Study of SPM 962 in Patients With Restless Legs Syndrome (RLS)

A Phase 3 Multi-Center, Placebo-Controlled, Double Blind, 3-Armed Parallel Group, Comparative Study of SPM 962 4.5 and 6.75 mg/Day to Investigate Superiority to Placebo in Patients With Restless Legs Syndrome

The objective of this study is to evaluate the clinical efficacy and safety of SPM962 in patients with restless legs syndrome (RLS) with once-daily repeated doses of 4.5mg and 6.75mg during a 13-week dose-titration and maintenance period. This is a multi-center, randomized, placebo-controlled, double-blind, 3-armed parallel group comparison study.

Efficacy will be determined by investigating the superiority of SPM962 to placebo in terms of the primary efficacy variable, change in International Restless Legs Syndrome Rating Scale (IRLS) total score from baseline to the end of the dose-maintenance period.

Inclusion Criteria:

• Patients whose condition has been diagnosed as RLS by meeting all 4 of the International Restless legs Syndrome Study Group/ National Institute of Health (IRLSSG/NIH) criteria

• Patients who meet any of the following criteria relating to RLS treatment:

  • Patients who have never received treatment for RLS
  • Patients who have received treatment for RLS in the past and responded to L-dopa or dopamine agonists (Response to other RLS medicines is irrelevant.)

• Patients who have an IRLS total score of >=15 at baseline

• Patients who experience symptoms in the evening or during the night on at least two days a week within 14 days prior to commencement of study treatment

• Patients and their partners can practice contraception at the end of follow-up observation period or by 1 week after the end of treatment

Exclusion Criteria:

• Patients who have previously participated in a clinical trial of SPM962 and taken the investigational product (IP)

• Patients with secondary RLS induced by renal impairment (uremia), iron deficiency anemia, drugs, pregnancy, etc.

• Patients who currently suffer, are at risk of developing, or have a history of sleep disorder such as sleep apnea syndrome, narcolepsy, and sleep attacks/sudden onset of sleep

• Patients who have concomitant diseases or symptoms which may affect the symptoms of RLS, such as polyneuropathy (including diabetic neuropathy), akathisia, claudication, varicoses, muscle fasciculation, painful legs and moving toes syndrome, radiculopathy and folate deficiency

• Patients who have other CNS diseases such as Parkinson's disease, dementia, progressive supranuclear paresis, multisystem atrophy, Huntington's Chorea, amyotrophic lateral sclerosis, and Alzheimer's disease

• Patients who have psychiatric conditions such as confusion, hallucination, delusion, and excitation, or patients who have abnormal behavior such as delirium, obsessive compulsive disorder, and impulse control disorder at the time of the screening test or baseline examination

• Patients whose SBP declines by at least 30 mmHg from supine to standing position based on the orthostatic hypotension assessment, or patients who develop orthostatic hypotension at baseline

• Patients who have a history of epilepsy, convulsion, etc

• Patients who have complications or a history of serious cardiac diseases or arrhythmia (eg, congestive heart failure of class 3 or 4 in the NYHA classification, second or third degree atrioventricular block, complete left bundle branch block, sick sinus syndrome, ventricular fibrillation, myocardial infarction within 12 months prior to the screening test, or a complication of angina pectoris)

• Patients with arrhythmia who have been taking Class 1a antiarrhythmic drugs (eg., quinidine, procainamide) or Class 3 antiarrhythmic drugs (eg., amiodarone, sotalol)

• Patients who have a serious ECG abnormality at the screening test and at the baseline examination

  • Patients who show QTc intervals exceeding 450 ms in both ECGs in the screening test
  • Patients who have an average QTc interval from the two ECGs in the baseline assessment that exceeds 470 ms (for females) or 450 ms (for males)

• Patients with congenital long QT syndrome

• Patients whose serum potassium level is < 3.5mEq/L at the screening test

• Patients whose total bilirubin is >= 3.0mg/dL, or whose AST(GOT) and ALT(GPT) are equal or more than 2.5 times the reference range of the clinical site (or >= 100IU/L) at the screening test

• Patients whose BUN level is >= 30mg/dL, or whose serum creatinine level is >= 2.0mg/dL at the screening test

• Patients who have a history of allergy to topical agents such as transdermal patch

• Patients who are pregnant or nursing or who wish to become pregnant during the study period

• Patients who habitually drink alcohol or smoke excessively

• Patients who engage in evening shift work or other such shift work, or whose work or circumstances makes it difficult to maintain a regular period of sleep

• Patients who engage in hazardous work such as driving a vehicle, operating machinery, or working in a high location.

• Patients with autoimmune disease, chronic active hepatitis, or immune deficiency disorder

• Patients who have a complication or history of malignant neoplastic disease, or received treatment for the disease within 12 months prior to the screening test

• Patients who are unable to properly record information in a patient diary

• Patients who received other IPs within 12 weeks prior to commencement of study treatment

• Patients who have been judged by the investigator or the sub-investigator to be inappropriate for inclusion in the study for any other reasons