Clinical Evaluation of Ropinirole PR/XR Tablets in Monotherapy for Parkinson's Disease (PD)

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT00434304

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

5.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study was designed to evaluate the pharmacokinetic profile, safety and efficacy in Parkinson's Disease patients.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease	Drug: Ropinirole prolonged release/extended release(PR/XR)	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

62 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Clinical Evaluation of Ropinirole PR/XR Tablets in Monotherapy for Parkinson's Disease - an Open-Label, Uncontrolled Study -

Study Start Date :

Apr 9, 2007

Actual Primary Completion Date :

Mar 1, 2009

Actual Study Completion Date :

Mar 10, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ropinirole PR/XR	Drug: Ropinirole prolonged release/extended release(PR/XR) Subjects will take the investigational drug once daily at the same time each day, it is recommended that this is in the morning for optimal benefit. Investigational drug is taken for 52 weeks, starting on the next day of the Week 0 visit. One tablet of ropinirole PR/XR 2 mg tablets will be orally dosed as the initial dose. The dose will be titrated weekly by 2 mg/day, and increased to 8 mg/day in Week 4. From Week 5 up to 16, the dose will be increased at minimum intervals of one week between titration steps until sufficient efficacy is obtained, according to individual clinical response and tolerability (the dose may be titrated up to 16 mg/day). In Week 16 and further, treatment dose at Week 16 will be continuously administered up to Week 52. If insufficient efficacy is judged in a subject during treatment, or unable to maintain the dose due to adverse event, the treatment dose may be changed. The dose is down tapered according to the maintenance dose at Week 52 (or withdrawal).

Arm

Intervention/Treatment

Experimental: Ropinirole PR/XR

Drug: Ropinirole prolonged release/extended release(PR/XR)

Subjects will take the investigational drug once daily at the same time each day, it is recommended that this is in the morning for optimal benefit. Investigational drug is taken for 52 weeks, starting on the next day of the Week 0 visit. One tablet of ropinirole PR/XR 2 mg tablets will be orally dosed as the initial dose. The dose will be titrated weekly by 2 mg/day, and increased to 8 mg/day in Week 4. From Week 5 up to 16, the dose will be increased at minimum intervals of one week between titration steps until sufficient efficacy is obtained, according to individual clinical response and tolerability (the dose may be titrated up to 16 mg/day). In Week 16 and further, treatment dose at Week 16 will be continuously administered up to Week 52. If insufficient efficacy is judged in a subject during treatment, or unable to maintain the dose due to adverse event, the treatment dose may be changed. The dose is down tapered according to the maintenance dose at Week 52 (or withdrawal).

Outcome Measures

Primary Outcome Measures

Food Effects on Cmax and Cmin of SKF101468 (Ropinirole) and Its Metabolites [Weeks 5-16]
The dose of SKF101468 and its metabolites was normalized to 1 mg. Blood sampling at steady state up to 24 hours post dose after receiving the maintenance dose was conducted. In order to investigate the effect of a meal on pharmacokinetics, blood was sampled twice (after a standard morning meal and at fasted state) from identical participants. Cmax: maximum concentration, Cmin: trough plasma concentration.
Food Effects on AUC0-24 of SKF101468 (Ropinirole) and Its Metabolites [Weeks 5-16]
The dose of SKF101468 and its metabolites was normalized to 1 mg. Blood sampling at steady state up to 24 hours (hr) post dose after receiving the maintenance dose was conducted. In order to investigate the effect of a meal on pharmacokinetics, blood was sampled twice (after a standard morning meal and at fasted state) from identical participants. AUC0-24: area under the drug concentration 24 hr curve.
Food Effects on Tmax of SKF101468 (Ropinirole) and Its Metabolites [Weeks 5-16]
The dose of SKF101468 and its metabolites was normalized to 1 mg. Blood sampling at steady state up to 24 hours post dose after receiving the maintenance dose was conducted. In order to investigate the effect of a meal on pharmacokinetics, blood was sampled twice (after a standard morning meal and at fasted state) from identical participants. Tmax: time of maximum concentration. Data are presented as the median difference between fed and fasted states for ropinirole and each metabolite.
Plasma Trough Concentrations of SKF101468 (Ropinirole) and Its Metabolites [Weeks 1-16]
Blood sampling in the fixed titration phase will be performed at 24 hour post dose of the last dose of 2, 4, and 8 mg (immediately before the morning dose). Blood sampling in the maintenance dose phase will be performed at 24 hour post dose of 10 mg or more for one week or longer (immediately before the morning dose), as sampling needs to be conducted at steady state.

