Idiopathic Restless Legs Syndrome
Conditions
Keywords
SPM 962, rotigotine, Idiopathic Restless Legs Syndrome, RLS
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.
Interventions
DRUGSPM 962
transdermal application, 1 time per day, 0-6.75 mg/body, titration, 6weeks
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
20 Years to 79 Years
Healthy volunteers
No
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. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo placebo transdermal patch | 57 |
| 2.25 mg/Day SPM962 maintein dose: 2.25 mg/day | 57 |
| 4.5 mg/Day SPM962 maintein dose: 4.5mg/day | 57 |
| 6.75 mg/Day SPM962 maintein dose: 6.75 mg/day | 56 |
| Total | 227 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 1 | 9 |
| Overall Study | Discontinuation criteria | 2 | 1 | 1 | 2 |
| Overall Study | Lack of Efficacy | 1 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | 2.25 mg/Day | 4.5 mg/Day | Placebo | 6.75 mg/Day | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 8 Participants | 9 Participants | 8 Participants | 34 Participants |
| Age, Categorical Between 18 and 65 years | 48 Participants | 49 Participants | 48 Participants | 48 Participants | 193 Participants |
| Age, Continuous | 50.6 years STANDARD_DEVIATION 13 | 48.3 years STANDARD_DEVIATION 14.1 | 48.6 years STANDARD_DEVIATION 13.1 | 51.0 years STANDARD_DEVIATION 12.4 | 49.6 years STANDARD_DEVIATION 13.1 |
| Region of Enrollment Japan | 57 participants | 57 participants | 57 participants | 56 participants | 227 participants |
| Sex: Female, Male Female | 41 Participants | 33 Participants | 37 Participants | 32 Participants | 143 Participants |
| Sex: Female, Male Male | 16 Participants | 24 Participants | 20 Participants | 24 Participants | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 29 / 58 | 37 / 57 | 50 / 58 | 44 / 57 |
| serious Total, serious adverse events | 0 / 58 | 0 / 57 | 0 / 58 | 0 / 57 |
Outcome results
Primary
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.
Time frame: Baseline, end of maintenance period at 6 weeks
Population: Full analysis set (FAS), last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change of International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score From the Baseline to the End of Titration/Maintenance Period | -9.8 scores on a scale | Standard Deviation 7.2 |
| 2.25 mg/Day | Change of International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score From the Baseline to the End of Titration/Maintenance Period | -10.7 scores on a scale | Standard Deviation 6.3 |
| 4.5 mg/Day | Change of International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score From the Baseline to the End of Titration/Maintenance Period | -14.4 scores on a scale | Standard Deviation 7.2 |
| 6.75 mg/Day | Change of International Restless Legs Syndrome Study Group Rating Scale (IRLS) Score From the Baseline to the End of Titration/Maintenance Period | -14.1 scores on a scale | Standard Deviation 8.8 |
Secondary
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.
Time frame: Baseline, 2 weeks, 4 weeks and 6 weeks. The data at 6 weeks after dosing is shown.
Population: FAS, LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Clinical Global Impression (CGI) Severity | Decreased | 73.7 Percentage of Participants |
| Placebo | Clinical Global Impression (CGI) Severity | 4 at baseline and stayed at 4 | 26.5 Percentage of Participants |
| Placebo | Clinical Global Impression (CGI) Severity | Subjects without improvement | 26.3 Percentage of Participants |
| Placebo | Clinical Global Impression (CGI) Severity | Increased | 1.8 Percentage of Participants |
| Placebo | Clinical Global Impression (CGI) Severity | 5 at baseline and decreased to 1 or 2 | 0 Percentage of Participants |
| Placebo | Clinical Global Impression (CGI) Severity | Decreased to 1 or 2 | 12.3 Percentage of Participants |
| Placebo | Clinical Global Impression (CGI) Severity | Subjects with CGI score 5 | 8.8 Percentage of Participants |
| 2.25 mg/Day | Clinical Global Impression (CGI) Severity | 4 at baseline and stayed at 4 | 13.3 Percentage of Participants |
| 2.25 mg/Day | Clinical Global Impression (CGI) Severity | Subjects with CGI score 5 | 12.7 Percentage of Participants |
| 2.25 mg/Day | Clinical Global Impression (CGI) Severity | Decreased to 1 or 2 | 18.2 Percentage of Participants |
| 2.25 mg/Day | Clinical Global Impression (CGI) Severity | Subjects without improvement | 16.4 Percentage of Participants |
| 2.25 mg/Day | Clinical Global Impression (CGI) Severity | 5 at baseline and decreased to 1 or 2 | 24.0 Percentage of Participants |
| 2.25 mg/Day | Clinical Global Impression (CGI) Severity | Increased | 1.8 Percentage of Participants |
| 2.25 mg/Day | Clinical Global Impression (CGI) Severity | Decreased | 83.6 Percentage of Participants |
