Idiopathic Restless Legs Syndrome
Conditions
Brief summary
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.
Interventions
DRUGSPM 962
once a daily transdermal administration started at 2.25 mg/day to 4.5 mg/day for 13 weeks
DRUGPlacebo of SPM 962
once a daily transdermal administration for 13 weeks
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| International Restless Legs Syndrome Rating Scale (IRLS) Total Score | Baseline, the end of dose-titration/dose-maintenance period (week 13) | Change from the baseline to the end of dose-titration/dose-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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression (CGI) Improvement | Baseline, the end of dose-titration/dose-maintenance period (week 13) | CGI improvement is a clinician-reported scale for assessing how much the patient's illness has improved or worsened from baseline. The scale scoring criteria are 1: very much improved, 2: much improved, 3: minimally improved, 4: no change, 5: minimally worse, 6: much worse, 7: very much worse. |
| Patient Global Impression (PGI) Improvement | Baseline, the end of dose-titration/dose-maintenance period (week 13) | PGI improvement is a patient-reported scale for assessing how much the patient's illness has improved or worsened from baseline. The scale scoring criteria are 1: very much better, 2: much better, 3: a little better, 4: no change, 5: a little worse, 6: much worse, 7: very much worse. |
| The Pittsburgh Sleep Quality Index (PSQI) | Baseline, the end of dose-titration/dose-maintenance period (week 13) | Change of PSQI from baseline to the end of dose-titration/dose-maintenance period. 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. |
| Each Item of IRLS (10 Items) | Baseline, the end of dose-titration/dose-maintenance period (week 13) | 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). Numbers of subjects with -4 or -3 score change from baseline in each item of IRLS. A decrease in the scores means improvement. |
| Average Duration of RLS Symptoms | Baseline, the end of dose-titration/dose-maintenance period (weeks 13) | Change of average duration of RLS symptoms in a week from baseline to the end of dose-titration/dose-maintenance period. Only the days with RLS symptoms are used for calculation. |
| Incidence of RLS Symptoms in the Evening and Night | Baseline, the end of dose-titration/dose-maintenance period (week 13) | Incidence rate of RLS symptoms is calculated as the number of days with RLS symptoms / the number of days of evaluation \* 100%. |
| Average Duration of RLS Symptoms in the Evening and Night in a Week | Baseline, the end of dose-titration/dose-maintenance period (weeks 13) | Change of average duration of RLS symptoms in a week from baseline to the end of dose-titration/dose-maintenance period. Only the days with RLS symptoms are used for calculation. |
| Nocturnal Awakenings Due to RLS Symptoms in a Week | Baseline, the end of dose-titration/dose-maintenance period (week 13) | Nocturnal awakening rate is calculated as the number of days with nocturnal awakenings / the number of days of evaluation \* 100%. |
| Average Sleep Time in a Week | Baseline, the end of dose-titration/dose-maintenance period (weeks 13) | Change of average sleep time in a week from baseline to the end of dose-titration/dose-maintenance period. |
| Incidence of RLS Symptoms | Baseline, the end of dose-titration/dose-maintenance period (week 13) | Incidence rate of RLS symptoms is calculated as the number of days with RLS symptoms in the week / the number of evaluation days in the week\* 100% |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo 0 mg/day for 13 weeks | 95 |
| SPM 962 4.5 started at 2.25 mg/day to 4.5 mg/day for 13 weeks | 95 |
| SPM 962 6.75 started at 2.25 mg/day to 6.75 mg/day for 13 weeks | 94 |
| Total | 284 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 9 | 4 |
| Overall Study | Lack of Efficacy | 2 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 3 |
