Moderate to Severe Idiopathic Restless Legs Syndrome (RLS), Restless Legs Syndrome
Conditions
Keywords
randomised, ropinirole, depression, RLS, placebo, mood, double-blind, restless legs syndrome, germany
Brief summary
Ropinirole has shown to improve mood in depressed patients as well as to improve the symptoms of Restless Legs Syndrome. Up to 40% of RLS patients suffer from mild depression, therefore it would be important for decisions no therapy to know whether a drug could improve both depressive and RLS symptoms.
Interventions
DRUGRopinirole
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* diagnosis of idiopathic Restless Legs Syndrome, confirmed by a score of at least 11 on the RLS Diagnostic Index * certain severity of symptoms (at least score of 15 on the International Restless Legs Score (IRLS) * Have had RLS symptoms for at least 15 nights in the last four weeks. * \< 6 hours of sleep in nights with RLS symptoms * MADRS (depression rating scale) score of at least 12 (= borderline to depression) at baseline
Exclusion criteria
* any other sleep disorder that might interfere with the RLS symptoms or sleep (e.g. sleep apnea disorder, narcolepsy) * Secondary RLS due to diagnosis of renal insufficiency, polyneuropathy, pregnancy (see below), iron deficiency anemia * Any significant psychiatric disorders (e.g. schizophrenia, bipolar disorder); depression which by judgement of the investigator is caused by RLS, is not an exclusion criterion. * Current or past suicidality * medication known to trigger/aggravate/ cause or interfere with RLS symptoms (e.g. most antidepressants, lithium, neuroleptics, opioids, carbidopa, clonidine, antihistamines, anticonvulsants etc.). * daytime RLS symptoms which require treatment (daytime: 10 a.m. until 6 p.m.). * concomitant movement disorders (e.g. Parkinson's Disease, dyskinesia, dystonia). * medical conditions with symptoms which could affect assessments of efficacy (e.g. diabetes, rheumatoid arthritis, fibromyalgia syndrome, cancer etc.). * Subjects taking any medication known to induce drowsiness or to affect sleep. * Subjects who are pregnant, lactating or of childbearing potential. Women of childbearing potential must use adequate contraception * clinically significant or unstable medical conditions (e.g. severe heart disease, severe liver or kidney disease etc.). * pain syndromes, caused by other disorders than RLS * excessive caffeine intake * diastolic blood pressure \>110mmHg or \<50mmHg or systolic blood pressure \>180mmHg or \<90mmHg at baseline. * Withdrawal, introduction, or change in dose of hormone replacement therapy (HRT) or the oral contraceptive pill (OCP) and/or certain drugs which are known to interact with ropinirole (e.g. ciprofloxacin, cimetidine, tobacco, omeprazole).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Change of the MADRS (Montgomery-Asberg Depression Rating Scale) Total Score From Baseline to Final Visit After 12 Weeks of Treatment | Baseline and Week 12 | Montgomery-Asberg Depression Rating Scale (MADRS)is a 10 item questionaire preformed during a clinical interview asking broad to detailed questions about symptoms which allows a precise rating of severity of symptoms of the past week. Questions are scored 0-6. Total Score 0-60, the higher the score indicates the most severely depressed patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Change of the HAM-D (Hamilton Depression Rating Scale, 17-item-Version) Total Score From Baseline to Final Visit After 12 Weeks of Treatment | Baseline and Week 12 | The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAMD score range from 0 (not ill) to 54 (severely ill). |
| Average Change of the HAM-D Total Score From Baseline to Final Visit After 12 Weeks of Treatment in Participants With Signs of an at Least Moderate Depression (HAM-D Score >= 15) at Baseline | Baseline and Week 12 | The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAMD score range from 0 (not ill) to 54(severely ill). |
| Average Change of the Beck Depression Inventory (BDI) Total Score From Baseline to Final Visit After 12 Weeks of Treatment | Baseline and Week 12 | Becks Depression Inventory (BDI) is a 21 item self inventory evaluating symptoms of depression, cognition, and physical symptoms of fatigue, weight loss, and lack of interest in sex. The Higher the score represents most severely depressed participants. Score range for each items is 0-3 and Total score 0-63. |
| Average Change of the Beck Depression Inventory (BDI) Total Score From Baseline to Final Visit After 12 Weeks of Treatment in Participants With Signs of an at Least Mild-moderate Depression (BDI >= 21) at Baseline | Baseline and Week 12 | Becks Depression Inventory (BDI) is a 21 item self inventory evaluating symptoms of depression, cognition, and physical symptoms of fatigue, weight loss, and lack of interest in sex. The Higher the score represents most severely depressed participants. Score range for each items is 0-3 and total score 0-63. |
