The Effects Of Ropinirole On Mood Or Mild Depression In Patients With Moderate To Severe Restless Legs Syndrome

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00357097
• Collaborator: (none)
• Enrollment: 240
• Locations: 50
• Duration (Months): 18
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Restless Legs Syndrome; Moderate to Severe Idiopathic Restless Legs Syndrome (RLS)	Drug: Ropinirole	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter 3:1-randomized Placebo-controlled Double-blind Phase IIIb Study on the Effects of Ropinirole on Mood/(Subclinical) Depression in the Therapy of Patients With Moderate to Severe Idiopathic RLS in Germany
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Dec 1, 2007
• Actual Study Completion Date: Dec 1, 2007

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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).

3. 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).

4. 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.

5. 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.

6. 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.

7. 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).

8. 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.

9. 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.

10. 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.

11. 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).

12. 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.

13. 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

14. 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

15. 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.

16. 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.

17. 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.

18. 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.

19. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Ellwangen	Baden-Wuerttemberg	Germany	73479
2	GSK Investigational Site	Freiburg	Baden-Wuerttemberg	Germany	79104
3	GSK Investigational Site	Ostfildern	Baden-Wuerttemberg	Germany	73760
4	GSK Investigational Site	Ulm	Baden-Wuerttemberg	Germany	89073
5	GSK Investigational Site	Ulm	Baden-Wuerttemberg	Germany	89081
6	GSK Investigational Site	Muenchen	Bayern	Germany	80331
7	GSK Investigational Site	Nuernberg	Bayern	Germany	90403
8	GSK Investigational Site	Regensburg	Bayern	Germany	93053
9	GSK Investigational Site	Unterhaching	Bayern	Germany	82008
10	GSK Investigational Site	Wuerzburg	Bayern	Germany	97070
11	GSK Investigational Site	Bad Saarow	Brandenburg	Germany	15526
12	GSK Investigational Site	Bad Homburg	Hessen	Germany	61348
13	GSK Investigational Site	Butzbach	Hessen	Germany	35510
14	GSK Investigational Site	Herborn	Hessen	Germany	35745
15	GSK Investigational Site	Kassel	Hessen	Germany	34128
16	GSK Investigational Site	Anklam	Mecklenburg-Vorpommern	Germany	17389
17	GSK Investigational Site	Schwerin	Mecklenburg-Vorpommern	Germany	19053
18	GSK Investigational Site	Wismar	Mecklenburg-Vorpommern	Germany	23966
19	GSK Investigational Site	Achim	Niedersachsen	Germany	28832
20	GSK Investigational Site	Goettingen	Niedersachsen	Germany	37073
21	GSK Investigational Site	Goettingen	Niedersachsen	Germany	37075
22	GSK Investigational Site	Hildesheim	Niedersachsen	Germany	31134
23	GSK Investigational Site	Wolfsburg	Niedersachsen	Germany	38440
24	GSK Investigational Site	Bielefeld	Nordrhein-Westfalen	Germany	33647
25	GSK Investigational Site	Bochum	Nordrhein-Westfalen	Germany	44787
26	GSK Investigational Site	Bochum	Nordrhein-Westfalen	Germany	44791
27	GSK Investigational Site	Bochum	Nordrhein-Westfalen	Germany	44805
28	GSK Investigational Site	Bochum	Nordrhein-Westfalen	Germany	44809
29	GSK Investigational Site	Bochum	Nordrhein-Westfalen	Germany	44892
30	GSK Investigational Site	Dueren	Nordrhein-Westfalen	Germany	52349
31	GSK Investigational Site	Duesseldorf	Nordrhein-Westfalen	Germany	40212
32	GSK Investigational Site	Gelsenkirchen	Nordrhein-Westfalen	Germany	45879
33	GSK Investigational Site	Guetersloh	Nordrhein-Westfalen	Germany	33330
34	GSK Investigational Site	Hattingen	Nordrhein-Westfalen	Germany	45525
35	GSK Investigational Site	Juelich	Nordrhein-Westfalen	Germany	52428
36	GSK Investigational Site	Limburgerhof	Rheinland-Pfalz	Germany	67117
37	GSK Investigational Site	Halle	Sachsen-Anhalt	Germany	06118
38	GSK Investigational Site	Koethen	Sachsen-Anhalt	Germany	06366
39	GSK Investigational Site	Dresden	Sachsen	Germany	01307
40	GSK Investigational Site	Oldenburg	Schleswig-Holstein	Germany	26122
41	GSK Investigational Site	Gera	Thueringen	Germany	07551
42	GSK Investigational Site	Jena	Thueringen	Germany	07743
43	GSK Investigational Site	Berlin		Germany	10117
44	GSK Investigational Site	Berlin		Germany	10625
45	GSK Investigational Site	Berlin		Germany	10629
46	GSK Investigational Site	Berlin		Germany	10787
47	GSK Investigational Site	Berlin		Germany	10969
48	GSK Investigational Site	Berlin		Germany	12167
49	GSK Investigational Site	Berlin		Germany	13053
50	GSK Investigational Site	Berlin		Germany	13156

