Clinical Evaluation of Ropinirole CR-RLS ( SK&F101468)Tablets in Restless Legs Syndrome

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00530790
• Collaborator: (none)
• Enrollment: 35
• Locations: 11
• Arm: 1
• Duration (Months): 5.3
• Patients Per Site: 3.2
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This study was designed to evaluate the safety, pharmacokinetic profile and efficacy in Restless Legs Syndrome patients.

Condition or Disease	Intervention/Treatment	Phase
Restless Legs Syndrome	Drug: ropinirole controlled release (CR)-RLS	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Clinical Evaluation of Ropinirole CR-RLS Tablets in Restless Legs Syndrome-Open-Label, Uncontrolled Study. Classification: Clinical Pharmacology, Exploratory
• Study Start Date: Aug 23, 2007
• Actual Primary Completion Date: Feb 1, 2008
• Actual Study Completion Date: Feb 1, 2008

Arms and Interventions

Arm

Intervention/Treatment

Experimental: ropinirole CR-RLS Subjects will orally take ropinirole CR-RLS tablet(s) once daily 1-2 hours before the onset of RLS symptoms at about the same time of the day. The time of taking ropinirole must be after 16:00.Adjustment of the Ropinirole CR-RLS tablets should be completed after the Week 1 visit up to the Week 10 visit. The dose will be increased at intervals of at least one week until sufficient efficacy is obtained (use "much improved" as a guide) without safety problem. Dose escalation will start at the initial dose 0.5 mg/day to 1 mg/day; after 1 mg/day, the dose will be increased by 1 mg/day to the maximum 6 mg/day.

Drug: ropinirole controlled release (CR)-RLS; White film-coated round-shaped tablet; Other Names: Ropinirole CR-RLS (SK&F101468)

Outcome Measures

Primary Outcome Measures

1. Drug Related Adverse Events-On-Therapy [Weeks 1 - 12 Treatment Period]

2. Haematology Clinical Lab Values Change From Baseline [Baseline - Week 13 (Follow-up)]

   Standard units of measure vary. Therefore, Mean Change is represented in Standard Units: Hematocrit = SI unit of GSK; Hemoglobin = G/L; Platelet count, White Blood Cell count = GI/L; Red Blood Cell count = TI/L. n = number of subjects evaluated. EW = Early Withdrawal.

3. Blood Chemistry Clinical Lab Values Change From Baseline [Baseline - Week 13 (Follow-up)]

   Mean Change in Standard Units of Measure: Albumin, Total Protein=G/L; Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Lactate Dehydrogenase, Creatine Phosphokinase, Gamma Glutamyl Transferase=IU/L; Total Bilirubin, Creatinine=UMOL/L; Blood Urea Nitrogen, Cholesterol, Chloride, Sodium, Potassium=MMOL/L; Prolactin=MCG/L

4. Urinalysis Clinical Lab Values [Baseline - Week 13 (Follow-up)]

   Dipstick test values: Neg Value, Trace, +1, +2, +3. No subjects tested higher than +3.

5. 12-Lead Electrocardiogram (ECG) Findings Transitions From Baseline [Baseline, Week 4, 8, 12, 13 (Follow-up)]

   Baseline Finding/Time Period Finding. Abbreviations: N = normal; A = abnormal; CS = clinically significant; NCS = not clinically significant. Options include N/N, N/ANCS, N/ACS, ANCS/N, ANCS/ANCS, ANCS/ACS, ACS/N, ACS/ANCS, and ACS/ACS.

6. Vital Signs and Body Weight Change From Baseline [Baseline to Week 12/EW]

   Units of Measure Vary: Weight = kg; Semi-supine and Standing Systolic and Diastolic BP = mmHg; Semi-supine and Standing Pulse Rate = bpm; EW = early withdrawal; Semi-supine = lying down; Orthostatic = lying, sitting, and standing.

Secondary Outcome Measures

1. Change From Baseline to Week 12 in International Restless Leg Syndrome (IRLS) Rating Scale Total Score [Baseline and after Week 12]

   The IRLS Scale assesses the severity of sensory and motor symptoms, sleep disturbance, daytime somnolence, and impact on activities of daily living and mood. The questionnaire scores various questions and totals them using the following scale: Very severe=31-40 points, Severe=21-30 points, Moderate=11-20 points, Mild=1-10 points, None=0 points.

2. Clinical Global Impression Scale - Severity of Illness (CGI-S) [Baseline - Final assessment point]

   The CGI-S scale measures the overall severity of illness on a 7 point scale. Normal = 1, Borderline = 2, Mildly = 3, Moderately = 4, Markedly = 5, Severely = 6, Extremely Severe = 7(no subjects scored a 7).

3. Clinical Global Impression Global Improvement (CGI-GI) [Baseline - Final assessment point]

   CGI-GI is a 7 point scale assessing Global Improvement. 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse (no patients scored a 5, 6, or 7).

4. Change From Baseline at Week 12/Early Withdrawal (EW) in Pittsburgh Sleep Quality Index (PSQI) Total Score [Baseline - Week 12/EW]

   The PSQI generates seven scores that correspond to different domains. Each component score ranges from 0 (no difficulty) to 3 (severe difficulty). The domain scores are totaled to produce a global score (range of 0-21). A PSQI global score > 5 is considered to be suggestive of significant sleep disturbance.

5. Change From Baseline to Week 12/EW in Pittsburgh Sleep Quality Index (PSQI) Total Score by Domains [Baseline - Week 12/EW]

   The PSQI generates seven scores that correspond to different domains. Each component score ranges from 0 (no difficulty) to 3 (severe difficulty). The domain scores are totaled to produce a global score (range of 0-21). A PSQI global score > 5 is considered to be suggestive of significant sleep disturbance.

6. Change From Baseline at Week 12/Early Withdrawal (EW) in Johns Hopkins Restless Leg Syndrome Quality of Life Questionnaire (RLSQOL) on the Overall Life Impact Score [Baseline and Week 12/EW]

   The RLSQOL scale consists of 18 items, 13 of which are scored on a 5-point scale. Ten of the items can be summed to the overall life impact score, which can be transformed to a 0-100 score. Mild = 84.48, Moderate = 62.93, or Severe = 37.47

7. Change From Baseline at Week 12/Early Withdrawal (EW) in Profile of Mood Status (POMS) [Baseline and Week 12/EW]

   The POMS Standard form contains 65 items (0-232). The respondent rates each item on a 5-point scale, ranging from "Not at all (0)" to "Extremely (4)." The assessment measures six identified mood factors: Tension-Anxiety Depression-Dejection Anger-Hostility Vigor-Activity Fatigue-Inertia Confusion-Bewilderment

8. Change From Baseline at Week 12/Early Withdrawal (EW) in Hospital Anxiety and Depression Scale (HADS) [Baseline - Week 12/EW]

   Self screening questionnaire that requires the first response to questions. Questionnaire consists of 14 questions, seven for anxiety "0-21" and seven for depression "0-21". Questions are answered on a four point scale from 0-3; Items 1, 3, 5, 6, 8, 10, 11, and 13 are reversed for summation.