| Percentage of Participants With at Least Moderate Depression (MADRS Score >= 18) at Baseline and in Week 12 | Baseline and Week 12 | Montgomery-Asberg Depression Rating Scale (MADRS)is a 10 item questionaire preformed during a clinical interview asking broad to detailed questions about symptoms which allows a precise rating of severity of symptoms of the past week. Questions are scored 0-6. Total Score 0-60, the higher the score indicates the most severely depressed patients. |
| Percentage of Participants With at Least Moderate Depression (HAM-D >= 15) at Baseline and in Week 12 | Baseline and Week 12 | The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAMD score range from 0 (not ill) to 54 (severely ill). |
| Percentage of Participants (Responder) With a Decrease of MADRS Total Score of at Least 6 Points After 12 Weeks Compared to Baseline | Baseline and Week 12 | Montgomery-Asberg Depression Rating Scale (MADRS)is a 10 item questionaire preformed during a clinical interview asking broad to detailed questions about symptoms which allows a precise rating of severity of symptoms of the past week. Questions are scored 0-6. Total Score 0-60, the higher the score indicates the most severely depressed patients. |
| Percentage of Participants (Responder) With a Decrease of MADRS Total Score of at Least 6 Points After 12 Weeks Compared to Baseline in Subjects With Signs of at Least Moderate Depression at Baseline (MADRS Score >= 18) | Baseline and Week 12 | Montgomery-Asberg Depression Rating Scale (MADRS)is a 10 item questionaire preformed during a clinical interview asking broad to detailed questions about symptoms which allows a precise rating of severity of symptoms of the past week. Questions are scored 0-6. Total Score 0-60, the higher the score indicates the most severely depressed patients. |
| Change in Average MADRS Score From Baseline to Final Visit (Week 12) in Participants With Major Depressive Episodes (Diagnosed by MINI Interview Modules A, B and C / DSM Criteria) | Baseline and Week 12 | Montgomery-Asberg Depression Rating Scale (MADRS)is a 10 item questionaire preformed during a clinical interview asking broad to detailed questions about symptoms which allows a precise rating of severity of symptoms of the past week. Questions are scored 0-6. Total Score 0-60, the higher the score indicates the most severely depressed patients. |
| Average Change of the MADRS (Montgomery-Asberg Depression Rating Scale) Total Score From Baseline to Final Visit After 12 Weeks of Treatment in Participants With Signs of at Least Moderate Depression (MADRS Score: >=18) | Baseline and Week 12 | Montgomery-Asberg Depression Rating Scale (MADRS)is a 10 item questionaire preformed during a clinical interview asking broad to detailed questions about symptoms which allows a precise rating of severity of symptoms of the past week. Questions are scored 0-6. Total Score 0-60, the higher the score indicates the most severely depressed patients. |
| Change in Average BDI Score From Baseline to Final Visit (Week 12) in Participants With Major Depressive Episodes (Diagnosed by MINI Interview Modules A, B and C / DSM Criteria) | Baseline and Week 12 | Becks Depression Inventory (BDI) is a 21 item self inventory evaluating symptoms of depression, cognition, and physical symptoms of fatigue, weight loss, and lack of interest in sex. The Higher the score represents most severely depressed participants. Score range for each items is 0-3 and Total score 0-63. |
| Change in Average International Restless Legs Scale for Severity (IRLS) Scores in All Participants From Baseline to After 1, 4, and 12 Weeks | Baseline, Week 1, Week 4, Week 12 | International Restless Legs Scale for Severity (IRLS)is a series of 10 questions which rate severity from 0-4 points for various questions and total score ranks: Very severe=31-40 points, Severe=21-30 points, Moderate=11-20 points, and Mild=1-10 points, None=0 points |
| Percentage of Participants With a Decrease of International Restless Legs Scale (IRLS) Scores of at Least 6 Points After 1, 4 and 12 Weeks | Week 1, Week 4, Week 12 | International Restless Legs Scale for Severity (IRLS)is a series of 10 questions which rate severity from 0-4 points for various questions and total score ranks: Very severe=31-40 points, Severe=21-30 points, Moderate=11-20 points, and Mild=1-10 points, None=0 points |
| Percentage of Participants With Much Improved or Very Much Improved on the Clinical Global Impression-Global Improvement Scale After 1, 4 and 12 Weeks | Week 1, Week 4, Week 12 | The CGI-I assesses the investigator's impression of the patient's current illness. The time span is the week before the rating and the score range: 1-very much improved, 2-much improved, 3-minimally improved, 4-no change, 5- minimally worse, 6-much worse, to 7-very much worse. |