Secondary Outcome Measures

Total Score in the Japanese UPDRS Part III [Weeks 0-52]
The Unified Parkinson's Disease Rating Scale (UPDRS) assesses the status of Parkinson's Disease (PD) patients objectively. The Japanese UPDRS Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per each item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms.
Change From Baseline in the Japanese UPDRS Part III [Baseline (Week 0) and Weeks 1-52]
The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per each item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms.
Percent Change From Baseline in the Japanese UPDRS Part III [Baseline (Week 0) and Weeks 1-52]
The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per each item. A maximum total score is 108 points.The higher score indicates more severe PD symptoms.
Percentage of Responders of the Total Score in the Japanese UPDRS Total Score in Part III [Baseline (Week 0) and Weeks 1-52]
A responder is defined as a participant with a 30% or more reduction at baseline. The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per each item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms.
Total Score in the Japanese UPDRS Part I [Weeks 0-52]
The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part I assesses mentation, behavior, and mood on 4 items. Participants receive a score of 0-4 points per each item. The maximum total score is 16 points. A higher score indicates more severe mental symptoms.
Change From Baseline in the Japanese UPDRS Part I [Baseline (Week 0) and Weeks 1-52]
The UPDRS (Unified Parkinson's Disease Rating Scale) assesses the status of PD patients objectively. The Japanese UPDRS Part I assesses mentation, behavior, and mood on 4 items. Participants receive a score of 0-4 points per each item. The maximum total score is 16 points. A higher score indicates more severe mental symptoms.
Percent Change From Baseline in the Japanese UPDRS Part I [Baseline (Week 0) and Weeks 1-52]
The UPDRS (Unified Parkinson's Disease Rating Scale) assesses the status of PD patients objectively. The Japanese UPDRS Part I assesses mentation, behavior, and mood on 4 items. Participants receive a score of 0-4 points per each item. The maximum total score is 16 points. A higher score indicates more severe mental symptoms.
Total Score in the Japanese UPDRS Part II [Weeks 0-52]
The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per each item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms.
Change From Baseline in the Japanese UPDRS Part II [Baseline (Week 0) and Weeks 1-52]
The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per each item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms.
Percent Change From Baseline in the Japanese UPDRS Part II [Baseline (Week 0) and Weeks 1-52]
The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per each item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms.
Total Score in the Japanese UPDRS Part IV [Baseline (Week 0) and Weeks 0-52]
The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per each item depending on the item. The maximum total score is 23 points. A higher score indicates more severe symptoms of complications.
Change From Baseline in the Japanese UPDRS Part IV [Baseline (Week 0) and Weeks 1-52]
The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per each item depending on the item. The maximum total score is 23 points. A higher score indicates more severe symptoms of complications.
Percent Change From Baseline in the Japanese UPDRS Part IV [Baseline (Week 0) and Weeks 1-52]
The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per each item depending on the item. The maximum total score is 23 points. A higher score indicates more severe symptoms of complications.
Summary of the Modified Hoehn & Yahr Criteria Stages [Screening-Week 52]
Hoehn & Yahr criteria were measured on an 8-point scale. 0: No signs of disease, 1: Unilateral disease, 1.5: Unilateral plus axial involvement, 2: Bilateral disease, 2.5: Mild bilateral disease, 3: Mild to moderate bilateral disease. No subjects evaluated had a score of 4 (severe disability) or 5 (wheelchair bound or bedridden unless aided).