| Overall Study | Physician Decision | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 2 | 4 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | SPM 962 4.5 | SPM 962 6.75 | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 30 Participants | 18 Participants | 17 Participants | 65 Participants |
| Age, Categorical Between 18 and 65 years | 65 Participants | 77 Participants | 77 Participants | 219 Participants |
| Age, Continuous | 53.4 years STANDARD_DEVIATION 15.3 | 50.7 years STANDARD_DEVIATION 13.3 | 50.9 years STANDARD_DEVIATION 13.7 | 51.7 years STANDARD_DEVIATION 14.1 |
| Region of Enrollment Japan | 95 participants | 95 participants | 94 participants | 284 participants |
| Sex: Female, Male Female | 54 Participants | 54 Participants | 46 Participants | 154 Participants |
| Sex: Female, Male Male | 41 Participants | 41 Participants | 48 Participants | 130 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 32 / 95 | 72 / 95 | 77 / 94 |
| serious Total, serious adverse events | 2 / 95 | 0 / 95 | 1 / 94 |
Outcome results
Primary
International Restless Legs Syndrome Rating Scale (IRLS) Total Score
Change from the baseline to the end of dose-titration/dose-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, the end of dose-titration/dose-maintenance period (week 13)
Population: Full analysis set (FAS), last observation carried forward (LOCF)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | International Restless Legs Syndrome Rating Scale (IRLS) Total Score | -11.6 Scores on a scale | Standard Deviation 8.2 |
| SPM 962 4.5 | International Restless Legs Syndrome Rating Scale (IRLS) Total Score | -14.3 Scores on a scale | Standard Deviation 8.9 |
| SPM 962 6.75 | International Restless Legs Syndrome Rating Scale (IRLS) Total Score | -14.6 Scores on a scale | Standard Deviation 9 |
Secondary
Average Duration of RLS Symptoms
Change of average duration of RLS symptoms in a week from baseline to the end of dose-titration/dose-maintenance period. Only the days with RLS symptoms are used for calculation.
Time frame: Baseline, the end of dose-titration/dose-maintenance period (weeks 13)
Population: FAS, LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Average Duration of RLS Symptoms | -3.1 Hours | Standard Deviation 4.7 |
| SPM 962 4.5 | Average Duration of RLS Symptoms | -3.7 Hours | Standard Deviation 4.6 |
| SPM 962 6.75 | Average Duration of RLS Symptoms | -4.3 Hours | Standard Deviation 4.4 |
Secondary
Average Duration of RLS Symptoms in the Evening and Night in a Week
Change of average duration of RLS symptoms in a week from baseline to the end of dose-titration/dose-maintenance period. Only the days with RLS symptoms are used for calculation.
Time frame: Baseline, the end of dose-titration/dose-maintenance period (weeks 13)
Population: FAS, LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Average Duration of RLS Symptoms in the Evening and Night in a Week | -1.3 Hours | Standard Deviation 3.1 |
| SPM 962 4.5 | Average Duration of RLS Symptoms in the Evening and Night in a Week | -1.8 Hours | Standard Deviation 2.5 |
| SPM 962 6.75 | Average Duration of RLS Symptoms in the Evening and Night in a Week | -1.5 Hours | Standard Deviation 2.3 |
Secondary
Average Sleep Time in a Week
Change of average sleep time in a week from baseline to the end of dose-titration/dose-maintenance period.
Time frame: Baseline, the end of dose-titration/dose-maintenance period (weeks 13)
Population: FAS, LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Average Sleep Time in a Week | 0.4 Hours | Standard Deviation 0.8 |
| SPM 962 4.5 | Average Sleep Time in a Week | 0.5 Hours | Standard Deviation 1.1 |
| SPM 962 6.75 | Average Sleep Time in a Week | 0.4 Hours | Standard Deviation 1.1 |
Secondary
Clinical Global Impression (CGI) Improvement
CGI improvement is a clinician-reported scale for assessing how much the patient's illness has improved or worsened from baseline. The scale scoring criteria are 1: very much improved, 2: much improved, 3: minimally improved, 4: no change, 5: minimally worse, 6: much worse, 7: very much worse.
