A Placebo-Controlled Study for SPM 962 in Restless Legs Syndrome (RLS) Patients

Phase 2

Completed

• Conditions: Idiopathic Restless Legs Syndrome
• Interventions: Drug: SPM 962

• Registration Number: NCT00666965
• Lead Sponsor: Otsuka Pharmaceutical Co., Ltd.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2008-04-23
• Study First Submitted QC: 2008-04-24
• Study First Posted: 2008-04-25
• Study Start: 2008-06
• Primary Completion: 2009-08
• Study Completion: 2009-08
• Results First Submitted: 2014-02-03
• Status Verified: 2014-03
• Results First Submitted QC: 2014-03-26
• Last Update Submitted: 2014-03-26
• Results First Posted: 2014-04-25
• Last Update Posted: 2014-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 230

Inclusion Criteria

1. 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.

2. Subject meets the diagnosis of idiopathic RLS based on the 4 cardinal clinical features according to the IRLSSG/NIH.

3. 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.

4. 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)

5. Subject has a score of ≧ 4 on the CGI Severity score at baseline

Exclusion Criteria

1. Subject has secondary RLS in association with renal impairment such as uremia，iron deficiency anemia, and drug associated symptoms.

2. 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.

3. 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.

4. 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.

5. At screening or baseline, subject has psychiatric condition like confusion, hallucination, delusion, excitation, deliria, abnormal behaviour.

6. 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.

7. Subject has a history of epilepsy, convulsion etc.

8. 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).

9. Subject has arrhythmia and receiving Class Ia antiarrhythmic drugs(e.g., quinidine, procainamide), Class III antiarrhythmic drugs (e.g., amiodarone, sotalol)

10. 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.

11. Subject has long QT syndrome congenital.

12. Subject has a serum potassium level < 3.5 mEq/L at screening.

13. 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.

14. Subject has BUN ≧ 30 mg/dL or serum creatinine ≧2.0 mg/dl at screening.

15. Subject has a history of allergic reaction to topical agents such as transdermal patch.

16. Subject is pregnant or nursing or woman who plans pregnancy during the trial.

17. Subject pursues shift work or is subject to other continuous non-disease-related life conditions which do not allow regular sleep at night.

18. Subject has autoimmune disease, chronic active hepatitis or immune deficiency disorder.

19. Subject has a malignant neoplastic disease requiring therapy within twelve months prior to screening.

20. Subject received an investigational drug from other clinical trial within the last 12 months prior to baseline.

21. Subject is judged to be inappropriate for this trial by investigator on the other than above.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	SPM 962	inactive placebo
3	SPM 962	4.5 mg/body first week : 2.25 mg 2 sheets 2nd to 6th week : 2.25 mg 2 sheets pus placebo 1 sheet
2	SPM 962	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
4	SPM 962	6.75 mg/body first week : 2.25 mg 2 sheets 2nd to 6th week : 2.25 mg 3sheets

Primary Outcome Measures

Name	Time	Method
Change of International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score From the Baseline to the End of Titration/Maintenance Period	Baseline, end of maintenance period at 6 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Patient Global Impression (PGI) Improvement	Baseline, 4 weeks and 6 weeks. The data at 6 weeks after dosing is shown.	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.
IRLS Each Parameter	Baseline, every two weeks	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.
Clinical Global Impression (CGI) Severity	Baseline, 2 weeks, 4 weeks and 6 weeks. The data at 6 weeks after dosing is shown.	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.
The Pittsburgh Sleep Quality Index (PSQI)	Baseline, every two weeks	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.
Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36)	Baseline, every two weeks	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.