Number of Participants Scored as Responders on the Clinician's Global Impression (CGI) Scale [Weeks 1-52]
CGI is measured on a 7-point scale. 1: Very much improved, 2: Much Improved, 3: Minimally improved, 4: No change, 5: Minimally worse, 6: Much worse, 7: Very much worse. Responders are defined as those participants scored as "very much improved" or "much improved."
Percentage of Participants Who Remained in the Study on the Indicated Days [Days 0-364]
The percentage of participants remaining in the study was examined using the Kaplan-Meier method, in which a premature discontinuation will be considered as an event.
Change From Baseline in Albumin, Total Protein, and Hemoglobin at Weeks 16 and 52 [Baseline (Screening) and Weeks 16 and 52]
Change from baseline was calculated as the Week 16 and 52 values minus the baseline values.
Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Weeks 16 and 52 [Baseline (Screening) and Weeks 16 and 52]
Change from baseline was calculated as the Week 16 and 52 values minus the baseline values.
Change From Baseline in Total Bilirubin, Blood Urea Nitrogen, and Creatinine at Weeks 16 and 52 [Baseline (Screening) and Weeks 16 and 52]
Change from baseline was calculated as the Week 16 and 52 values minus the baseline values.
Change From Baseline in Blood Urea Nitrogen, Cholesterol, Chloride, Potassium, and Sodium at Weeks 16 and 52 [Baseline (Screening) and Weeks 16 and 52]
Change from baseline was calculated as the Week 16 and 52 values minus the baseline values.
Change From Baseline in Prolactin at Weeks 16 and 52 [Baseline (Screening) and Weeks 16 and 52]
Change from baseline was calculated as the Week 16 and 52 values minus the baseline values.
Change From Baseline in Hematocrit at Weeks 16 and 52 [Baseline (Screening) and Weeks 16 and 52]
Change from baseline was calculated as the Week 16 and 52 values minus the baseline values.
Change From Baseline in Platelet Count and White Blood Cell Count at Weeks 16 and 52 [Baseline (Screening) and Weeks 16 and 52]
Change from baseline was calculated as the Week 16 and 52 values minus the baseline values.
Change From Baseline in Red Blood Cell Count at Weeks 16 and 52 [Baseline (Screening) and Weeks 16 and 52]
Change from baseline was calculated as the Week 16 and 52 values minus the baseline values.
Urinalysis Data [Screening, Week 16, and Week 52]
The number of participants with the indicated dipstick test values were measured. Dipstick test values: Neg Value, Trace, +1, +2, +3, +4. No participants had a score of +5.
Number of Participants With the Indicated Shift From Baseline in 12-Lead Electrocardiogram (ECG) Findings at Weeks 16 and 52 [Baseline (Screening) and Weeks 16 and 52]
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.
Change From Baseline in Supine and Standing Systolic and Diastolic Blood Pressure at Weeks 16 and 52 [Baseline (Screening) and Weeks 16 and 52]
Change from baseline was calculated as Week 16 and Week 52 values minus baseline values.
Change From Baseline in Supine and Standing Pulse Rate at Weeks 16 and 52 [Baseline (Screening) and Weeks 16 and 52]
Change from baseline was calculated as Week 16 and Week 52 values minus baseline values.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients who are diagnosed with PD with severity of the Modified Hoehn & Yahr staging at Stage I to III.
Age: 20 years or older (at the time of giving informed consent)
Gender: male and female
Both inpatient and outpatient status
Informed consent: Patients who are able to give informed written consent in person (i.e. patients who are capable of giving informed written consent on one's own)
Limited prior exposure to low or moderate doses of L-dopa (up to 3 months in total) or dopamine agonists (up to 6 months in total) provided treatment is discontinued for a minimum of 4 weeks prior to screening.

