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

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)

Population: 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).

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)

Population: 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).

Time frame: Weeks 1 - 12 Treatment Period

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

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)

Population: 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).

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

Time frame: Baseline - Week 13 (Follow-up)

Population: 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).

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

Population: Safety Population

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

Population: 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.

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

Population: Full Analysis Set(FAS)

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

Population: Full Analysis Set(FAS)

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

Population: Full Analysis Set

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

Population: Full Analysis Set(FAS)

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

Population: 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).

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: PK Population

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

Population: PK Population