9. Pharmacokinetic Analysis: Plasma Concentrations of SK&F101468, an Unchanged Form of Ropinirole. [Weeks 1-12]

   Plasma samples taken at 24 hours after dosing had been administered for 3 days or longer. This was repeated if the dose was escalated. Lower Limits of Quantitation (LLQ) for SK&101468 = 20 pg/mL. The lowest concentration of analyte can be measured with established acceptable accuracy and precision.

10. Pharmacokinetic Analysis: Plasma Concentrations of SK&F104557, a Circulating Metabolite of Ropinirole. [Weeks 1 -12]

    Plasma samples taken at 24 hours after dosing had been administered for 3 days or longer. This was repeated if the dose was escalated. Lower Limits of Quantitation (LLQ) for SK&104557 = 20 pg/mL. The lowest concentration of analyte can be measured with established acceptable accuracy and precision.

11. Pharmacokinetic Analysis: Plasma Concentrations of SK&F89124, a Circulating Metabolite of Ropinirole. [Weeks 1-12]

    Plasma samples taken at 24 hours after dosing had been administered for 3 days or longer. This was repeated if the dose was escalated. Lower Limits of Quantitation (LLQ) for SK&89124 = 20 pg/mL. The lowest concentration of analyte can be measured with established acceptable accuracy and precision.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• A subject will be considered eligible for inclusion in this study only if all of the following criteria apply:

At Week -1 (at the start of Screening period)

• Patients who are diagnosed with RLS according to the International RLS Study Group's (IRLSSG) Diagnostic Criteria.

• Age: Patients aged at least 18 years and under 80 years.

• Patients who have had RLS symptoms in the evening or nighttime (17:00 to 7:00 next day) for at least 20 days within one month before the start of the screening period. Patients treated for RLS before the start of the Screening period and who do not meet this criterion are considered eligible if the previous therapy can be discontinued from the Screening period.

• Patients who experience RLS symptoms requiring treatment after 17:00 but prior to bedtime.

• Gender: male and female Female of child-bearing potential will be eligible for inclusion in this study. However they must have a negative pregnancy test at the Screening visit. They agree are perform pregnancy test at the time determined and practice one of the following method of contraception from the Screening visit till the end of follow-up examination.

• Abstinence

• Oral Contraceptive, either combined or progestogen alone

• Injectable progestogen

• Implants of levonorgestrel

• Estrogenic vaginal ring

• Percutaneous contraceptive patches

• Intrauterine device (IUD) or intrauterine system (IUS) that meets the SOP effectiveness criteria as stated in the product label

• Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject

• Double barrier method: condom or occlusive cap (diaphragm or cervical / vault caps) plus spermicidal agent (foam /gel / film / cream / suppository

• Inpatient or outpatient status: Outpatient status

• Patients who are able to give informed written consent in person. For patients aged under 20 years, their legally acceptable representatives are able to give informed written consent.

At Week 0 (at the start of treatment period)

• Patients who experience RLS symptoms in the evening and nighttime (17:00 to 7:00 next day) for at least 4 days within 7 days before the start of the treatment period.

• Patients who have sleep impairment associated with RLS. Patients who answered as 3 (severe) or 4 (very severe) to Question 4 (Sleep disturbance) in the IRLS Rating Scale

• Patients whose IRLS Rating Scale total scores are 15 points or more.

Exclusion Criteria:

• Patients requiring treatment for daytime RLS symptoms (7:00 to 17:00).

• Patients with signs of secondary RLS (e.g. chronic renal failure, iron-deficiency anemia, pregnancy, rheumatoid arthritis and Parkinson's disease).

• Patients whose serum ferritin level is <10 μg/L (ng/mL) at the start of Screening period.

• Patients with following sleep disorder not associated with RLS e.g. narcolepsy, sleep terror disorder, sleep walking disorder, breathing related sleep disorder (Patients with obvious apnea in nighttime sleeping when they do not have alcohol drinking or over 15 times/hour is used to a target for apnea hypopnea index,in which case to implement polysomnography), etc.

• Patients with complication of movement disorder (e.g. Parkinson's disease, dyskinesia, dystonia, etc.).

• Patients with severe hepatic/renal/cardiac/pulmonary disorder or hematopoietic disorder.

The severity refers to Grade 3 according to "the Classification of the Severity of Adverse Experiences" (Pharmaceutical affairs Bureau/Safety Division (PAB/SD) Notification No. 80, dated 29 June 1992).

• Patients with the medical history or complication of cancer or malignant tumour.

• Patients with the medical history or complication of substance abuse (e.g. alcohol or drug) or dependency of substance for the last one year

• Patients whose diastolic blood pressure (BP) is >110 mmHg or <50 mmHg or whose systolic BP is >180 mmHg or <90 mmHg at the start of Screening period and Week0.

• Patients intolerant for ropinirole hydrochloride (HCl) or other dopamine agonists.

• Patients with the medical history of allergy to ropinirole HCl in the past.

• Patients with the medical history of Augmentation to ropinirole HCl or other dopamine agonists in the past and those who have experienced early morning RLS symptoms.

Augmentation is defined as below:

RLS appear 2 hours earlier than the pre-treatment. Symptoms become severer than the pre-treatment. Symptoms which start after less time at rest than they did before treatment. The RLS extend to other sites (e.g. arm and trunk).

• Patients without nighttime sleeping habit (e.g. night-shift worker, etc.) and those who must drastically change the habitual bedtime during the study duration.

• Patients who have participated in another clinical study of an investigational product or medical device within the last 12 weeks prior to the start of screening period.

• Female patients who are pregnant or lactating, who may be pregnant, or who plan for pregnancy during the study .

• Patients with chronic hepatitis typeB and /or typeC which is positive of hepatitis B surface antigen （HBsAg）and/or hepatitis C antibody.

• Patients who have medical conditions which, in the opinion of investigator could affect efficacy and safety assessment. This may include, but are not limited to the following disorders: diabetes, peripheral neuropathy, fibromyalgia syndrome, symptomatic orthostatic hypotension, hepatic or renal failure, pleuro-pulmonary fibrosis.

• Patients who have received treatment of an estrogen drug product and a drug that are known to substantially inhibit CYP1A2 and have changed the dose from baseline visit to Week 0.