| 4.5 mg/Day | Clinical Global Impression (CGI) Severity | Subjects with CGI score 5 | 3.6 Percentage of Participants |
| 4.5 mg/Day | Clinical Global Impression (CGI) Severity | Decreased | 92.9 Percentage of Participants |
| 4.5 mg/Day | Clinical Global Impression (CGI) Severity | Increased | 0.0 Percentage of Participants |
| 4.5 mg/Day | Clinical Global Impression (CGI) Severity | Decreased to 1 or 2 | 41.1 Percentage of Participants |
| 4.5 mg/Day | Clinical Global Impression (CGI) Severity | Subjects without improvement | 7.1 Percentage of Participants |
| 4.5 mg/Day | Clinical Global Impression (CGI) Severity | 4 at baseline and stayed at 4 | 10.7 Percentage of Participants |
| 4.5 mg/Day | Clinical Global Impression (CGI) Severity | 5 at baseline and decreased to 1 or 2 | 46.4 Percentage of Participants |
| 6.75 mg/Day | Clinical Global Impression (CGI) Severity | Decreased to 1 or 2 | 39.2 Percentage of Participants |
| 6.75 mg/Day | Clinical Global Impression (CGI) Severity | 5 at baseline and decreased to 1 or 2 | 30.4 Percentage of Participants |
| 6.75 mg/Day | Clinical Global Impression (CGI) Severity | 4 at baseline and stayed at 4 | 10.7 Percentage of Participants |
| 6.75 mg/Day | Clinical Global Impression (CGI) Severity | Increased | 3.9 Percentage of Participants |
| 6.75 mg/Day | Clinical Global Impression (CGI) Severity | Decreased | 86.3 Percentage of Participants |
| 6.75 mg/Day | Clinical Global Impression (CGI) Severity | Subjects without improvement | 13.7 Percentage of Participants |
| 6.75 mg/Day | Clinical Global Impression (CGI) Severity | Subjects with CGI score 5 | 7.8 Percentage of Participants |
Secondary
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.
Time frame: Baseline, every two weeks
Population: FAS, LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | IRLS Each Parameter | -3 (tiredness or sleepiness during the day) | 1.8 Percentage of Participants |
| Placebo | IRLS Each Parameter | -4 (average duration of RLS symptoms) | 0.0 Percentage of Participants |
| Placebo | IRLS Each Parameter | -3 (average duration of RLS symptoms) | 3.5 Percentage of Participants |
| Placebo | IRLS Each Parameter | -4 (tiredness or sleepiness during the day) | 0.0 Percentage of Participants |
| Placebo | IRLS Each Parameter | -4 (severity of sleep disturbance) | 0.0 Percentage of Participants |
| Placebo | IRLS Each Parameter | -3 (need to move around due to RLS symptoms) | 10.5 Percentage of Participants |
| Placebo | IRLS Each Parameter | -3 (severity of sleep disturbance) | 3.5 Percentage of Participants |
| Placebo | IRLS Each Parameter | -4 (severity of mood disturbance) | 0.0 Percentage of Participants |
| Placebo | IRLS Each Parameter | -4 (discomfort relief by moving around) | 0.0 Percentage of Participants |
| Placebo | IRLS Each Parameter | -3 (RLS discomfort) | 7.0 Percentage of Participants |
| Placebo | IRLS Each Parameter | -3 (discomfort relief by moving around) | 7.0 Percentage of Participants |
| Placebo | IRLS Each Parameter | -3 (severity of impact on daily affaires) | 5.3 Percentage of Participants |
| Placebo | IRLS Each Parameter | -4 (severity of RLS as a whole) | 0.0 Percentage of Participants |
| Placebo | IRLS Each Parameter | -4 (RLS discomfort) | 0.0 Percentage of Participants |
| Placebo | IRLS Each Parameter | -3 (severity of RLS as a whole) | 1.8 Percentage of Participants |
| Placebo | IRLS Each Parameter | -3 (severity of mood disturbance) | 5.3 Percentage of Participants |
| Placebo | IRLS Each Parameter | -4 (need to move around due to RLS symptoms) | 0.0 Percentage of Participants |
| Placebo | IRLS Each Parameter | -4 (severity of impact on daily affaires) | 0.0 Percentage of Participants |
| Placebo | IRLS Each Parameter | -4 (RLS symptoms frequency) | 1.8 Percentage of Participants |
| Placebo | IRLS Each Parameter | -3 (RLS symptoms frequency) | 7.0 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -4 (need to move around due to RLS symptoms) | 0.0 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -3 (discomfort relief by moving around) | 9.1 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -4 (average duration of RLS symptoms) | 0.0 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -4 (severity of mood disturbance) | 0.0 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -4 (tiredness or sleepiness during the day) | 0.0 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -3 (RLS discomfort) | 1.8 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -3 (average duration of RLS symptoms) | 0.0 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -3 (tiredness or sleepiness during the day) | 7.3 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -4 (RLS discomfort) | 0.0 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -4 (severity of sleep disturbance) | 0.0 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -4 (severity of RLS as a whole) | 0.0 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -3 (severity of sleep disturbance) | 12.7 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -3 (RLS symptoms frequency) | 7.3 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -3 (need to move around due to RLS symptoms) | 9.1 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -3 (severity of mood disturbance) | 5.5 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -4 (severity of impact on daily affaires) | 1.8 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -4 (RLS symptoms frequency) | 3.6 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -4 (discomfort relief by moving around) | 0.0 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -3 (severity of RLS as a whole) | 3.6 Percentage of Participants |
| 2.25 mg/Day | IRLS Each Parameter | -3 (severity of impact on daily affaires) | 3.6 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -4 (need to move around due to RLS symptoms) | 3.6 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -3 (RLS discomfort) | 16.1 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -4 (RLS discomfort) | 0.0 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -3 (need to move around due to RLS symptoms) | 16.1 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -4 (discomfort relief by moving around) | 1.8 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -3 (discomfort relief by moving around) | 26.8 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -4 (severity of RLS as a whole) | 0.0 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -3 (severity of RLS as a whole) | 12.5 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -3 (average duration of RLS symptoms) | 7.1 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -4 (RLS symptoms frequency) | 3.6 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -3 (RLS symptoms frequency) | 26.8 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -4 (average duration of RLS symptoms) | 0.0 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -4 (severity of sleep disturbance) | 1.8 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -3 (severity of sleep disturbance) | 12.5 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -4 (tiredness or sleepiness during the day) | 0.0 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -3 (tiredness or sleepiness during the day) | 5.4 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -4 (severity of impact on daily affaires) | 1.8 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -3 (severity of impact on daily affaires) | 3.6 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -4 (severity of mood disturbance) | 1.8 Percentage of Participants |
| 4.5 mg/Day | IRLS Each Parameter | -3 (severity of mood disturbance) | 1.8 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -3 (RLS symptoms frequency) | 19.6 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -4 (RLS symptoms frequency) | 9.8 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -4 (severity of mood disturbance) | 0.0 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -3 (tiredness or sleepiness during the day) | 11.8 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -3 (severity of RLS as a whole) | 19.6 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -4 (severity of RLS as a whole) | 2.0 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -3 (RLS discomfort) | 19.6 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -4 (severity of impact on daily affaires) | 2.0 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -3 (discomfort relief by moving around) | 13.7 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -4 (discomfort relief by moving around) | 2.0 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -4 (RLS discomfort) | 3.9 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -3 (severity of impact on daily affaires) | 7.8 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -3 (need to move around due to RLS symptoms) | 25.5 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -4 (severity of sleep disturbance) | 2.0 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -4 (need to move around due to RLS symptoms) | 2.0 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -3 (severity of sleep disturbance) | 21.6 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -3 (average duration of RLS symptoms) | 7.8 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -4 (average duration of RLS symptoms) | 0.0 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -3 (severity of mood disturbance) | 7.8 Percentage of Participants |
| 6.75 mg/Day | IRLS Each Parameter | -4 (tiredness or sleepiness during the day) | 0.0 Percentage of Participants |
Secondary
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.