| Change From Average Baseline Score of Subscale of Somnolence in the Medical Outcomes Study Sleep Scale (MOS-SS) to Final Visit After 12 Weeks | Baseline and after Week 12 | Medical Outcome Study Sleep Scale (MOS-SS)-is a 12 item questionaire assessing sleep disturbance, sleep adequacy, somnolence, quantity of sleep, snoring, and awakening short of breath or with a headache. 10 question score from 1-6, 1 question scores 1-5 and 1 question asks average number of hours sleep each night. |
| Change From Average Baseline Scores of Subscale Sleep Disturbance of the Medical Outcomes Study Sleep Scale (MOS-SS) to Final Visit After 12 Weeks | Baseline and after Week 12 | Medical Outcome Study Sleep Scale (MOS-SS)-is a 12 item questionaire assessing sleep disturbance, sleep adequacy, somnolence, quantity of sleep, snoring, and awakening short of breath or with a headache. 10 question score from 1-6, 1 question scores 1-5 and 1 question asks average number of hours sleep each night. |
| Change From Average Baseline Scores of Subscale Sleep Adequacy of the Medical Outcomes Study Sleep Scale (MOS-SS)to Final Visit After 12 Weeks | Baseline and after Week 12 | Medical Outcome Study Sleep Scale (MOS-SS)-is a 12 item questionaire assessing sleep disturbance, sleep adequacy, somnolence, quantity of sleep, snoring, and awakening short of breath or with a headache. 10 question score from 1-6, 1 question scores 1-5 and 1 question asks average number of hours sleep each night. |
| Change From Average Baseline Scores of Subscale Sleep Quantity (Hours) of the Medical Outcomes Study Sleep Scale (MOS-SS) to Final Visit After 12 Weeks | Baseline and after Week 12 | — |
| Change in Average HAM-D Score From Baseline to Final Visit (Week 12) in Participants With Major Depressive Episodes (Diagnosed by MINI Interview Modules A, B and C / DSM Criteria) | Baseline and Week 12 | The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAMD score range from 0 (not ill) to 54 (severely ill). |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ropinirole Subjects who were treated on day 1-2 with 0.25 mg/day of ropinirole and on days 3-7 0.5 mg for 12 weeks if tolerated. After two weeks, dose could be increased weekly by 0.5mg a day up to 4 mg maximum dose. | 198 |
| Placebo Subjects who took no investigational product. | 67 |
| Total | 265 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 34 | 6 |
| Overall Study | Did not meet inclusion criteria | 5 | 3 |
| Overall Study | Increase of RLS Symptoms | 0 | 1 |
| Overall Study | Lack of Efficacy | 2 | 8 |
| Overall Study | Met Exclusion Criteria | 3 | 1 |
| Overall Study | Non-compliance | 1 | 2 |
| Overall Study | Other | 1 | 1 |
| Overall Study | Withdrawal by Subject | 8 | 7 |
Baseline characteristics
| Characteristic | Ropinirole | Placebo | Total |
|---|---|---|---|
| Age Continuous | 58.2 Years STANDARD_DEVIATION 11.4 | 59.5 Years STANDARD_DEVIATION 11.3 | 58.5 Years STANDARD_DEVIATION 11.4 |
| Sex: Female, Male Female | 144 Participants | 45 Participants | 189.0 Participants |
| Sex: Female, Male Male | 54 Participants | 22 Participants | 76.0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 134 / — | 20 / — |
| serious Total, serious adverse events | 4 / — | 0 / — |
Outcome results
Primary
Average Change of the MADRS (Montgomery-Asberg Depression Rating Scale) Total Score From Baseline to Final Visit After 12 Weeks of Treatment
Montgomery-Asberg Depression Rating Scale (MADRS)is a 10 item questionaire preformed during a clinical interview asking broad to detailed questions about symptoms which allows a precise rating of severity of symptoms of the past week. Questions are scored 0-6. Total Score 0-60, the higher the score indicates the most severely depressed patients.
Time frame: Baseline and Week 12
Population: Modified Intent to Treat (mITT): All treated patients with MADRS score at baseline and post baseline (i.e., at visit 4 and/or 5). The High/Low scores for this population were 32/11.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ropinirole | Average Change of the MADRS (Montgomery-Asberg Depression Rating Scale) Total Score From Baseline to Final Visit After 12 Weeks of Treatment | -10.1 Score on a Scale | Standard Deviation 7.3 |
| Placebo | Average Change of the MADRS (Montgomery-Asberg Depression Rating Scale) Total Score From Baseline to Final Visit After 12 Weeks of Treatment | -6.5 Score on a Scale | Standard Deviation 7.6 |
p-value: <0.00195% CI: [-5.6, -1.6]ANCOVA
Secondary
Average Change of the Beck Depression Inventory (BDI) Total Score From Baseline to Final Visit After 12 Weeks of Treatment
Becks Depression Inventory (BDI) is a 21 item self inventory evaluating symptoms of depression, cognition, and physical symptoms of fatigue, weight loss, and lack of interest in sex. The Higher the score represents most severely depressed participants. Score range for each items is 0-3 and Total score 0-63.