• Others whom the investigator (sub investigator) considers ineligible for the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Fukuoka		Japan	802-0084
2	GSK Investigational Site	Fukuoka		Japan	810-0044
3	GSK Investigational Site	Fukuoka		Japan	830-0011
4	GSK Investigational Site	Hiroshima		Japan	733-0031
5	GSK Investigational Site	Kanagawa		Japan	210-0024
6	GSK Investigational Site	Osaka		Japan	550-0004
7	GSK Investigational Site	Osaka		Japan	589-0022
8	GSK Investigational Site	Osaka		Japan	599-8263
9	GSK Investigational Site	Tochigi		Japan	321-0293
10	GSK Investigational Site	Tokyo		Japan	151-0053
11	GSK Investigational Site	Tokyo		Japan	187-0041

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• GSK has concluded that it is not feasible to publish this study in a peer-reviewed scientific journal because the nature of the study is unlikely to be of interest to a journal. GSK is providing the attached study results summary with a conclusion.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00530790
• Other Study ID Numbers: 107846
• First Posted: Sep 17, 2007
• Last Update Posted: Sep 26, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Restless Legs Syndrome
• Additional relevant MeSH terms: Psychomotor Agitation; Restless Legs Syndrome; Syndrome; Ropinirole

Study Results

Participant Flow

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
Period Title: Overall Study
STARTED	35
COMPLETED	30
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
Overall Participants	35
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.2 (14.7)
Sex: Female, Male (Count of Participants)
Female	23 65.7%
Male	12 34.3%
Region of Enrollment (Number of participants) [Number]
Japan	35 100%

Outcome Measures

1. Primary Outcome

Title	Drug Related Adverse Events-On-Therapy
Time Frame	Weeks 1 - 12 Treatment Period

Outcome Measure Data

Analysis Population Description

Safety Population consisting of the subjects who took at least one dose of the study medication.

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
Measure Participants	35
Subjects with any Adverse Events	29
Nausea	14
Somnolence	5
Vomiting	5
Hypersomnia	3
Diarrhea	2
Dizziness	2
Dyspepsia	2
Fatigue	2
Stomach discomfort	2
Abdominal pain	1
Anemia	1
Insomnia	1
Irritability	1
Malaise	1
Middle Insomnia	1
Motion Sickness	1
Palpitations	1
Thirst	1

2. Secondary Outcome

Title	Change From Baseline to Week 12 in International Restless Leg Syndrome (IRLS) Rating Scale Total Score
Description	The IRLS Scale assesses the severity of sensory and motor symptoms, sleep disturbance, daytime somnolence, and impact on activities of daily living and mood. The questionnaire scores various questions and totals them using the following scale: Very severe=31-40 points, Severe=21-30 points, Moderate=11-20 points, Mild=1-10 points, None=0 points.
Time Frame	Baseline and after Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set: Subjects entered to the treatment period, except for those not fulfilling the major registration criteria, those who did not take even one dose of the study medication, and those for whom no observation data were available after starting the study treatment. Method for missing data is Last Observation Carried Forward (LOCF).

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
Measure Participants	35
IRLS assessment Score - week 0	25.3 (4.42)
IRLS assessment Score - week 12	6.0 (7.5)
Change from Baseline at week 12	-19.3 (7.68)

3. Secondary Outcome

Title	Clinical Global Impression Scale - Severity of Illness (CGI-S)
Description	The CGI-S scale measures the overall severity of illness on a 7 point scale. Normal = 1, Borderline = 2, Mildly = 3, Moderately = 4, Markedly = 5, Severely = 6, Extremely Severe = 7(no subjects scored a 7).
Time Frame	Baseline - Final assessment point

Outcome Measure Data

Analysis Population Description

Full Analysis Set Population (Baseline, Weeks 1, 2, 3, 4 = 35 subjects; Weeks 5 and 6 = 33 subjects; Week 8 = 32 subjects; Weeks 10 and 12 = 30 subjects; Final assessment point = 35 subjects). Method of Missing Data = LOCF.

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
Measure Participants	35
Baseline - Normal	0 0%
Baseline - Borderline	0 0%
Baseline - Mildly	0 0%
Baseline - Moderately	13 37.1%
Baseline - Markedly	13 37.1%
Baseline - Severely	9 25.7%
Week 1 - Normal	0 0%
Week 1 - Borderline	3 8.6%
Week 1 - Mildly	10 28.6%
Week 1 - Moderately	16 45.7%
Week 1 - Markedly	4 11.4%
Week 1 - Severely	2 5.7%
Week 2 - Normal	3 8.6%
Week 2 - Borderline	7 20%
Week 2 - Mildly	12 34.3%
Week 2 - Moderately	10 28.6%
Week 2 - Markedly	2 5.7%
Week 2 - Severely	1 2.9%
Week 3 - Normal	11 31.4%
Week 3 - Borderline	7 20%
Week 3 - Mildly	8 22.9%
Week 3 - Moderately	7 20%
Week 3 - Markedly	1 2.9%
Week 3 - Severely	1 2.9%
Week 4 - Normal	9 25.7%
Week 4 - Borderline	9 25.7%
Week 4 - Mildly	10 28.6%
Week 4 - Moderately	5 14.3%
Week 4 - Markedly	1 2.9%
Week 4 - Severely	1 2.9%
Week 5 - Normal	11 31.4%
Week 5 - Borderline	6 17.1%
Week 5 - Mildly	11 31.4%
Week 5 - Moderately	4 11.4%
Week 5 - Markedly	1 2.9%
Week 5 - Severely	0 0%
Week 6 - Normal	13 37.1%
Week 6 - Borderline	4 11.4%
Week 6 - Mildly	11 31.4%
Week 6 - Moderately	4 11.4%
Week 6 - Markedly	1 2.9%
Week 6 - Severely	0 0%
Week 8 - Normal	10 28.6%
Week 8 - Borderline	10 28.6%
Week 8 - Mildly	8 22.9%
Week 8 - Moderately	3 8.6%
Week 8 - Markedly	1 2.9%
Week 8 - Severely	0 0%
Week 10 - Normal	15 42.9%
Week 10 - Borderline	5 14.3%
Week 10 - Mildly	8 22.9%
Week 10 - Moderately	1 2.9%
Week 10 - Markedly	1 2.9%
Week 10 - Severely	0 0%
Week 12 - Normal	16 45.7%
Week 12 - Borderline	3 8.6%
Week 12 - Mildly	10 28.6%
Week 12 - Moderately	0 0%
Week 12 - Markedly	1 2.9%
Week 12 - Severely	0 0%
Final assessment point - Normal	17 48.6%
Final assessment point - Borderline	3 8.6%
Final assessment point - Mildly	12 34.3%
Final assessment point - Moderately	1 2.9%
Final assessment point - Markedly	1 2.9%
Final assessment point - Severely	1 2.9%

4. Secondary Outcome

Title	Clinical Global Impression Global Improvement (CGI-GI)
Description	CGI-GI is a 7 point scale assessing Global Improvement. 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, 7 = Very much worse (no patients scored a 5, 6, or 7).
Time Frame	Baseline - Final assessment point

Outcome Measure Data

Analysis Population Description

Full Analysis Set Population (Weeks 1, 2, 3, and 4 = 35 subjects; Weeks 5 and 6 = 33 subjects; Week 8 = 32 subjects; Week 10, 12 = 30 subjects; Final assessment point = 35 subjects). Method for missing date is LOCF.