Time frame: Baseline, every two weeks
Population: FAS, LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Physical functioning | 1.1 Scores on a scale | Standard Deviation 8.1 |
| Placebo | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Social functioning | -0.2 Scores on a scale | Standard Deviation 19.3 |
| Placebo | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Vitality | 6.3 Scores on a scale | Standard Deviation 16.6 |
| Placebo | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Role physical | -0.4 Scores on a scale | Standard Deviation 18 |
| Placebo | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Role emotional | -0.1 Scores on a scale | Standard Deviation 18.4 |
| Placebo | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Bodily pain | -1.7 Scores on a scale | Standard Deviation 25 |
| Placebo | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | General health | 3.4 Scores on a scale | Standard Deviation 16.4 |
| 2.25 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Social functioning | 4.4 Scores on a scale | Standard Deviation 17 |
| 2.25 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | General health | 2.5 Scores on a scale | Standard Deviation 10.5 |
| 2.25 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Bodily pain | 5.0 Scores on a scale | Standard Deviation 28 |
| 2.25 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Vitality | 6.5 Scores on a scale | Standard Deviation 17.2 |
| 2.25 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Role emotional | 5.7 Scores on a scale | Standard Deviation 18.4 |
| 2.25 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Role physical | 1.7 Scores on a scale | Standard Deviation 18.7 |
| 2.25 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Physical functioning | 1.6 Scores on a scale | Standard Deviation 9.6 |
| 4.5 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | General health | 4.6 Scores on a scale | Standard Deviation 14.8 |
| 4.5 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Physical functioning | 2.8 Scores on a scale | Standard Deviation 12.7 |
| 4.5 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Role physical | 1.3 Scores on a scale | Standard Deviation 15.8 |
| 4.5 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Bodily pain | 1.7 Scores on a scale | Standard Deviation 27.4 |
| 4.5 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Vitality | 3.6 Scores on a scale | Standard Deviation 19.9 |
| 4.5 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Social functioning | 1.1 Scores on a scale | Standard Deviation 18.4 |
| 4.5 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Role emotional | 4.2 Scores on a scale | Standard Deviation 18.7 |
| 6.75 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Bodily pain | 12.6 Scores on a scale | Standard Deviation 19.7 |
| 6.75 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Role emotional | 0.7 Scores on a scale | Standard Deviation 16.6 |
| 6.75 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Social functioning | 4.0 Scores on a scale | Standard Deviation 12.5 |
| 6.75 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Role physical | 0.9 Scores on a scale | Standard Deviation 11.9 |
| 6.75 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Physical functioning | 0.1 Scores on a scale | Standard Deviation 6.1 |
| 6.75 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | Vitality | 6.5 Scores on a scale | Standard Deviation 18.6 |
| 6.75 mg/Day | Medical Outcome Study (MOS) Short-Form 36-Item Health Survey (SF-36) | General health | 4.9 Scores on a scale | Standard Deviation 12.9 |
Secondary
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.
Time frame: Baseline, 4 weeks and 6 weeks. The data at 6 weeks after dosing is shown.
Population: FAS, LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Patient Global Impression (PGI) Improvement | Moderate and marked improvement | 55.4 Percentage of Participants |
| Placebo | Patient Global Impression (PGI) Improvement | Moderate and marked aggravation | 0.0 Percentage of Participants |
| Placebo | Patient Global Impression (PGI) Improvement | Without improvement | 17.9 Percentage of Participants |
| 2.25 mg/Day | Patient Global Impression (PGI) Improvement | Moderate and marked improvement | 70.4 Percentage of Participants |
| 2.25 mg/Day | Patient Global Impression (PGI) Improvement | Moderate and marked aggravation | 0.0 Percentage of Participants |
| 2.25 mg/Day | Patient Global Impression (PGI) Improvement | Without improvement | 3.7 Percentage of Participants |
| 4.5 mg/Day | Patient Global Impression (PGI) Improvement | Without improvement | 3.6 Percentage of Participants |
| 4.5 mg/Day | Patient Global Impression (PGI) Improvement | Moderate and marked improvement | 82.1 Percentage of Participants |
| 4.5 mg/Day | Patient Global Impression (PGI) Improvement | Moderate and marked aggravation | 1.8 Percentage of Participants |
| 6.75 mg/Day | Patient Global Impression (PGI) Improvement | Moderate and marked improvement | 85.4 Percentage of Participants |
| 6.75 mg/Day | Patient Global Impression (PGI) Improvement | Moderate and marked aggravation | 0.0 Percentage of Participants |
| 6.75 mg/Day | Patient Global Impression (PGI) Improvement | Without improvement | 6.3 Percentage of Participants |
Secondary
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.
Time frame: Baseline, every two weeks
Population: FAS, LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | The Pittsburgh Sleep Quality Index (PSQI) | Subjects with ≥60% decrease | 7.1 Percentage of Participants |
| Placebo | The Pittsburgh Sleep Quality Index (PSQI) | Subjects with ≥50% decrease | 25.0 Percentage of Participants |
| 2.25 mg/Day | The Pittsburgh Sleep Quality Index (PSQI) | Subjects with ≥50% decrease | 27.8 Percentage of Participants |
| 2.25 mg/Day | The Pittsburgh Sleep Quality Index (PSQI) | Subjects with ≥60% decrease | 16.7 Percentage of Participants |
| 4.5 mg/Day | The Pittsburgh Sleep Quality Index (PSQI) | Subjects with ≥60% decrease | 23.2 Percentage of Participants |
| 4.5 mg/Day | The Pittsburgh Sleep Quality Index (PSQI) | Subjects with ≥50% decrease | 39.3 Percentage of Participants |
| 6.75 mg/Day | The Pittsburgh Sleep Quality Index (PSQI) | Subjects with ≥60% decrease | 23.4 Percentage of Participants |
| 6.75 mg/Day | The Pittsburgh Sleep Quality Index (PSQI) | Subjects with ≥50% decrease | 44.7 Percentage of Participants |