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00357097
• Other Study ID Numbers: RRL106721
• First Posted: Jul 27, 2006
• Last Update Posted: Jun 7, 2012
• Last Verified: May 1, 2011

• Keywords provided by GlaxoSmithKline: randomised; ropinirole; depression; RLS; placebo; mood; double-blind; restless legs syndrome; germany
• Additional relevant MeSH terms: Psychomotor Agitation; Restless Legs Syndrome; Syndrome; Depression; Ropinirole

Study Results

Participant Flow

Arm/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Period Title: Overall Study
STARTED	199	67
COMPLETED	145	38
NOT COMPLETED	54	29

Baseline Characteristics

Arm/Group Title	Ropinirole	Placebo	Total
Arm/Group Description	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.	Subjects who took no investigational product.	Total of all reporting groups
Overall Participants	198	67	265
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	58.2 (11.4)	59.5 (11.3)	58.5 (11.4)
Sex: Female, Male (Count of Participants)
Female	144 72.7%	45 67.2%	189.0 71.3%
Male	54 27.3%	22 32.8%	76.0 28.7%

Outcome Measures

1. Primary Outcome

Title	Average Change of the MADRS (Montgomery-Asberg Depression Rating Scale) Total Score From Baseline to Final Visit After 12 Weeks of Treatment
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	171	60
Mean (Standard Deviation) [Score on a Scale]	-10.1 (7.3)	-6.5 (7.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ropinirole, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.6
	Confidence Interval	() 95%; -5.6 to -1.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference = Ropinirole minus Placebo. Used adjusted change from baseline.

2. Secondary Outcome

Title	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)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	91	29
Mean (Standard Deviation) [Score on a Scale]	-12.5 (8.0)	-8.8 (9.2)

3. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	166	55
Mean (Standard Deviation) [Score on a Scale]	-8.2 (5.5)	-5.5 (6.4)

4. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	93	33
Mean (Standard Deviation) [Score on a Scale]	-9.6 (5.9)	-7.2 (6.6)

5. Secondary Outcome

Title	Average Change of the Beck Depression Inventory (BDI) Total Score From Baseline to Final Visit After 12 Weeks of Treatment
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	169	60
Mean (Standard Deviation) [Score on a Scale]	-8.6 (7.0)	-6.5 (7.8)

6. Secondary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	75	28
Mean (Standard Deviation) [Score on a Scale]	-10.9 (7.9)	-9.9 (9.0)

7. Secondary Outcome

Title	Percentage of Participants With at Least Moderate Depression (MADRS Score >= 18) at Baseline and in Week 12
Description	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

Outcome Measure Data

Analysis Population Description

Modified Intent to Treat (mITT): All treated patients with MADRS score at baseline and post baseline (i.e., at week 12).

Arm/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	171	60
Number [Percentage of Participants]	11.7 5.9%	23.3 34.8%

8. Secondary Outcome

Title	Percentage of Participants With at Least Moderate Depression (HAM-D >= 15) at Baseline and in Week 12
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	168	56
Number [Percentage of Participants]	10.7 5.4%	26.8 40%

9. Secondary Outcome

Title	Percentage of Participants ("Responder") With a Decrease of MADRS Total Score of at Least 6 Points After 12 Weeks Compared to Baseline
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	171	60
Number [Percentage of Participants]	74.9 37.8%	48.3 72.1%

10. Secondary Outcome

Title	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)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	91	29
Number [Percentage of Participants]	80.2 40.5%	58.6 87.5%

11. Secondary Outcome

Title	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)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	93	34
Mean (Standard Deviation) [Score on a Scale]	-11.6 (7.7)	-7.6 (8.1)

12. Secondary Outcome

Title	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)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	90	31
Mean (Standard Deviation) [Score on a Scale]	-9.2 (5.6)	-6.5 (7.0)

13. Secondary Outcome

Title	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)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	91	34
Mean (Standard Deviation) [Score on a Scale]	-10.4 (6.8)	-7.2 (8.2)