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
Measure Participants	35
Week 1 - Very Much Improved	4 11.4%
Week 1 - Much Improved	12 34.3%
Week 1 - Minimally Improved	13 37.1%
Week 1 - No Change	6 17.1%
Week 2 - Very Much Improved	15 42.9%
Week 2 - Much Improved	9 25.7%
Week 2 - Minimally Improved	9 25.7%
Week 2 - No Change	2 5.7%
Week 3 - Very Much Improved	21 60%
Week 3 - Much Improved	7 20%
Week 3 - Minimally Improved	6 17.1%
Week 3 - No Change	1 2.9%
Week 4 - Very Much Improved	21 60%
Week 4 - Much Improved	7 20%
Week 4 - Minimally Improved	6 17.1%
Week 4 - No Change	1 2.9%
Week 5 - Very Much Improved	21 60%
Week 5 - Much Improved	6 17.1%
Week 5 - Minimally Improved	6 17.1%
Week 5 - No Change	0 0%
Week 6 - Very Much Improved	22 62.9%
Week 6 - Much Improved	7 20%
Week 6 - Minimally Improved	4 11.4%
Week 6 - No Change	0 0%
Week 8 - Very Much Improved	24 68.6%
Week 8 - Much Improved	6 17.1%
Week 8 - Minimally Improved	2 5.7%
Week 8 - No Change	0 0%
Week 10 - Very Much Improved	22 62.9%
Week 10 - Much Improved	6 17.1%
Week 10 - Minimally Improved	2 5.7%
Week 10 - No Change	0 0%
Week 12 - Very Much Improved	25 71.4%
Week 12 - Much Improved	4 11.4%
Week 12 - Minimally Improved	0 0%
Week 12 - No Change	1 2.9%
Final assessment point - Very Much Improved	27 77.1%
Final assessment point - Much Improved	5 14.3%
Final assessment point - Minimally Improved	1 2.9%
Final assessment point - No Change	2 5.7%

5. Secondary Outcome

Title	Change From Baseline at Week 12/Early Withdrawal (EW) in Pittsburgh Sleep Quality Index (PSQI) Total Score
Description	The PSQI generates seven scores that correspond to different domains. Each component score ranges from 0 (no difficulty) to 3 (severe difficulty). The domain scores are totaled to produce a global score (range of 0-21). A PSQI global score > 5 is considered to be suggestive of significant sleep disturbance.
Time Frame	Baseline - Week 12/EW

Outcome Measure Data

Analysis Population Description

Full Analysis Set(FAS)

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
Measure Participants	35
PSQI Total Score at Baseline	9.4 (3.20)
PSQI Total Score at Week 12/EW	5.4 (2.89)
Change from Baseline at Week 12/EW	-4.2 (3.94)

6. Secondary Outcome

Title	Change From Baseline to Week 12/EW in Pittsburgh Sleep Quality Index (PSQI) Total Score by Domains
Description	The PSQI generates seven scores that correspond to different domains. Each component score ranges from 0 (no difficulty) to 3 (severe difficulty). The domain scores are totaled to produce a global score (range of 0-21). A PSQI global score > 5 is considered to be suggestive of significant sleep disturbance.
Time Frame	Baseline - Week 12/EW

Outcome Measure Data

Analysis Population Description

Full Analysis Set(FAS)

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
Measure Participants	35
Sleep Quality - Baseline	2.0 (0.62)
Sleep Quality - Week 12/EW	1.2 (0.77)
Sleep Quality - Change from Baseline	-0.9 (0.78)
Duration getting to sleep - Baseline	2.0 (1.04)
Duration getting to sleep - Week 12/EW	1.0 (0.88)
Duration getting to sleep - Change from Baseline	-1.1 (1.09)
Sleep Duration - Baseline	1.9 (0.77)
Sleep Duration - Week 12/EW	1.5 (0.79)
Sleep Duration - Change from Baseline	-0.4 (0.74)
Sleep Adequacy - Baseline	0.9 (1.11)
Sleep Adequacy - Week 12/EW	0.4 (0.70)
Sleep Adequacy - Change from Baseline	-0.6 (1.19)
Sleep Disturbance - Baseline	1.2 (0.43)
Sleep Disturbance - Week 12/EW	0.9 (0.55)
Sleep Disturbance - Change from Baseline	-0.3 (0.60)
Use of Sleeping pill - Baseline	0.4 (1.01)
Use of Sleeping pill - Week 12/EW	0.0 (0.00)
Use of Sleeping pill - Change from Baseline	-0.4 (1.03)
Somnolence - Baseline	1.0 (0.92)
Somnolence - Week 12/EW	0.5 (0.62)
Somnolence - Change from Baseline	-0.5 (0.97)

7. Secondary Outcome

Title	Change From Baseline at Week 12/Early Withdrawal (EW) in Johns Hopkins Restless Leg Syndrome Quality of Life Questionnaire (RLSQOL) on the Overall Life Impact Score
Description	The RLSQOL scale consists of 18 items, 13 of which are scored on a 5-point scale. Ten of the items can be summed to the overall life impact score, which can be transformed to a 0-100 score. Mild = 84.48, Moderate = 62.93, or Severe = 37.47
Time Frame	Baseline and Week 12/EW

Outcome Measure Data

Analysis Population Description

Full Analysis Set(FAS)

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
Measure Participants	33
RLSQOL Overall Life Impact Score - Baseline	65.29 (14.499)
RLSQOL Overall Life Impact Score - Week 12	89.09 (13.431)
Change from Baseline	23.94 (16.759)

8. Primary Outcome

Title	Haematology Clinical Lab Values Change From Baseline
Description	Standard units of measure vary. Therefore, Mean Change is represented in Standard Units: Hematocrit = SI unit of GSK; Hemoglobin = G/L; Platelet count, White Blood Cell count = GI/L; Red Blood Cell count = TI/L. n = number of subjects evaluated. EW = Early Withdrawal.
Time Frame	Baseline - Week 13 (Follow-up)

Outcome Measure Data

Analysis Population Description

Safety Population (Week 4 = 35 subjects, Week 8 = 32 subjects, Week 12 = 30 subjects, Week 12/EW = 33 subjects, Week 13 (Follow-up) = 35 subjects whose labs were evaluated).

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
Measure Participants	35
Hemoglobin (G/L) - week 4	-1.2 (6.97)
Hemoglobin (G/L) - week 8	-2.7 (8.79)
Hemoglobin (G/L) - week 12	-1.0 (4.84)
Hemoglobin (G/L) - week 12/EW	-0.8 (4.69)
Hemoglobin (G/L)- week 13	-2.2 (7.30)
Hematocrit (SI) - week 4	-0.0033 (0.01972)
Hematocrit (SI) - week 8	-0.0074 (0.02470)
Hematocrit (SI) - week 12	-0.0021 (0.01174)
Hematocrit (SI) - week 12/EW	-0.0016 (0.01148)
Hematocrit (SI) - week 13	-0.0063 (0.01929)
Platelet Count (GI/L) - week 4	14.5 (26.86)
Platelet Count (GI/L) - week 8	11.7 (27.92)
Platelet Count (GI/L) - week 12	8.5 (22.79)
Platelet Count (GI/L) - week 12/EW	8.8 (21.74)
Platelet Count (GI/L) - week 13	10.7 (41.48)
Red Blood Cell Count (TI/L) - week 4	-0.043 (0.2139)
Red Blood Cell Count (TI/L) - week 8	-0.084 (0.2701)
Red Blood Cell Count (TI/L) - week 12	-0.015 (0.1469)
Red Blood Cell Count (TI/L) - week 12/EW	-0.011 (0.1411)
Red Blood Cell Count (TI/L) - week 13	-0.050 (0.2140)
White Blood Cell Count (GI/L) - week 4	-0.191 (1.1655)
White Blood Cell Count (GI/L) - week 8	-0.268 (1.8694)
White Blood Cell Count (GI/L) - week 12	-0.577 (1.4972)
White Blood Cell Count (GI/L) - week 12/EW	-0.516 (1.4407)
White Blood Cell Count (GI/L) - week 13	-0.624 (1.4914)