Time frame: Baseline, the end of dose-titration/dose-maintenance period (week 13)
Population: FAS, LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Clinical Global Impression (CGI) Improvement | Subjects with much improved | 24.2 Percentage of Participants |
| Placebo | Clinical Global Impression (CGI) Improvement | Subjects with very much improved | 33.7 Percentage of Participants |
| SPM 962 4.5 | Clinical Global Impression (CGI) Improvement | Subjects with much improved | 25.8 Percentage of Participants |
| SPM 962 4.5 | Clinical Global Impression (CGI) Improvement | Subjects with very much improved | 41.9 Percentage of Participants |
| SPM 962 6.75 | Clinical Global Impression (CGI) Improvement | Subjects with much improved | 29.0 Percentage of Participants |
| SPM 962 6.75 | Clinical Global Impression (CGI) Improvement | Subjects with very much improved | 45.2 Percentage of Participants |
Secondary
Each Item of IRLS (10 Items)
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). Numbers of subjects with -4 or -3 score change from baseline in each item of IRLS. A decrease in the scores means improvement.
Time frame: Baseline, the end of dose-titration/dose-maintenance period (week 13)
Population: FAS, LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Each Item of IRLS (10 Items) | -3 (severity of sleep disturbance) | 16.8 percentage of participants |
| Placebo | Each Item of IRLS (10 Items) | -3 (severity of RLS as a whole) | 6.3 percentage of participants |
| Placebo | Each Item of IRLS (10 Items) | -3 (severity of mood disturbance) | 8.4 percentage of participants |
| Placebo | Each Item of IRLS (10 Items) | -4 (severity of sleep disturbance) | 2.1 percentage of participants |
| Placebo | Each Item of IRLS (10 Items) | -4 (RLS symptoms frequency) | 12.6 percentage of participants |
| Placebo | Each Item of IRLS (10 Items) | -3 (severity of the impact on daily affairs) | 8.4 percentage of participants |
| Placebo | Each Item of IRLS (10 Items) | -3 (average duration of RLS symptoms) | 6.3 percentage of participants |
| Placebo | Each Item of IRLS (10 Items) | -3 (RLS symptoms frequency) | 12.6 percentage of participants |
| Placebo | Each Item of IRLS (10 Items) | -3 (need to move around due to RLS symptoms) | 11.6 percentage of participants |
| Placebo | Each Item of IRLS (10 Items) | -4 (average duration of RLS symptoms) | 1.1 percentage of participants |
| Placebo | Each Item of IRLS (10 Items) | -3 (RLS discomfort) | 11.6 percentage of participants |
| Placebo | Each Item of IRLS (10 Items) | -4 (severity of the impact on daily affairs) | 0 percentage of participants |
| Placebo | Each Item of IRLS (10 Items) | -4 (discomfort relief by moving around) | 0 percentage of participants |
| Placebo | Each Item of IRLS (10 Items) | -4 (RLS discomfort) | 1.1 percentage of participants |
| Placebo | Each Item of IRLS (10 Items) | -3 (tiredness or sleepiness during the day) | 8.4 percentage of participants |
| Placebo | Each Item of IRLS (10 Items) | -3 (discomfort relief by moving around) | 10.5 percentage of participants |
| Placebo | Each Item of IRLS (10 Items) | -4 (severity of mood disturbance) | 1.1 percentage of participants |
| Placebo | Each Item of IRLS (10 Items) | -4 (tiredness or sleepiness during the day) | 0 percentage of participants |
| Placebo | Each Item of IRLS (10 Items) | -4 (severity of RLS as a whole) | 1.1 percentage of participants |
| Placebo | Each Item of IRLS (10 Items) | -4 (need to move around due to RLS symptoms) | 2.1 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -3 (severity of the impact on daily affairs) | 11.8 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -3 (RLS discomfort) | 17.2 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -4 (need to move around due to RLS symptoms) | 2.2 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -3 (need to move around due to RLS symptoms) | 25.8 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -4 (discomfort relief by moving around) | 1.1 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -3 (discomfort relief by moving around) | 20.4 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -4 (severity of RLS as a whole) | 1.1 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -3 (severity of RLS as a whole) | 12.9 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -4 (RLS symptoms frequency) | 24.7 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -3 (RLS symptoms frequency) | 9.7 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -4 (average duration of RLS symptoms) | 2.2 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -3 (average duration of RLS symptoms) | 10.8 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -4 (severity of sleep disturbance) | 4.3 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -3 (severity of sleep disturbance) | 16.1 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -4 (tiredness or sleepiness during the day) | 2.2 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -3 (tiredness or sleepiness during the day) | 11.8 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -4 (severity of the impact on daily affairs) | 1.1 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -4 (RLS discomfort) | 2.2 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -4 (severity of mood disturbance) | 4.3 percentage of participants |
| SPM 962 4.5 | Each Item of IRLS (10 Items) | -3 (severity of mood disturbance) | 10.8 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -3 (severity of the impact on daily affairs) | 4.3 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -3 (severity of sleep disturbance) | 21.3 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -3 (discomfort relief by moving around) | 28.7 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -3 (RLS discomfort) | 12.8 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -4 (tiredness or sleepiness during the day) | 2.1 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -4 (discomfort relief by moving around) | 2.1 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -3 (severity of mood disturbance) | 12.8 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -3 (tiredness or sleepiness during the day) | 8.5 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -3 (need to move around due to RLS symptoms) | 18.1 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -4 (severity of mood disturbance) | 1.1 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -3 (RLS symptoms frequency) | 11.7 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -4 (severity of the impact on daily affairs) | 1.1 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -4 (average duration of RLS symptoms) | 2.1 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -4 (RLS symptoms frequency) | 26.6 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -4 (need to move around due to RLS symptoms) | 7.4 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -3 (average duration of RLS symptoms) | 9.6 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -3 (severity of RLS as a whole) | 12.8 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -4 (RLS discomfort) | 6.4 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -4 (severity of sleep disturbance) | 6.4 percentage of participants |
| SPM 962 6.75 | Each Item of IRLS (10 Items) | -4 (severity of RLS as a whole) | 4.3 percentage of participants |
Secondary
Incidence of RLS Symptoms
Incidence rate of RLS symptoms is calculated as the number of days with RLS symptoms in the week / the number of evaluation days in the week\* 100%
Time frame: Baseline, the end of dose-titration/dose-maintenance period (week 13)
Population: FAS, LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Incidence of RLS Symptoms | Baseline | 85.7 percentage of days with RLS symptom | Standard Deviation 20.8 |
| Placebo | Incidence of RLS Symptoms | Week 13 | 48.7 percentage of days with RLS symptom | Standard Deviation 40.9 |
| SPM 962 4.5 | Incidence of RLS Symptoms | Baseline | 85.4 percentage of days with RLS symptom | Standard Deviation 20.5 |
| SPM 962 4.5 | Incidence of RLS Symptoms | Week 13 | 35.8 percentage of days with RLS symptom | Standard Deviation 38.6 |
| SPM 962 6.75 | Incidence of RLS Symptoms | Baseline | 83.2 percentage of days with RLS symptom | Standard Deviation 22.2 |
| SPM 962 6.75 | Incidence of RLS Symptoms | Week 13 | 36.8 percentage of days with RLS symptom | Standard Deviation 38.8 |
Secondary
Incidence of RLS Symptoms in the Evening and Night
Incidence rate of RLS symptoms is calculated as the number of days with RLS symptoms / the number of days of evaluation \* 100%.