Time frame: Baseline and Week 12
Population: Modified Intent to Treat (mITT): All treated patients with MADRS score at baseline and post baseline (i.e., at visit 4 and/or 5). High/Low BDI scores for this population were 46/2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ropinirole | Average Change of the Beck Depression Inventory (BDI) Total Score From Baseline to Final Visit After 12 Weeks of Treatment | -8.6 Score on a Scale | Standard Deviation 7 |
| Placebo | Average Change of the Beck Depression Inventory (BDI) Total Score From Baseline to Final Visit After 12 Weeks of Treatment | -6.5 Score on a Scale | Standard Deviation 7.8 |
Secondary
Average Change of the Beck Depression Inventory (BDI) Total Score From Baseline to Final Visit After 12 Weeks of Treatment in Participants With Signs of an at Least Mild-moderate Depression (BDI >= 21) at Baseline
Becks Depression Inventory (BDI) is a 21 item self inventory evaluating symptoms of depression, cognition, and physical symptoms of fatigue, weight loss, and lack of interest in sex. The Higher the score represents most severely depressed participants. Score range for each items is 0-3 and total score 0-63.
Time frame: Baseline and Week 12
Population: Modified Intent to Treat (mITT): All treated patients with MADRS score at baseline and post baseline (i.e., at visit 4 and/or 5). Sub-population with BDI scores\>=21: Ropinirole 75 and Placebo 28. High/Low BDI scores for this population were 46/2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ropinirole | Average Change of the Beck Depression Inventory (BDI) Total Score From Baseline to Final Visit After 12 Weeks of Treatment in Participants With Signs of an at Least Mild-moderate Depression (BDI >= 21) at Baseline | -10.9 Score on a Scale | Standard Deviation 7.9 |
| Placebo | Average Change of the Beck Depression Inventory (BDI) Total Score From Baseline to Final Visit After 12 Weeks of Treatment in Participants With Signs of an at Least Mild-moderate Depression (BDI >= 21) at Baseline | -9.9 Score on a Scale | Standard Deviation 9 |
Secondary
Average Change of the HAM-D (Hamilton Depression Rating Scale, 17-item-Version) Total Score From Baseline to Final Visit After 12 Weeks of Treatment
The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAMD score range from 0 (not ill) to 54 (severely ill).
Time frame: Baseline and Week 12
Population: Modified Intent to Treat (mITT): All treated patients with MADRS score at baseline and post baseline (i.e., at visit 4 and/or 5). The High/Low HAM-D scores for this population were 27/5.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ropinirole | Average Change of the HAM-D (Hamilton Depression Rating Scale, 17-item-Version) Total Score From Baseline to Final Visit After 12 Weeks of Treatment | -8.2 Score on a Scale | Standard Deviation 5.5 |
| Placebo | Average Change of the HAM-D (Hamilton Depression Rating Scale, 17-item-Version) Total Score From Baseline to Final Visit After 12 Weeks of Treatment | -5.5 Score on a Scale | Standard Deviation 6.4 |
Secondary
Average Change of the HAM-D Total Score From Baseline to Final Visit After 12 Weeks of Treatment in Participants With Signs of an at Least Moderate Depression (HAM-D Score >= 15) at Baseline
The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAMD score range from 0 (not ill) to 54(severely ill).
Time frame: Baseline and Week 12
Population: Modified Intent to Treat (mITT): All treated patients with MADRS score at baseline and post baseline (i.e., at visit 4 and/or 5). Sub-population with HAM-D scores\>=15: Ropinirole 93 and Placebo 33
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ropinirole | Average Change of the HAM-D Total Score From Baseline to Final Visit After 12 Weeks of Treatment in Participants With Signs of an at Least Moderate Depression (HAM-D Score >= 15) at Baseline | -9.6 Score on a Scale | Standard Deviation 5.9 |
| Placebo | Average Change of the HAM-D Total Score From Baseline to Final Visit After 12 Weeks of Treatment in Participants With Signs of an at Least Moderate Depression (HAM-D Score >= 15) at Baseline | -7.2 Score on a Scale | Standard Deviation 6.6 |
Secondary
Average Change of the MADRS (Montgomery-Asberg Depression Rating Scale) Total Score From Baseline to Final Visit After 12 Weeks of Treatment in Participants With Signs of at Least Moderate Depression (MADRS Score: >=18)
Montgomery-Asberg Depression Rating Scale (MADRS)is a 10 item questionaire preformed during a clinical interview asking broad to detailed questions about symptoms which allows a precise rating of severity of symptoms of the past week. Questions are scored 0-6. Total Score 0-60, the higher the score indicates the most severely depressed patients.