9. Primary Outcome

Title	Blood Chemistry Clinical Lab Values Change From Baseline
Description	Mean Change in Standard Units of Measure: Albumin, Total Protein=G/L; Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Lactate Dehydrogenase, Creatine Phosphokinase, Gamma Glutamyl Transferase=IU/L; Total Bilirubin, Creatinine=UMOL/L; Blood Urea Nitrogen, Cholesterol, Chloride, Sodium, Potassium=MMOL/L; Prolactin=MCG/L
Time Frame	Baseline - Week 13 (Follow-up)

Outcome Measure Data

Analysis Population Description

Safety Population (Week 4 = 35 subjects, Week 8 = 32 subjects, Week 12 = 30 subjects, Week 12/EW = 33 subjects, Week 13 (Follow-up) = 35 subjects whose labs were evaluated).

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
Measure Participants	35
Albumin (G/L) - week 4	-1.0 (2.35)
Albumin (G/L) - week 8	-1.4 (2.64)
Albumin (G/L) - week 12	-0.7 (2.34)
Albumin (G/L) - week 12/EW	-0.6 (2.28)
Albumin (G/L) - week 13	-1.3 (2.33)
Alkaline Phosphatase (IU/L) - week 4	5.2 (30.53)
Alkaline Phosphatase (IU/L) - week 8	4.2 (26.94)
Alkaline Phosphatase (IU/L) - week 12	13.2 (29.35)
Alkaline Phosphatase (IU/L) - week 12/EW	13.4 (28.52)
Alkaline Phosphatase (IU/L) - week 13	16.0 (36.45)
Alanine Amino Transferase (IU/L) - week 4	-0.3 (3.80)
Alanine Amino Transferase (IU/L) - week 8	-0.7 (5.08)
Alanine Amino Transferase (IU/L) - week 12	1.7 (4.66)
Alanine Amino Transferase - week 12/EW	1.8 (4.56)
Alanine Amino Transferase - week 13	1.4 (6.36)
Aspartate Amino Transferase(IU/L) - week 4	0.4 (4.55)
Aspartate Amino Transferase (IU/L) - week 8	-0.2 (4.07)
Aspartate Amino Transferase (IU/L) - week 12	1.3 (4.57)
Aspartate Amino Transferase (IU/L) - week 12/EW	1.5 (4.51)
Aspartate Amino Transferase (IU/L) - week 13	0.6 (4.35)
Total Bilirubin (UMOL/L) - week 4	0.147 (3.1686)
Total Bilirubin (UMOL/L) - week 8	-0.588 (2.5180)
Total Bilirubin (UMOL/L) - week 12	0.513 (3.4244)
Total Bilirubin (UMOL/L) - week 12/EW	0.311 (3.3513)
Total Bilirubin (UMOL/L) - week 13	-1.173 (3.7959)
Blood Urea Nitrogen (MMOL/L) - week 4	-0.14382 (1.079245)
Blood Urea Nitrogen (MMOL/L) - week 8	-0.06024 (0.862798)
Blood Urea Nitrogen (MMOL/L) - week 12	0.25704 (1.076664)
Blood Urea Nitrogen (MMOL/L) - week 12/EW	0.30399 (1.043047)
Blood Urea Nitrogen (MMOL/L) - week 13	0.32334 (0.974457)
Cholesterol (MMOL/L) - week 4	-0.093835 (0.5322345)
Cholesterol (MMOL/L) - week 8	-0.190717 (0.4337538)
Cholesterol (MMOL/L) - week 12	0.151712 (0.5674075)
Cholesterol (MMOL/L) - week 12/EW	0.146540 (0.5494743)
Cholesterol - week 13	-0.107873 (0.5638668)
Chloride(MMOL/L) - week 4	0.1 (1.78)
Chloride (MMOL/L) - week 8	0.3 (2.07)
Chloride (MMOL/L) - week 12	-0.3 (1.81)
Chloride (MMOL/L) - week 12/EW	-0.2 (1.92)
Chloride (MMOL/L) - week 13	-0.1 (2.30)
Lactate Dehydrogenase (IU/L) - week 4	0.3 (22.02)
Lactate Dehydrogenase (IU/L) - week 8	-1.3 (16.74)
Lactate Dehydrogenase (IU/L) - week 12	2.0 (25.96)
Lactate Dehydrogenase (IU/L) - week 12/EW	2.7 (25.06)
Lactate Dehydrogenase (IU/L) - week 13	-2.2 (18.78)
Sodium (MMOL/L) - week 4	-0.4 (1.37)
Sodium (MMOL/L) - week 8	-0.2 (1.36)
Sodium (MMOL/L) - week 12	0.0 (1.11)
Sodium (MMOL/L) - week 12/EW	-0.0 (1.07)
Sodium (MMOL/L) - week 13	-0.2 (1.29)
Prolactin (MCG/L) - week 4	0.80 (7.003)
Prolactin (MCG/L) - week 8	0.51 (7.229)
Prolactin (MCG/L) - week 12	0.20 (6.770)
Prolactin (MCG/L) - week 12/EW	0.22 (6.466)
Prolactin (MCG/L) - week 13	1.14 (7.144)
Total Protein (G/L) - week 4	-1.1 (3.73)
Total Protein (G/L) - week 8	-1.7 (4.03)
Total Protein (G/L) - week 12	-0.8 (3.32)
Total Protein (G/L) - week 12/EW	-0.8 (3.20)
Total Protein (G/L) - week 13	-2.2 (3.45)
Creatine Phosphokinase (IU/L) - week 4	72.3 (533.72)
Creatine Phosphokinase (IU/L) - week 8	-15.8 (100.86)
Creatine Phosphokinase (IU/L) - week 12	-0.6 (115.92)
Creatine Phosphokinase (IU/L) - week 12/EW	-0.2 (110.40)
Creatine Phosphokinase (IU/L) - week 13	-1.9 (124.63)
Creatinine (UMOL/L) - week 4	1.3134 (4.76710)
Creatinine (UMOL/L) - week 8	0.5801 (7.23972)
Creatinine (UMOL/L) - week 12	1.0019 (4.73343)
Creatinine (UMOL/L) - week 12/EW	1.0447 (4.60113)
Creatinine (UMOL/L) - week 13	1.6417 (4.96904)
Gamma Glutamyl Transferase (IU/L) - week 4	1.5 (17.56)
Gamma Glutamyl Transferase (IU/L) - week 8	-1.4 (11.68)
Gamma Glutamyl Transferase (IU/L) - week 12	1.9 (14.56)
Gamma Glutamyl Transferase (IU/L) - week 12/EW	2.6 (14.26)
Gamma Glutamyl Tranferase (IU/L) - week 13	0.1 (10.10)
Potassium (MMOL/L) - week 4	0.07 (0.280)
Potassium (MMOL/L) - week 8	0.05 (0.363)
Potassium (MMOL/L) - week 12	0.09 (0.305)
Potassium (MMOL/L) - week 12/EW	0.10 (0.293)
Potassium (MMOL/L) - week 13	0.06 (0.308)