Exclusion Criteria:

Patients who present serious physical signs and symptoms other than those of the PD (e.g. cardiac/hepatic/renal disorder and haematopoietic disorder). The seriousness 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 symptomatic postural hypotension. (e.g. dizziness and syncope).
Patients who have had serious psychiatric symptoms (e.g. confusion, hallucination, delusion, abnormal behaviour, alcohol or drug dependence) during the past six months (26 weeks) (including symptoms caused by anti-Parkinson drugs).
Patients who have been treated with the following drugs at Week -4, and whose treatment regimen of the drug has been changed from Week -4 to Week 0.
Anticholinergic agents: trihexyphenidyl hydrochloride (e.g. Artane®), piroheptine hydrochloride (Trimol®), mazaticol hydrochloride (Pentona®), metixene hydrochloride (Cholinfall®), biperiden hydrochloride (Akineton®), profenamine (Parkin®)
amantadine hydrochloride (e.g. Symmetrel®)
droxidopa (Dops®)
citicoline (e.g. Nicholin®)
selegiline hydrochloride (FP®)
zonisamide
estrogen: estriol (e.g.Estriel®)
CYP1A2 inhibitors: Ciprofloxacin HCl (e.g. Ciproxan®, enoxacin and fluvoxamine)
Patients with severe dementia such as score 3 or 4 of the UPDRS Part I (Mentation, behaviour, and mood)
Female patients who are pregnant or lactating, who may be pregnant, or who plan for pregnancy during the study or within 30 days after the last dose of the study drug.
Patients with current history or complication of carcinoma or malignant tumour.
Patients who have history of drug allergy to ropinirole hydrochloride (HCl).
Patients who have received surgical treatment for PD in the past (e.g. pallidectomy, deep brain stimulation).
Patients who have been treated with any other investigational drug within 12weeks prior to the treatment phase.
Others whom the investigator (sub investigator) considers ineligible for the study.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	GSK Investigational Site	Aichi	Japan	455-8530
2	GSK Investigational Site	Aichi	Japan	460-0008
3	GSK Investigational Site	Chiba	Japan	279-0021
4	GSK Investigational Site	Ehime	Japan	791-0295
5	GSK Investigational Site	Hokkaido	Japan	070-0901
6	GSK Investigational Site	Iwate	Japan	020-0878
7	GSK Investigational Site	Kanagawa	Japan	251-0038
8	GSK Investigational Site	Kyoto	Japan	600-8811
9	GSK Investigational Site	Osaka	Japan	570-8507
10	GSK Investigational Site	Saitama	Japan	343-0032
11	GSK Investigational Site	Tokyo	Japan	113-8431
12	GSK Investigational Site	Tokyo	Japan	136-0075

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:

NCT00434304

Other Study ID Numbers:

ROP106064

First Posted:

Feb 13, 2007

Last Update Posted:

Sep 27, 2018

Last Verified:

Aug 1, 2018

Keywords provided by GlaxoSmithKline

Parkinson's Disease

Additional relevant MeSH terms:

Parkinson Disease

Ropinirole

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Period Title: Overall Study
STARTED	62
COMPLETED	42
NOT COMPLETED	20

Baseline Characteristics

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Overall Participants	62
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.2 (8.05)
Sex: Female, Male (Count of Participants)
Female	37 59.7%
Male	25 40.3%
Race/Ethnicity, Customized (participants) [Number]
Asian - Japanese Heritage	62 100%

Outcome Measures

1. Primary Outcome

Title	Food Effects on Cmax and Cmin of SKF101468 (Ropinirole) and Its Metabolites
Description	The dose of SKF101468 and its metabolites was normalized to 1 mg. Blood sampling at steady state up to 24 hours post dose after receiving the maintenance dose was conducted. In order to investigate the effect of a meal on pharmacokinetics, blood was sampled twice (after a standard morning meal and at fasted state) from identical participants. Cmax: maximum concentration, Cmin: trough plasma concentration.
Time Frame	Weeks 5-16

Outcome Measure Data

Analysis Population Description
Pharmacokinetic (PK) Population: participants who underwent blood sampling for PK research, excluding those who did not fulfill inclusion criteria and those who were considered to affect the evaluation of the PK research due to drug incompliance or other protocol violation.