14. Secondary Outcome

Title	Change in Average International Restless Legs Scale for Severity (IRLS) Scores in All Participants From Baseline to After 1, 4, and 12 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT): All patients of the safety population with any psychometric data at baseline (within a single questionnaire)

Arm/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	171	60
Change from Baseline after 1 Week	-7.7 (8.0)	-4.1 (5.4)
Change from Baseline after 4 Weeks	-14.0 (9.2)	-8.6 (8.5)
Change from Baseline after 12 Weeks	-14.6 (9.2)	-10.2 (10.6)

15. Secondary Outcome

Title	Percentage of Participants With a Decrease of International Restless Legs Scale (IRLS) Scores of at Least 6 Points After 1, 4 and 12 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT): All patients of the safety population with any psychometric data at baseline (within a single questionnaire)

Arm/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	171	60
1 Week	52.6 26.6%	28.3 42.2%
4 Weeks	80.7 40.8%	58.3 87%
12 Weeks	84.8 42.8%	61.7 92.1%

16. Secondary Outcome

Title	Percentage of Participants With "Much Improved" or "Very Much Improved" on the Clinical Global Impression-Global Improvement Scale After 1, 4 and 12 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT): All patients of the safety population with any psychometric data at baseline (within a single questionnaire)

Arm/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	171	60
Week 1	35.1 17.7%	15.0 22.4%
Week 4	66.7 33.7%	40.0 59.7%
Week 12	64.3 32.5%	46.7 69.7%

17. Secondary Outcome

Title	Change From Average Baseline Score of Subscale of "Somnolence" in the Medical Outcomes Study Sleep Scale (MOS-SS) to Final Visit After 12 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT): All patients of the safety population with any psychometric data at baseline (within a single questionnaire)

Arm/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	171	59
Mean (Standard Deviation) [Score on a Scale]	-12.5 (19.4)	-10.2 (19.9)

18. Secondary Outcome

Title	Change From Average Baseline Scores of Subscale "Sleep Disturbance" of the Medical Outcomes Study Sleep Scale (MOS-SS) to Final Visit After 12 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT): All patients of the safety population with any psychometric data at baseline (within a single questionnaire)

Arm/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	167	59
Mean (Standard Deviation) [Score on a Scale]	-30.5 (24.5)	-15.8 (27.6)

19. Secondary Outcome

Title	Change From Average Baseline Scores of Subscale "Sleep Adequacy" of the Medical Outcomes Study Sleep Scale (MOS-SS)to Final Visit After 12 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT): All patients of the safety population with any psychometric data at baseline (within a single questionnaire)

Arm/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	170	59
Mean (Standard Deviation) [Score on a Scale]	34.0 (30.6)	15.6 (36.2)

20. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Intent to Treat (ITT): All patients of the safety population with any psychometric data at baseline (within a single questionnaire)

Arm/Group Title	Ropinirole	Placebo
Arm/Group Description	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.	Subjects who took no investigational product.
Measure Participants	170	59
Mean (Standard Deviation) [Score on a Scale]	1.3 (1.3)	0.5 (1.4)

Adverse Events

Arm/Group Title	Ropinirole		Placebo
Arm/Group Description	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.		Subjects who took no investigational product.
All Cause Mortality
	Ropinirole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ropinirole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/ (NaN)		0/ (NaN)
Gastrointestinal disorders
Nausea	1/197 (0.5%)		0/67 (0%)
Vomiting	1/197 (0.5%)		0/67 (0%)
Infections and infestations
Bronchitis	1/197 (0.5%)	1	0/67 (0%)	0
Pregnancy, puerperium and perinatal conditions
Abortion Missed	1/197 (0.5%)	1	0/67 (0%)	0
Respiratory, thoracic and mediastinal disorders
Back Pain	1/197 (0.5%)		0/67 (0%)
Pulmonary Embolism	1/197 (0.5%)		0/67 (0%)
Other (Not Including Serious) Adverse Events
	Ropinirole		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	134/ (NaN)		20/ (NaN)
Gastrointestinal disorders
Nausea	64/197 (32.5%)		5/67 (7.5%)
Vomiting	14/197 (7.1%)		0/67 (0%)
General disorders
Fatigue	25/197 (12.7%)		4/67 (6%)
Nervous system disorders
Dizziness	17/197 (8.6%)		2/67 (3%)
Headache	39/197 (19.8%)		9/67 (13.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centres of a multi-centre trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.