10. Primary Outcome

Title	Urinalysis Clinical Lab Values
Description	Dipstick test values: Neg Value, Trace, +1, +2, +3. No subjects tested higher than +3.
Time Frame	Baseline - Week 13 (Follow-up)

Outcome Measure Data

Analysis Population Description

Safety Population (Baseline, Week 4 = 35 subjects, Week 8 = 32 subjects, Week 12 = 30 subjects, Week 12/EW = 33 subjects, Week 13 [Follow-up] = 35 subjects evaluated).

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
Measure Participants	35
Urine Urobilinogen - Baseline: Neg Value	0 0%
Urine Urobilinogen - Baseline: Trace	35 100%
Urine Urobilinogen - Baseline: +1	0 0%
Urine Urobilinogen - Baseline: +2	0 0%
Urine Urobilinogen - Baseline: +3	0 0%
Urine Urobilinogen - week 4: Neg Value	0 0%
Urine Urobilinogen - week 4: Trace	35 100%
Urine Urobilinogen - week 4: +1	0 0%
Urine Urobilinogen - week 4: +2	0 0%
Urine Urobilinogen - week 4: +3	0 0%
Urine Urobilinogen - week 8: Neg Value	0 0%
Urine Urobilinogen - week 8: Trace	32 91.4%
Urine Urobilinogen - week 8: +1	0 0%
Urine Urobilinogen - week 8: +2	0 0%
Urine Urobilinogen - week 8: +3	0 0%
Urine Urobilinogen - week 12: Neg Value	0 0%
Urine Urobilinogen - week 12: Trace	30 85.7%
Urine Urobilinogen - week 12: +1	0 0%
Urine Urobilinogen - week 12: +2	0 0%
Urine Urobilinogen - week 12: +3	0 0%
Urine Urobilinogen - week 12/EW: Neg Value	0 0%
Urine Urobilinogen - week 12/EW: Trace	33 94.3%
Urine Urobilinogen - week 12/EW: +1	0 0%
Urine Urobilinogen - week 12/EW: +2	0 0%
Urine Urobilinogen - week 12/EW: +3	0 0%
Urine Urobilinogen - week 13: Neg Value	0 0%
Urine Urobilinogen - week 13: Trace	35 100%
Urine Urobilinogen - week 13: +1	0 0%
Urine Urobilinogen - week 13: +2	0 0%
Urine Urobilinogen - week 13: +3	0 0%
Urine Protein - Baseline: Neg Value	34 97.1%
Urine Protein - Baseline: Trace	1 2.9%
Urine Protein - Baseline: +1	0 0%
Urine Protein - Baseline: +2	0 0%
Urine Protein - Baseline: +3	0 0%
Urine Protein - Week 4: Neg Value	35 100%
Urine Protein - Week 4: Trace	0 0%
Urine Protein - Week 4: +1	0 0%
Urine Protein - Week 4: +2	0 0%
Urine Protein - Week 4: +3	0 0%
Urine Protein - Week 8: Neg Value	31 88.6%
Urine Protein - Week 8: Trace	1 2.9%
Urine Protein - Week 8: +1	0 0%
Urine Protein - Week 8: +2	0 0%
Urine Protein - Week 8: +3	0 0%
Urine Protein - Week 12: Neg Value	30 85.7%
Urine Protein - Week 12: Trace	0 0%
Urine Protein - Week 12: +1	0 0%
Urine Protein - Week 12: +2	0 0%
Urine Protein - Week 12: +3	0 0%
Urine Protein - Week 12/EW: Neg Value	33 94.3%
Urine Protein - Week 12/EW: Trace	0 0%
Urine Protein - Week 12/EW: +1	0 0%
Urine Protein - Week 12/EW: +2	0 0%
Urine Protein - Week 12/EW: +3	0 0%
Urine Protein - Week 13: Neg Value	35 100%
Urine Protein - Week 13: Trace	0 0%
Urine Protein - Week 13: +1	0 0%
Urine Protein - Week 13: +2	0 0%
Urine Protein - Week 13: +3	0 0%
Urine Occult Blood - Baseline: Neg Value	27 77.1%
Urine Occult Blood - Baseline: Trace	5 14.3%
Urine Occult Blood - Baseline: +1	3 8.6%
Urine Occult Blood - Baseline: +2	0 0%
Urine Occult Blood - Baseline: +3	0 0%
Urine Occult Blood - Week 4: Neg Value	20 57.1%
Urine Occult Blood - Week 4: Trace	7 20%
Urine Occult Blood - Week 4: +1	6 17.1%
Urine Occult Blood - Week 4: +2	2 5.7%
Urine Occult Blood - Week 4: +3	0 0%
Urine Occult Blood - Week 8: Neg Value	25 71.4%
Urine Occult Blood - Week 8: Trace	3 8.6%
Urine Occult Blood - Week 8: +1	3 8.6%
Urine Occult Blood - Week 8: +2	0 0%
Urine Occult Blood - Week 8: +3	1 2.9%
Urine Occult Blood - Week 12: Neg Value	23 65.7%
Urine Occult Blood - Week 12: Trace	4 11.4%
Urine Occult Blood - Week 12: +1	2 5.7%
Urine Occult Blood - Week 12: +2	1 2.9%
Urine Occult Blood - Week 12: +3	0 0%
Urine Occult Blood - Week 12/EW: Neg Value	25 71.4%
Urine Occult Blood - Week 12/EW: Trace	5 14.3%
Urine Occult Blood - Week 12/EW: +1	2 5.7%
Urine Occult Blood - Week 12/EW: +2	1 2.9%
Urine Occult Blood - Week 12/EW: +3	0 0%
Urine Occult Blood - Week 13: Neg Value	26 74.3%
Urine Occult Blood - Week 13: Trace	3 8.6%
Urine Occult Blood - Week 13: +1	6 17.1%
Urine Occult Blood - Week 13: +2	0 0%
Urine Occult Blood - Week 13: +3	0 0%
Urine Glucose - Baseline: Neg Value	35 100%
Urine Glucose - Baseline: Trace	0 0%
Urine Glucose - Baseline: +1	0 0%
Urine Glucose - Baseline: +2	0 0%
Urine Glucose - Baseline: +3	0 0%
Urine Glucose - Week 4: Neg Value	34 97.1%
Urine Glucose - Week 4: Trace	0 0%
Urine Glucose - Week 4: +1	1 2.9%
Urine Glucose - Week 4: +2	0 0%
Urine Glucose - Week 4: +3	0 0%
Urine Glucose - Week 8: Neg Value	31 88.6%
Urine Glucose - Week 8: Trace	1 2.9%
Urine Glucose - Week 8: +1	0 0%
Urine Glucose - Week 8: +2	0 0%
Urine Glucose - Week 8: +3	0 0%
Urine Glucose - Week 12: Neg Value	29 82.9%
Urine Glucose - Week 12: Trace	1 2.9%
Urine Glucose - Week 12: +1	0 0%
Urine Glucose - Week 12: +2	0 0%
Urine Glucose - Week 12: +3	0 0%
Urine Glucose - Week 12/EW: Neg Value	32 91.4%
Urine Glucose - Week 12/EW: Trace	1 2.9%
Urine Glucose - Week 12/EW: +1	0 0%
Urine Glucose - Week 12/EW: +2	0 0%
Urine Glucose - Week 12/EW: +3	0 0%
Urine Glucose - Week 13: Neg Value	35 100%
Urine Glucose - Week 13: Trace	0 0%
Urine Glucose - Week 13: +1	0 0%
Urine Glucose - Week 13: +2	0 0%
Urine Glucose - Week 13: +3	0 0%

