A Placebo-Controlled Study for SPM 962 in Restless Legs Syndrome (RLS) 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 Japanese RLS patients in a multi-center, placebo-controlled double-blind parrallel group comparative study following once-daily multiple transdermal doses of SPM 962 within a range of 2.25 to 6.75 mg/day. Recommended maintainance dose range is also to be investigated.

Official Title
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A Placebo-Controlled Study for SPM 962 in RLS Patients

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 is 20 and more and less than 80 years of age and is able to think about her/his participation at the time of informed consent. Subject meets the diagnosis of idiopathic RLS based on the 4 cardinal clinical features according to the IRLSSG/NIH. The following subject will be included in the study Subject is not currently receiving treatment for RLS. Subject has previously received treatment of either L-dopa or dopamine agonists and efficacy was observed in either of drugs. At baseline, subject has a score of ≧ 15 on the IRLS sum score and RLS symptoms occur twice and more a week (≧score 2 in IRLS Question 7) Subject has a score of ≧ 4 on the CGI Severity score at baseline Exclusion Criteria: Subject has secondary RLS in association with renal impairment such as uremia，iron deficiency anemia, and drug associated symptoms. Subject has, is suspected of having or has a history of sleep disorders such as sleep apnea syndrome, narcolepsy, sleep attacks/sudden onset of sleep. Subject has additional clinically relevant concomitant diseases or symptoms such as polyneuropathy (including diabetic neuropathy), akathisia，claudication varicoses，muscle fasciculation，painful legs moving toes and radiculopathy. Subject has other central nervous diseases like Parkinson's disease, dimentia, progressive supranuclear paresis, multisystem atrophy, Huntington's Chorea, amyotrophic lateral sclerosis, or Alzheimer's disease. At screening or baseline, subject has psychiatric condition like confusion, hallucination, delusion, excitation, deliria, abnormal behaviour. Subject has orthostatic hypotension or systolic BP marks ≦ 100 mm Hg and with a decrease of BP from supine to standing position of ≧ 30 mm Hg. Subject has a history of epilepsy, convulsion etc. Subject has serious cardiac dysfunction and/or arrhythmias (e.g., congestive heart failure Class III or IV by NYHA, myocardial infarction, angina pectoris, conduction system dysregulations, second or third degree AV block, complete left bundle branch block, sick-sinus-syndrome, ventricular fibrillation within twelve months prior to enrollment). Subject has arrhythmia and receiving Class Ia antiarrhythmic drugs(e.g., quinidine, procainamide), Class III antiarrhythmic drugs (e.g., amiodarone, sotalol) 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 long QT syndrome congenital. Subject has a serum potassium level < 3.5 mEq/L at screening. Subject has a total bilirubin ≧3.0 mg/dL or AST(GOT) and/or ALT(GPT) greater than 2.5 times the upper limit of the reference range (or ≧100 IU/L) at screening. Subject has BUN ≧ 30 mg/dL or serum creatinine ≧2.0 mg/dl at screening. 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 pursues shift work or is subject to other continuous non-disease-related life conditions which do not allow regular sleep at night. Subject has autoimmune disease, chronic active hepatitis or immune deficiency disorder. Subject has a malignant neoplastic disease requiring therapy within twelve months prior to screening. 19. Subject received an investigational drug from other clinical trial within the last 12 months prior to baseline. 20. Subject is judged to be inappropriate for this trial by investigator on the 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>inactive placebo | Drug: SPM 962<br>* transdermal application, 1 time per day, 0-6.75 mg/body, titration, 6weeks<br>* Other names: rotigotine;|
| Experimental: 2<br>2.25 mg first week: 2.25 mg 1 sheet plus placebo 1 sheet 2nd to 6th week :2.25mg 1 sheet plus placebo 2 sheets | Drug: SPM 962<br>* transdermal application, 1 time per day, 0-6.75 mg/body, titration, 6weeks<br>* Other names: rotigotine;|
| Experimental: 3<br>4.5 mg/body first week : 2.25 mg 2 sheets 2nd to 6th week : 2.25 mg 2 sheets pus placebo 1 sheet | Drug: SPM 962<br>* transdermal application, 1 time per day, 0-6.75 mg/body, titration, 6weeks<br>* Other names: rotigotine;|
| Experimental: 4<br>6.75 mg/body first week : 2.25 mg 2 sheets 2nd to 6th week : 2.25 mg 3sheets | Drug: SPM 962<br>* transdermal application, 1 time per day, 0-6.75 mg/body, titration, 6weeks<br>* Other names: rotigotine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score From the Baseline to the End of Titration/Maintenance Period | 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, end of maintenance period at 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Impression (CGI) Severity | CGI is a clinician-reported scale for assessing severity of illness. The sale scoring criteria are 1: Normal, not at all ill, 2: Borderline ill, 3: Mildly ill, 4: Moderately ill, 5: Markedly ill, 6: Severely ill, 7: Among the most extremely ill patients. | Baseline, 2 weeks, 4 weeks and 6 weeks. The data at 6 weeks after dosing is shown. | 
| Patient Global Impression (PGI) Improvement | The PGI-I is a self-rated 7-point scale, with scores ranging from 1 (very much improved) to 7 (very much worse), that assesses the improvement or worsening of a patient's illness relative to baseline at the beginning of the intervention. Scores: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; or 7=very much worse. Moderate and marked improvement = score of 1 or 2, Without improvement = score of 4, Marked and moderate aggravation = score of 6 or 7. | Baseline, 4 weeks and 6 weeks. The data at 6 weeks after dosing is shown. | 
| The Pittsburgh Sleep Quality Index (PSQI) | 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. The data at 6 weeks after dosing is shown. | Baseline, every two weeks | 
| Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Mean Change from baseline in MOS Short Form SF-36 to 6 weeks after dosing. 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, every two weeks | 
| IRLS Each Parameter | 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. The percentage of subjects with -3 or -4 changes from baseline in each parameter at 6 weeks after dosing is shown. | Baseline, every two weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SPM 962, rotigotine, Idiopathic Restless Legs Syndrome, RLS