Time frame: Baseline and Week 12
Population: Modified Intent to Treat (mITT): All treated patients with MADRS score at baseline and post baseline (i.e., at visit 4 and/or 5). Sub-population with MADRS scores\>=18: Ropinirole 91 and Placebo 29. The high/Low scores for the mITT population were 32/11.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ropinirole | Average Change of the MADRS (Montgomery-Asberg Depression Rating Scale) Total Score From Baseline to Final Visit After 12 Weeks of Treatment in Participants With Signs of at Least Moderate Depression (MADRS Score: >=18) | -12.5 Score on a Scale | Standard Deviation 8 |
| Placebo | Average Change of the MADRS (Montgomery-Asberg Depression Rating Scale) Total Score From Baseline to Final Visit After 12 Weeks of Treatment in Participants With Signs of at Least Moderate Depression (MADRS Score: >=18) | -8.8 Score on a Scale | Standard Deviation 9.2 |
Secondary
Change From Average Baseline Score of Subscale of Somnolence in the Medical Outcomes Study Sleep Scale (MOS-SS) to Final Visit After 12 Weeks
Medical Outcome Study Sleep Scale (MOS-SS)-is a 12 item questionaire assessing sleep disturbance, sleep adequacy, somnolence, quantity of sleep, snoring, and awakening short of breath or with a headache. 10 question score from 1-6, 1 question scores 1-5 and 1 question asks average number of hours sleep each night.
Time frame: Baseline and after Week 12
Population: Intent to Treat (ITT): All patients of the safety population with any psychometric data at baseline (within a single questionnaire)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ropinirole | Change From Average Baseline Score of Subscale of Somnolence in the Medical Outcomes Study Sleep Scale (MOS-SS) to Final Visit After 12 Weeks | -12.5 Score on a Scale | Standard Deviation 19.4 |
| Placebo | Change From Average Baseline Score of Subscale of Somnolence in the Medical Outcomes Study Sleep Scale (MOS-SS) to Final Visit After 12 Weeks | -10.2 Score on a Scale | Standard Deviation 19.9 |
Secondary
Change From Average Baseline Scores of Subscale Sleep Adequacy of the Medical Outcomes Study Sleep Scale (MOS-SS)to Final Visit After 12 Weeks
Medical Outcome Study Sleep Scale (MOS-SS)-is a 12 item questionaire assessing sleep disturbance, sleep adequacy, somnolence, quantity of sleep, snoring, and awakening short of breath or with a headache. 10 question score from 1-6, 1 question scores 1-5 and 1 question asks average number of hours sleep each night.
Time frame: Baseline and after Week 12
Population: Intent to Treat (ITT): All patients of the safety population with any psychometric data at baseline (within a single questionnaire)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ropinirole | Change From Average Baseline Scores of Subscale Sleep Adequacy of the Medical Outcomes Study Sleep Scale (MOS-SS)to Final Visit After 12 Weeks | 34.0 Score on a Scale | Standard Deviation 30.6 |
| Placebo | Change From Average Baseline Scores of Subscale Sleep Adequacy of the Medical Outcomes Study Sleep Scale (MOS-SS)to Final Visit After 12 Weeks | 15.6 Score on a Scale | Standard Deviation 36.2 |
Secondary
Change From Average Baseline Scores of Subscale Sleep Disturbance of the Medical Outcomes Study Sleep Scale (MOS-SS) to Final Visit After 12 Weeks
Medical Outcome Study Sleep Scale (MOS-SS)-is a 12 item questionaire assessing sleep disturbance, sleep adequacy, somnolence, quantity of sleep, snoring, and awakening short of breath or with a headache. 10 question score from 1-6, 1 question scores 1-5 and 1 question asks average number of hours sleep each night.
Time frame: Baseline and after Week 12
Population: Intent to Treat (ITT): All patients of the safety population with any psychometric data at baseline (within a single questionnaire)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ropinirole | Change From Average Baseline Scores of Subscale Sleep Disturbance of the Medical Outcomes Study Sleep Scale (MOS-SS) to Final Visit After 12 Weeks | -30.5 Score on a Scale | Standard Deviation 24.5 |
| Placebo | Change From Average Baseline Scores of Subscale Sleep Disturbance of the Medical Outcomes Study Sleep Scale (MOS-SS) to Final Visit After 12 Weeks | -15.8 Score on a Scale | Standard Deviation 27.6 |
Secondary
Change From Average Baseline Scores of Subscale Sleep Quantity (Hours) of the Medical Outcomes Study Sleep Scale (MOS-SS) to Final Visit After 12 Weeks
Time frame: Baseline and after Week 12
Population: Intent to Treat (ITT): All patients of the safety population with any psychometric data at baseline (within a single questionnaire)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ropinirole | Change From Average Baseline Scores of Subscale Sleep Quantity (Hours) of the Medical Outcomes Study Sleep Scale (MOS-SS) to Final Visit After 12 Weeks | 1.3 Score on a Scale | Standard Deviation 1.3 |
| Placebo | Change From Average Baseline Scores of Subscale Sleep Quantity (Hours) of the Medical Outcomes Study Sleep Scale (MOS-SS) to Final Visit After 12 Weeks | 0.5 Score on a Scale | Standard Deviation 1.4 |
Secondary
Change in Average BDI Score From Baseline to Final Visit (Week 12) in Participants With Major Depressive Episodes (Diagnosed by MINI Interview Modules A, B and C / DSM Criteria)
Becks Depression Inventory (BDI) is a 21 item self inventory evaluating symptoms of depression, cognition, and physical symptoms of fatigue, weight loss, and lack of interest in sex. The Higher the score represents most severely depressed participants. Score range for each items is 0-3 and Total score 0-63.