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	10
SKF101468 (ropinirole), Cmax, fed	1563.784
SKF101468 (ropinirole), Cmax, fasted	1542.182
SKF101468 (ropinirole), Cmin, fed	728.404
SKF101468 (ropinirole), Cmin, fasted	725.103
SKF104557 (metabolite), Cmax, fed	1159.120
SKF104557 (metabolite), Cmax, fasted	1250.554
SKF104557 (metabolite), Cmin, fed	798.871
SKF104557 (metabolite), Cmin, fasted	786.097
SKF89124 (metabolite), Cmax, fed	55.282
SKF89124 (metabolite), Cmax, fasted	60.742
SKF89124 (metabolite), Cmin, fed	34.281
SKF89124 (metabolite), Cmin, fasted	34.599

2. Secondary Outcome

Title	Total Score in the Japanese UPDRS Part III
Description	The Unified Parkinson's Disease Rating Scale (UPDRS) assesses the status of Parkinson's Disease (PD) patients objectively. The Japanese UPDRS Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per each item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms.
Time Frame	Weeks 0-52

Outcome Measure Data

Analysis Population Description
Full Analysis Set (FAS): all participants who progressed to the treatment phase, excluding those who did not fulfill major registration criteria, those who had not received at least one dose of the investigational drug, and those whose measured data were not available after treatment initiation. Participants dropped out of the study each week.

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Week 0, n=62	22.4 (10.11)
Week 1, n=62	19.3 (9.38)
Week 2, n=60	16.8 (8.89)
Week 3, n=60	14.5 (8.57)
Week 4, n=58	13.0 (8.60)
Week 6, n=57	12.1 (8.47)
Week 8, n=56	11.1 (7.87)
Week 10, n=57	10.2 (7.84)
Week 12, n=56	10.1 (7.18)
Week 16, n=54	10.3 (6.98)
Final Assessment Point (Up to Week 16), n=62	11.1 (7.52)
Week 20, n=53	10.4 (7.20)
Week 24, n=51	10.6 (7.47)
Week 28, n=48	10.6 (7.69)
Week 32, n=47	10.7 (7.68)
Week 36, n=47	10.7 (7.35)
Week 40, n=45	11.0 (8.04)
Week 44, n=45	11.3 (9.30)
Week 48, n=44	10.2 (7.52)
Week 52, n=44	10.7 (7.73)

3. Secondary Outcome

Title	Change From Baseline in the Japanese UPDRS Part III
Description	The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per each item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms.
Time Frame	Baseline (Week 0) and Weeks 1-52

Outcome Measure Data

Analysis Population Description
FAS. Participants dropped out of the study each week.

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Week 1, n=62	-3.1 (4.21)
Week 2, n=60	-5.8 (5.18)
Week 3, n=60	-7.7 (6.67)
Week 4, n=58	-9.7 (6.77)
Week 6, n=57	-10.5 (7.31)
Week 8, n=56	-11.5 (7.95)
Week 10, n=57	-12.4 (7.57)
Week 12, n=56	-12.3 (7.47)
Week 16, n=54	-12.2 (8.10)
Final Assessment Point (Up to Week 16), n=62	-11.3 (8.21)
Week 20, n=53	-12.1 (8.65)
Week 24, n=51	-11.6 (8.21)
Week 28, n=48	-11.5 (9.04)
Week 32, n=47	-11.7 (8.27)
Week 36, n=47	-11.7 (8.37)
Week 40, n=45	-11.5 (8.26)
Week 44, n=45	-11.2 (9.12)
Week 48, n=44	-11.9 (8.57)
Week 52, n=44	-11.4 (8.55)

4. Secondary Outcome

Title	Percent Change From Baseline in the Japanese UPDRS Part III
Description	The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per each item. A maximum total score is 108 points.The higher score indicates more severe PD symptoms.
Time Frame	Baseline (Week 0) and Weeks 1-52

Outcome Measure Data

Analysis Population Description
FAS. Participants dropped out of the study each week.

