is 53 weeks. The trial is an extension trial from the precedent 6-week, double-blind, randomized, placebo-controlled, parallel-group comparative trial(243-07-003). The trial is also for an exploratory investigation of incidence of augmentation, the most problematic complications in dopaminergic treatment.

Official Title
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An Open-label Long-term Extension Trial From Late Phase II of SPM 962 (243-07-003) in Patients With Restless Legs Syndrome

Conditions
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Idiopathic Restless Legs Syndrome

Intervention / Treatment
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* Drug: SPM 962


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject completed the preceding trial 243-07-003 (NCT00666965) Exclusion Criteria: Subject discontinued from the preceding trial 243-07-003 (NCT00666965) Subject had a serious adverse event which association with the investigational drug is not ruled out during trial 243-07-003 Subject had a persistent serious adverse event at the baseline, which was observed and association with the investigational drug is ruled out during trial 243-07-003. Subject had persistent hallucination or delusion during trial 243-07-003. Subject had psychiatric conditions such as confusion, excitation, delirium, abnormal behaviour at the baseline. Subject had orthostatic hypotension or a systolic blood pressure (SBP) ≤ 100 mmHg and had a decrease of SBP from spine to standing position ≥ 30 mmHg at baseline. Subject had a history of epilepsy, convulsion etc. during trial 243-07-003. Subject developed serious ECG abnormality at the baseline. Subject had QTc-interval ≥ 500 msec at the baseline or subject had an increase of QTc-interval ≥ 60 msec from the baseline in the trial 243-07-003 and had 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 243-07-003. Subject had 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 243-07-003. Subject had BUN ≥ 30 mg/dL or serum creatinine ≥ 2.0 mg/dl at the end of the taper period in trial 243-07-003. Subject who planned pregnancy during the trial. Subject was judged to be inappropriate for this trial by the investigator for the reasons other than above.

Ages Eligible for Study
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Minimum Age: 20 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>Rotigotine transdermal patch | Drug: SPM 962<br>* Tansdermal patch<br>* Other names: rotigotine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The 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 adverse events, 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 | Up to 54 weeks | 
| Augmentation | Augmentation is the main complication during long-term dopaminergic treatment of restless legs syndrome (RLS) and reflects an overall increase in RLS severity. Augmentation is clinically significant when at least one of the following occurs: Change in daily activities and/or behavior (e.g., the patient stops riding in cars in the afternoon) due to augmentation; Negative impact on the patient's quality of life (sleep, mood, etc.) due to augmentation; Need to change the treatment dose or the patienｔ needs to take the dose earlier in the day (e.g., dividing the dose); Adjustments in concomitant medication are made to compensate for augmented RLS symptoms (e.g., an increased intake of analgesics or hypnotics to cover an increase in symptom intensity); Any other aspect as judged by the evaluator (should be specified). | Up to 53 weeks | 
| Change of the Pittsburgh Sleep Quality Index (PSQI) From Baseline to Each Visit | PSQI is a scale for assessing severity of sleep disorders. The score ranges from 0 to 21. 0 indicates no difficulty and 21 indicates severe difficulty. A decrease in the scores means improvement. | Baseline, Up to 53 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of IRLS Sum Score From the Baseline to Each Visit | IRLS is a scale for assessing severity of restless legs syndrome symptoms. IRLS consists of ten questions. Each question is scored from 4 for the first (top) answer (usually 'very severe') to 0 for the last answer (usually none). The sum of the score of each question serves as the scale score. The scale scoring criteria are: Mild (score 1-10); Moderate (score 11-20); Severe (score 21-30); Very severe (score 31-40). A decrease in the scores means improvement. | Baseline, Up to 53 weeks | 
| Efficacy Rate in IRLS Sum Score | Efficacy rate (percentage of subjects with 50% decrease) (LOCF) in IRLS sum score. | Baseline, Up to 53 weeks | 
| Change of Augmentation Severity Rating Scale (ASRS) Sum Score From Baseline to Each Visit | ASRS is a scale for assessing severity of augmentation. ASRS consists of 3 items (one item containing 4 sub-items). The sum of the score of each question serves as the scale score (each question score: 0-3, sum score 0-24). A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement. | Baseline, Up to 52 weeks | 
| Change of Short-Form 36-Item Health Survey (SF-36) From Baseline to Each Visit | SF-36 is a scale for assessing health status in clinical practice and research. The scores of 36 questions are summarized into 7 sub-scales. In each sub-scale which range is 0-100, a higher score indicates a better health status. Thus a increase in the scores means improvement. | Baseline, Up to 53 weeks |