Time frame: Baseline and Week 12
Population: Modified Intent to Treat (mITT): All treated patients with MADRS score at baseline and post baseline (i.e., at visit 4 and/or 5). Sub-population diagnosed by MINI interview with Major Depressive Episodes: Ropinirole 91 and Placebo 34. High/Low BDI scores for this population were 46/2.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ropinirole | Change in Average BDI Score From Baseline to Final Visit (Week 12) in Participants With Major Depressive Episodes (Diagnosed by MINI Interview Modules A, B and C / DSM Criteria) | -10.4 Score on a Scale | Standard Deviation 6.8 |
| Placebo | Change in Average BDI Score From Baseline to Final Visit (Week 12) in Participants With Major Depressive Episodes (Diagnosed by MINI Interview Modules A, B and C / DSM Criteria) | -7.2 Score on a Scale | Standard Deviation 8.2 |
Secondary
Change in Average HAM-D Score From Baseline to Final Visit (Week 12) in Participants With Major Depressive Episodes (Diagnosed by MINI Interview Modules A, B and C / DSM Criteria)
The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAMD score range from 0 (not ill) to 54 (severely ill).
Time frame: Baseline and Week 12
Population: Modified Intent to Treat (mITT): All treated patients with MADRS score at baseline and post baseline (i.e., at visit 4 and/or 5). Sub-population diagnosed by MINI interview with Major Depressive Episodes: Ropinirole 90 and Placebo 31.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ropinirole | Change in Average HAM-D Score From Baseline to Final Visit (Week 12) in Participants With Major Depressive Episodes (Diagnosed by MINI Interview Modules A, B and C / DSM Criteria) | -9.2 Score on a Scale | Standard Deviation 5.6 |
| Placebo | Change in Average HAM-D Score From Baseline to Final Visit (Week 12) in Participants With Major Depressive Episodes (Diagnosed by MINI Interview Modules A, B and C / DSM Criteria) | -6.5 Score on a Scale | Standard Deviation 7 |
Secondary
Change in Average International Restless Legs Scale for Severity (IRLS) Scores in All Participants From Baseline to After 1, 4, and 12 Weeks
International Restless Legs Scale for Severity (IRLS)is a series of 10 questions which rate severity from 0-4 points for various questions and total score ranks: Very severe=31-40 points, Severe=21-30 points, Moderate=11-20 points, and Mild=1-10 points, None=0 points
Time frame: Baseline, Week 1, Week 4, Week 12
Population: Intent to Treat (ITT): All patients of the safety population with any psychometric data at baseline (within a single questionnaire)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ropinirole | Change in Average International Restless Legs Scale for Severity (IRLS) Scores in All Participants From Baseline to After 1, 4, and 12 Weeks | Change from Baseline after 12 Weeks | -14.6 Score on a Scale | Standard Deviation 9.2 |
| Ropinirole | Change in Average International Restless Legs Scale for Severity (IRLS) Scores in All Participants From Baseline to After 1, 4, and 12 Weeks | Change from Baseline after 1 Week | -7.7 Score on a Scale | Standard Deviation 8 |
| Ropinirole | Change in Average International Restless Legs Scale for Severity (IRLS) Scores in All Participants From Baseline to After 1, 4, and 12 Weeks | Change from Baseline after 4 Weeks | -14.0 Score on a Scale | Standard Deviation 9.2 |
| Placebo | Change in Average International Restless Legs Scale for Severity (IRLS) Scores in All Participants From Baseline to After 1, 4, and 12 Weeks | Change from Baseline after 4 Weeks | -8.6 Score on a Scale | Standard Deviation 8.5 |
| Placebo | Change in Average International Restless Legs Scale for Severity (IRLS) Scores in All Participants From Baseline to After 1, 4, and 12 Weeks | Change from Baseline after 12 Weeks | -10.2 Score on a Scale | Standard Deviation 10.6 |
| Placebo | Change in Average International Restless Legs Scale for Severity (IRLS) Scores in All Participants From Baseline to After 1, 4, and 12 Weeks | Change from Baseline after 1 Week | -4.1 Score on a Scale | Standard Deviation 5.4 |
Secondary
Change in Average MADRS Score From Baseline to Final Visit (Week 12) in Participants With Major Depressive Episodes (Diagnosed by MINI Interview Modules A, B and C / DSM Criteria)
Montgomery-Asberg Depression Rating Scale (MADRS)is a 10 item questionaire preformed during a clinical interview asking broad to detailed questions about symptoms which allows a precise rating of severity of symptoms of the past week. Questions are scored 0-6. Total Score 0-60, the higher the score indicates the most severely depressed patients.