11. Primary Outcome

Title	12-Lead Electrocardiogram (ECG) Findings Transitions From Baseline
Description	Baseline Finding/Time Period Finding. Abbreviations: N = normal; A = abnormal; CS = clinically significant; NCS = not clinically significant. Options include N/N, N/ANCS, N/ACS, ANCS/N, ANCS/ANCS, ANCS/ACS, ACS/N, ACS/ANCS, and ACS/ACS.
Time Frame	Baseline, Week 4, 8, 12, 13 (Follow-up)

Outcome Measure Data

Analysis Population Description

Safety Population - (Baseline = 35 subjects, Week 4 = 33 subjects, Week 8 = 31 subjects, Week 12/EW = 33 subjects and Week 13 [Follow-up] = 35 subjects evaluated).

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
Measure Participants	35
Baseline: N; Baseline: N	29 82.9%
Baseline: N; Baseline: ANCS	0 0%
Baseline: N; Baseline: ACS	0 0%
Baseline: ANCS; Baseline: N	0 0%
Baseline: ANCS; Baseline: ANCS	5 14.3%
Baseline: ANCS; Baseline: ACS	0 0%
Baseline: ACS; Baseline: N	0 0%
Baseline; ACS; Baseline: ANCS	0 0%
Baseline: ACS ; Baseline: ACS	1 2.9%
Baseline: N; Week 4: N	27 77.1%
Baseline: N; Week 4: ANCS	1 2.9%
Baseline: N; Week 4: ACS	0 0%
Baseline: ANCS; Week 4: N	2 5.7%
Baseline: ANCS; Week 4: ANCS	1 2.9%
Baseline: ANCS; Week 4: ACS	1 2.9%
Baseline: ACS; Week 4: N	0 0%
Baseline: ACS; Week 4: ANCS	0 0%
Baseline: ACS; Week 4: ACS	1 2.9%
Baseline: N; Week 8: N	24 68.6%
Baseline: N; Week 8: ANCS	2 5.7%
Baseline: N; Week 8: ACS	0 0%
Baseline: ANCS; Week 8: N	2 5.7%
Baseline: ANCS; Week 8: ANCS	1 2.9%
Baseline: ANCS; Week 8: ACS	1 2.9%
Baseline: ACS; Week 8: N	0 0%
Baseline: ACS; Week 8: ANCS	1 2.9%
Baseline: ACS; Week 8: ACS	0 0%
Baseline: N; Week 12/EW: N	27 77.1%
Baseline: N; Week 12/EW: ANCS	0 0%
Baseline: N; Week 12/EW: ACS	0 0%
Baseline: ANCS; Week 12/EW: N	4 11.4%
Baseline: ANCS; Week 12/EW: ANCS	0 0%
Baseline: ANCS; Week 12/EW: ACS	1 2.9%
Baseline: ACS; Week 12/EW: N	0 0%
Baseline: ACS; Week 12/EW: ANCS	0 0%
Baseline: ACS; Week 12/EW: ACS	1 2.9%
Baseline: N; Week 13: N	27 77.1%
Baseline: N; Week 13: ANCS	2 5.7%
Baseline: N; Week 13: ACS	0 0%
Baseline: ANCS; Week 13: N	2 5.7%
Baseline: ANCS; Week 13: ANCS	2 5.7%
Baseline: ANCS; Week 13: ACS	1 2.9%
Baseline: ACS; Week 13: N	0 0%
Baseline: ACS; Week 13: ANCS	0 0%
Baseline: ACS; Week 13: ACS	1 2.9%

12. Primary Outcome

Title	Vital Signs and Body Weight Change From Baseline
Description	Units of Measure Vary: Weight = kg; Semi-supine and Standing Systolic and Diastolic BP = mmHg; Semi-supine and Standing Pulse Rate = bpm; EW = early withdrawal; Semi-supine = lying down; Orthostatic = lying, sitting, and standing.
Time Frame	Baseline to Week 12/EW

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
Measure Participants	33
Weight (Kg)	0.5 (1.33)
Semi-Supine Systolic BP (mmHg)	2.7 (10.68)
Semi-Supine Diastolic BP (mmHg)	2.6 (7.25)
Semi-Supine Pulse Rate (bpm)	0.8 (9.11)
Standing Systolic BP (mmHg)	-0.7 (10.86)
Standing Diastolic BP (mmHg)	0.8 (7.64)
Standing Pulse Rate (bpm)	1.1 (9.94)
Orthostatic Systolic BP (mmHg)	-1.5 (8.50)
Orthostatic Diastolic BP (mmHg)	4.3 (5.58)
Orthostatic Pulse Rate (bpm)	9.2 (9.15)

13. Secondary Outcome

Title	Change From Baseline at Week 12/Early Withdrawal (EW) in Profile of Mood Status (POMS)
Description	The POMS Standard form contains 65 items (0-232). The respondent rates each item on a 5-point scale, ranging from "Not at all (0)" to "Extremely (4)." The assessment measures six identified mood factors: Tension-Anxiety Depression-Dejection Anger-Hostility Vigor-Activity Fatigue-Inertia Confusion-Bewilderment
Time Frame	Baseline and Week 12/EW

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
Measure Participants	33
POMS - Baseline	59.2 (21.59)
POMS - Week 12/EW	48.0 (18.69)
Change from Baseline	-10.4 (14.46)

14. Secondary Outcome

Title	Change From Baseline at Week 12/Early Withdrawal (EW) in Hospital Anxiety and Depression Scale (HADS)
Description	Self screening questionnaire that requires the first response to questions. Questionnaire consists of 14 questions, seven for anxiety "0-21" and seven for depression "0-21". Questions are answered on a four point scale from 0-3; Items 1, 3, 5, 6, 8, 10, 11, and 13 are reversed for summation.
Time Frame	Baseline - Week 12/EW

Outcome Measure Data

Analysis Population Description

FAS: Subpopulation: HADS Anxiety population, N = 15; HADS Depression population, N = 31. Patients in the FAS population who also have a baseline anxiety domain score of 8 or greater and patients with a baseline depression domain score of 8 or greater will be included in the HADS Anxiety Population and the HADS Depression Population, respectively.