Time frame: Baseline, the end of dose-titration/dose-maintenance period (week 13)
Population: FAS, LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Incidence of RLS Symptoms in the Evening and Night | Baseline | 80.6 percentage of days/week with symptoms | Standard Deviation 24.2 |
| Placebo | Incidence of RLS Symptoms in the Evening and Night | Week 13 | 45.4 percentage of days/week with symptoms | Standard Deviation 41 |
| SPM 962 4.5 | Incidence of RLS Symptoms in the Evening and Night | Baseline | 83.3 percentage of days/week with symptoms | Standard Deviation 20.8 |
| SPM 962 4.5 | Incidence of RLS Symptoms in the Evening and Night | Week 13 | 34.6 percentage of days/week with symptoms | Standard Deviation 38.2 |
| SPM 962 6.75 | Incidence of RLS Symptoms in the Evening and Night | Baseline | 79.5 percentage of days/week with symptoms | Standard Deviation 24.2 |
| SPM 962 6.75 | Incidence of RLS Symptoms in the Evening and Night | Week 13 | 31.8 percentage of days/week with symptoms | Standard Deviation 37.7 |
Secondary
Nocturnal Awakenings Due to RLS Symptoms in a Week
Nocturnal awakening rate is calculated as the number of days with nocturnal awakenings / the number of days of evaluation \* 100%.
Time frame: Baseline, the end of dose-titration/dose-maintenance period (week 13)
Population: FAS, LOCF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Nocturnal Awakenings Due to RLS Symptoms in a Week | Baseline | 33.5 percentage of days/week with awakening | Standard Deviation 35.9 |
| Placebo | Nocturnal Awakenings Due to RLS Symptoms in a Week | Week 13 | 15.6 percentage of days/week with awakening | Standard Deviation 31.7 |
| SPM 962 4.5 | Nocturnal Awakenings Due to RLS Symptoms in a Week | Baseline | 22.6 percentage of days/week with awakening | Standard Deviation 31.3 |
| SPM 962 4.5 | Nocturnal Awakenings Due to RLS Symptoms in a Week | Week 13 | 7.7 percentage of days/week with awakening | Standard Deviation 20.5 |
| SPM 962 6.75 | Nocturnal Awakenings Due to RLS Symptoms in a Week | Baseline | 28.3 percentage of days/week with awakening | Standard Deviation 34.3 |
| SPM 962 6.75 | Nocturnal Awakenings Due to RLS Symptoms in a Week | Week 13 | 7.5 percentage of days/week with awakening | Standard Deviation 19.5 |
Secondary
Patient Global Impression (PGI) Improvement
PGI improvement is a patient-reported scale for assessing how much the patient's illness has improved or worsened from baseline. The scale scoring criteria are 1: very much better, 2: much better, 3: a little better, 4: no change, 5: a little worse, 6: much worse, 7: very much worse.
Time frame: Baseline, the end of dose-titration/dose-maintenance period (week 13)
Population: FAS, LOCF
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Patient Global Impression (PGI) Improvement | Subjects with much improved | 23.2 Percentage of Participants |
| Placebo | Patient Global Impression (PGI) Improvement | Subjects with very much improved | 38.9 Percentage of Participants |
| SPM 962 4.5 | Patient Global Impression (PGI) Improvement | Subjects with much improved | 24.7 Percentage of Participants |
| SPM 962 4.5 | Patient Global Impression (PGI) Improvement | Subjects with very much improved | 48.4 Percentage of Participants |
| SPM 962 6.75 | Patient Global Impression (PGI) Improvement | Subjects with much improved | 30.1 Percentage of Participants |
| SPM 962 6.75 | Patient Global Impression (PGI) Improvement | Subjects with very much improved | 50.5 Percentage of Participants |
Secondary
The Pittsburgh Sleep Quality Index (PSQI)
Change of PSQI from baseline to the end of dose-titration/dose-maintenance period. 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.
Time frame: Baseline, the end of dose-titration/dose-maintenance period (week 13)
Population: FAS, LOCF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | The Pittsburgh Sleep Quality Index (PSQI) | -2.5 Scores on a scale | Standard Deviation 2.4 |
| SPM 962 4.5 | The Pittsburgh Sleep Quality Index (PSQI) | -3.1 Scores on a scale | Standard Deviation 3.2 |
| SPM 962 6.75 | The Pittsburgh Sleep Quality Index (PSQI) | -3.2 Scores on a scale | Standard Deviation 3.3 |