Time frame: Baseline and Week 12
Population: Modified Intent to Treat (mITT): All treated patients with MADRS score at baseline and post baseline (i.e., at visit 4 and/or 5). Sub-population diagnosed by MINI interview with Major Depressive Episodes: Ropinirole 93 and Placebo 34
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ropinirole | Change in Average MADRS Score From Baseline to Final Visit (Week 12) in Participants With Major Depressive Episodes (Diagnosed by MINI Interview Modules A, B and C / DSM Criteria) | -11.6 Score on a Scale | Standard Deviation 7.7 |
| Placebo | Change in Average MADRS Score From Baseline to Final Visit (Week 12) in Participants With Major Depressive Episodes (Diagnosed by MINI Interview Modules A, B and C / DSM Criteria) | -7.6 Score on a Scale | Standard Deviation 8.1 |
Secondary
Percentage of Participants (Responder) With a Decrease of MADRS Total Score of at Least 6 Points After 12 Weeks Compared to Baseline
Montgomery-Asberg Depression Rating Scale (MADRS)is a 10 item questionaire preformed during a clinical interview asking broad to detailed questions about symptoms which allows a precise rating of severity of symptoms of the past week. Questions are scored 0-6. Total Score 0-60, the higher the score indicates the most severely depressed patients.
Time frame: Baseline and Week 12
Population: Modified Intent to Treat (mITT): All treated patients with MADRS score at baseline and post baseline (i.e., at visit 4 and/or 5).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ropinirole | Percentage of Participants (Responder) With a Decrease of MADRS Total Score of at Least 6 Points After 12 Weeks Compared to Baseline | 74.9 Percentage of Participants |
| Placebo | Percentage of Participants (Responder) With a Decrease of MADRS Total Score of at Least 6 Points After 12 Weeks Compared to Baseline | 48.3 Percentage of Participants |
Secondary
Percentage of Participants (Responder) With a Decrease of MADRS Total Score of at Least 6 Points After 12 Weeks Compared to Baseline in Subjects With Signs of at Least Moderate Depression at Baseline (MADRS Score >= 18)
Montgomery-Asberg Depression Rating Scale (MADRS)is a 10 item questionaire preformed during a clinical interview asking broad to detailed questions about symptoms which allows a precise rating of severity of symptoms of the past week. Questions are scored 0-6. Total Score 0-60, the higher the score indicates the most severely depressed patients.
Time frame: Baseline and Week 12
Population: Modified Intent to Treat (mITT): All treated patients with MADRS score at baseline and post baseline (i.e., at visit 4 and/or 5). Sub-population with MADRS scores\>=18: Ropinirole 91 and Placebo 29
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ropinirole | Percentage of Participants (Responder) With a Decrease of MADRS Total Score of at Least 6 Points After 12 Weeks Compared to Baseline in Subjects With Signs of at Least Moderate Depression at Baseline (MADRS Score >= 18) | 80.2 Percentage of Participants |
| Placebo | Percentage of Participants (Responder) With a Decrease of MADRS Total Score of at Least 6 Points After 12 Weeks Compared to Baseline in Subjects With Signs of at Least Moderate Depression at Baseline (MADRS Score >= 18) | 58.6 Percentage of Participants |
Secondary
Percentage of Participants With a Decrease of International Restless Legs Scale (IRLS) Scores of at Least 6 Points After 1, 4 and 12 Weeks
International Restless Legs Scale for Severity (IRLS)is a series of 10 questions which rate severity from 0-4 points for various questions and total score ranks: Very severe=31-40 points, Severe=21-30 points, Moderate=11-20 points, and Mild=1-10 points, None=0 points
Time frame: Week 1, Week 4, Week 12
Population: Intent to Treat (ITT): All patients of the safety population with any psychometric data at baseline (within a single questionnaire)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ropinirole | Percentage of Participants With a Decrease of International Restless Legs Scale (IRLS) Scores of at Least 6 Points After 1, 4 and 12 Weeks | 1 Week | 52.6 Percentage of Participants |
| Ropinirole | Percentage of Participants With a Decrease of International Restless Legs Scale (IRLS) Scores of at Least 6 Points After 1, 4 and 12 Weeks | 4 Weeks | 80.7 Percentage of Participants |
| Ropinirole | Percentage of Participants With a Decrease of International Restless Legs Scale (IRLS) Scores of at Least 6 Points After 1, 4 and 12 Weeks | 12 Weeks | 84.8 Percentage of Participants |