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
Measure Participants	35
Anxiety-HADS Anxiety Population - Baseline	9.3 (1.50)
Anxiety-HADS Anxiety Population - Week 12/EW	7.7 (2.39)
Change from Baseline for Anxiety Population	-1.8 (2.58)
Depression-HADS Depression Population -Baseline	9.7 (1.42)
Depression-HADS Depression Population-Week 12/EW	9.5 (1.57)
Change from Baseline for Depression Population	-0.1 (1.77)

15. Secondary Outcome

Title	Pharmacokinetic Analysis: Plasma Concentrations of SK&F101468, an Unchanged Form of Ropinirole.
Description	Plasma samples taken at 24 hours after dosing had been administered for 3 days or longer. This was repeated if the dose was escalated. Lower Limits of Quantitation (LLQ) for SK&101468 = 20 pg/mL. The lowest concentration of analyte can be measured with established acceptable accuracy and precision.
Time Frame	Weeks 1-12

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Population: subjects who underwent blood sampling for measuring the trough plasma drug concentrations, excluding those who did not fulfill inclusion criteria, those who were considered to affect the evaluation of the PK research due to drug incompliance or other protocol violation.

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
Measure Participants	35
35 subjects who received 0.5 mg of Study drug	310.01 (188.460)
27subjects who received 1 mg of Study drug	500.97 (293.344)
11 subjects who received 2 mg of Study drug	968.36 (696.327)
2 subjects who received 3 mg of Study drug	1294.55 (442.861)
2 subjects who received 4 mg of Study drug	1198.10 (362.463)

16. Secondary Outcome

Title	Pharmacokinetic Analysis: Plasma Concentrations of SK&F104557, a Circulating Metabolite of Ropinirole.
Description	Plasma samples taken at 24 hours after dosing had been administered for 3 days or longer. This was repeated if the dose was escalated. Lower Limits of Quantitation (LLQ) for SK&104557 = 20 pg/mL. The lowest concentration of analyte can be measured with established acceptable accuracy and precision.
Time Frame	Weeks 1 -12

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
Measure Participants	35
35 subjects who received 0.5 mg of Study drug	324.65 (134.576)
27 subjects who received 1 mg of Study drug	615.91 (259.145)
11 subjects who received 2 mg of Study drug	1320.31 (523.622)
2 subjects who received 3 mg of Study drug	1666.65 (325.764)
2 subjects who received 4 mg of Study drug	2541.95 (198.202)

17. Secondary Outcome

Title	Pharmacokinetic Analysis: Plasma Concentrations of SK&F89124, a Circulating Metabolite of Ropinirole.
Description	Plasma samples taken at 24 hours after dosing had been administered for 3 days or longer. This was repeated if the dose was escalated. Lower Limits of Quantitation (LLQ) for SK&89124 = 20 pg/mL. The lowest concentration of analyte can be measured with established acceptable accuracy and precision.
Time Frame	Weeks 1-12

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
Measure Participants	35
2 subjects who received 0.5 mg of Study drug	22.45 (3.465)
11 subjects who received 1 mg of Study drug	30.37 (10.227)
11 subjects who received 2 mg of Study drug	42.75 (17.286)
2 subjects who received 3 mg of Study drug	46.80 (8.202)
2 subjects who received 4 mg of Study drug	72.05 (2.051)

Adverse Events

Arm/Group Title	Ropinirole CR-RLS
Arm/Group Description	Subjects who took oral Ropinirole CR-RLS once daily 1-2 hours before onset of Restless Legs Syndrome (RLS) symptoms (after 4pm). Initial dose level was 0.5 mg/day and increased weekly by 1 mg/day until sufficient efficacy was obtained without any tolerability issues. Treatment period was 12 weeks. Maximum dose level was 6 mg per day.
All Cause Mortality
	Ropinirole CR-RLS
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ropinirole CR-RLS
	Affected / at Risk (%)	# Events
Total	0/35 (0%)
Other (Not Including Serious) Adverse Events
	Ropinirole CR-RLS
	Affected / at Risk (%)	# Events
Total	33/35 (94.3%)
Blood and lymphatic system disorders
Anemia	2/35 (5.7%)
Cardiac disorders
Palpitations	1/35 (2.9%)
Ear and labyrinth disorders
Motion sickness	1/35 (2.9%)
Tinnitus	1/35 (2.9%)
Gastrointestinal disorders
Nausea	15/35 (42.9%)
Vomiting	5/35 (14.3%)
Constipation	2/35 (5.7%)
Diarrhea	2/35 (5.7%)
Dyspepsia	2/35 (5.7%)
Stomach Discomfort	2/35 (5.7%)
Abdominal pain	1/35 (2.9%)
Abdominal Pain upper	1/35 (2.9%)
Abdominal tenderness	1/35 (2.9%)
Gingival pain	1/35 (2.9%)
General disorders
Dizziness	3/35 (8.6%)
Fatigue	2/35 (5.7%)
Irritability	1/35 (2.9%)
Local Swelling	1/35 (2.9%)
Malaise	1/35 (2.9%)
Non-cardiac chest pain	1/35 (2.9%)
Pyrexia	1/35 (2.9%)
Thirst	1/35 (2.9%)
Infections and infestations
Gingivitis	2/35 (5.7%)
Injury, poisoning and procedural complications
Chillblains	1/35 (2.9%)
Vertebral injury	1/35 (2.9%)
Wound	1/35 (2.9%)
Investigations
Blood urine present	1/35 (2.9%)
Musculoskeletal and connective tissue disorders
Arthritis	1/35 (2.9%)
Back pain	1/35 (2.9%)
Musculoskeletal stiffness	1/35 (2.9%)
Myalgia	1/35 (2.9%)
Nervous system disorders
Paraesthesia	1/35 (2.9%)
Tension headache	1/35 (2.9%)
Psychiatric disorders
Somnolence	5/35 (14.3%)
Hypersomnia	3/35 (8.6%)
Initial insomnia	1/35 (2.9%)
Insomnia	1/35 (2.9%)
Middle insomnia	1/35 (2.9%)
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis	12/35 (34.3%)
Pharyngolaryngeal pain	1/35 (2.9%)
Rhinitis allergic	1/35 (2.9%)
Upper Respiratory tract inflammation	1/35 (2.9%)
Skin and subcutaneous tissue disorders
Cold Sweat	1/35 (2.9%)
Pruritus	1/35 (2.9%)
Rash	1/35 (2.9%)
Skin tightness	1/35 (2.9%)
Tenosynovitis	1/35 (2.9%)

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 centers of the multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.