| Placebo | Percentage of Participants With a Decrease of International Restless Legs Scale (IRLS) Scores of at Least 6 Points After 1, 4 and 12 Weeks | 1 Week | 28.3 Percentage of Participants |
| Placebo | Percentage of Participants With a Decrease of International Restless Legs Scale (IRLS) Scores of at Least 6 Points After 1, 4 and 12 Weeks | 4 Weeks | 58.3 Percentage of Participants |
| Placebo | Percentage of Participants With a Decrease of International Restless Legs Scale (IRLS) Scores of at Least 6 Points After 1, 4 and 12 Weeks | 12 Weeks | 61.7 Percentage of Participants |
Secondary
Percentage of Participants With at Least Moderate Depression (HAM-D >= 15) at Baseline and in Week 12
The Hamilton Rating Scale for Depression contains 17 questions which detect change and measure illness severity. Individual items are rated on a scale of 0-4, 0-3, and 0-2 with total HAMD score range from 0 (not ill) to 54 (severely ill).
Time frame: Baseline and Week 12
Population: Modified Intent to Treat (mITT): All treated patients with MADRS score at baseline and post baseline (i.e., at visit 4 and/or 5). Sub-population with HAM-D scores\>=15.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ropinirole | Percentage of Participants With at Least Moderate Depression (HAM-D >= 15) at Baseline and in Week 12 | 10.7 Percentage of Participants |
| Placebo | Percentage of Participants With at Least Moderate Depression (HAM-D >= 15) at Baseline and in Week 12 | 26.8 Percentage of Participants |
Secondary
Percentage of Participants With at Least Moderate Depression (MADRS Score >= 18) at Baseline and in Week 12
Montgomery-Asberg Depression Rating Scale (MADRS)is a 10 item questionaire preformed during a clinical interview asking broad to detailed questions about symptoms which allows a precise rating of severity of symptoms of the past week. Questions are scored 0-6. Total Score 0-60, the higher the score indicates the most severely depressed patients.
Time frame: Baseline and Week 12
Population: Modified Intent to Treat (mITT): All treated patients with MADRS score at baseline and post baseline (i.e., at week 12).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ropinirole | Percentage of Participants With at Least Moderate Depression (MADRS Score >= 18) at Baseline and in Week 12 | 11.7 Percentage of Participants |
| Placebo | Percentage of Participants With at Least Moderate Depression (MADRS Score >= 18) at Baseline and in Week 12 | 23.3 Percentage of Participants |
Secondary
Percentage of Participants With Much Improved or Very Much Improved on the Clinical Global Impression-Global Improvement Scale After 1, 4 and 12 Weeks
The CGI-I assesses the investigator's impression of the patient's current illness. The time span is the week before the rating and the score range: 1-very much improved, 2-much improved, 3-minimally improved, 4-no change, 5- minimally worse, 6-much worse, to 7-very much worse.
Time frame: Week 1, Week 4, Week 12
Population: Intent to Treat (ITT): All patients of the safety population with any psychometric data at baseline (within a single questionnaire)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ropinirole | Percentage of Participants With Much Improved or Very Much Improved on the Clinical Global Impression-Global Improvement Scale After 1, 4 and 12 Weeks | Week 1 | 35.1 Percentage of Participants |
| Ropinirole | Percentage of Participants With Much Improved or Very Much Improved on the Clinical Global Impression-Global Improvement Scale After 1, 4 and 12 Weeks | Week 4 | 66.7 Percentage of Participants |
| Ropinirole | Percentage of Participants With Much Improved or Very Much Improved on the Clinical Global Impression-Global Improvement Scale After 1, 4 and 12 Weeks | Week 12 | 64.3 Percentage of Participants |
| Placebo | Percentage of Participants With Much Improved or Very Much Improved on the Clinical Global Impression-Global Improvement Scale After 1, 4 and 12 Weeks | Week 12 | 46.7 Percentage of Participants |
| Placebo | Percentage of Participants With Much Improved or Very Much Improved on the Clinical Global Impression-Global Improvement Scale After 1, 4 and 12 Weeks | Week 1 | 15.0 Percentage of Participants |
| Placebo | Percentage of Participants With Much Improved or Very Much Improved on the Clinical Global Impression-Global Improvement Scale After 1, 4 and 12 Weeks | Week 4 | 40.0 Percentage of Participants |