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Week 1, n=62	-14.14 (17.734)
Week 2, n=60	-27.14 (23.525)
Week 3, n=60	-35.13 (28.125)
Week 4, n=58	-45.03 (24.055)
Week 6, n=57	-48.35 (26.605)
Week 8, n=56	-51.34 (30.203)
Week 10, n=57	-56.63 (26.249)
Week 12, n=56	-56.24 (23.382)
Week 16, n=54	-53.78 (28.309)
Final Assessment Point (Up to Week 16), n=62	-49.38 (32.041)
Week 20, n=53	-52.61 (32.017)
Week 24, n=51	-51.56 (28.676)
Week 28, n=48	-50.25 (30.813)
Week 32, n=47	-51.67 (26.037)
Week 36, n=47	-51.36 (27.300)
Week 40, n=45	-50.58 (25.887)
Week 44, n=45	-49.51 (32.903)
Week 48, n=44	-53.05 (28.456)
Week 52, n=44	-51.11 (31.617)

5. Secondary Outcome

Title	Percentage of Responders of the Total Score in the Japanese UPDRS Total Score in Part III
Description	A responder is defined as a participant with a 30% or more reduction at baseline. The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per each item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms.
Time Frame	Baseline (Week 0) and Weeks 1-52

Outcome Measure Data

Analysis Population Description
FAS. Participants dropped out of the study each week.

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Week 1, n=62	12.9
Week 2, n=60	38.3
Week 3, n=60	58.3
Week 4, n=58	70.7
Week 6, n=57	71.9
Week 8, n=56	82.1
Week 10, n=57	84.2
Week 12, n=56	89.3
Week 16, n=54	81.5
Final Assessment Point (Up to Week 16), n=62	75.8
Week 20, n=53	81.1
Week 24, n=51	78.4
Week 28, n=48	79.2
Week 32, n=47	76.6
Week 36, n=47	76.6
Week 40, n=45	77.8
Week 44, n=45	77.8
Week 48, n=44	81.8
Week 52, n=44	81.8

6. Secondary Outcome

Title	Total Score in the Japanese UPDRS Part I
Description	The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part I assesses mentation, behavior, and mood on 4 items. Participants receive a score of 0-4 points per each item. The maximum total score is 16 points. A higher score indicates more severe mental symptoms.
Time Frame	Weeks 0-52

Outcome Measure Data

Analysis Population Description
FAS. Participants dropped out of the study each week.

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Week 0, n=62	1.0 (1.36)
Week 1, n=62	0.7 (1.09)
Week 2, n=60	0.6 (0.96)
Week 3, n=60	0.5 (1.06)
Week 4, n=58	0.4 (1.06)
Week 6, n=57	0.5 (1.04)
Week 8, n=56	0.5 (1.10)
Week 10, n=57	0.6 (1.39)
Week 12, n=56	0.4 (1.07)
Week 16, n=54	0.4 (1.31)
Final Assessment Point (Up to Week 16), n=62	0.4 (1.30)
Week 20, n=53	0.3 (0.88)
Week 24, n=51	0.4 (0.87)
Week 28, n=48	0.3 (0.57)
Week 32, n=47	0.3 (0.61)
Week 36, n=47	0.4 (0.64)
Week 40, n=45	0.3 (0.58)
Week 44, n=45	0.3 (0.67)
Week 48, n=44	0.3 (0.73)
Week 52, n=44	0.3 (0.80)

7. Secondary Outcome

Title	Change From Baseline in the Japanese UPDRS Part I
Description	The UPDRS (Unified Parkinson's Disease Rating Scale) assesses the status of PD patients objectively. The Japanese UPDRS Part I assesses mentation, behavior, and mood on 4 items. Participants receive a score of 0-4 points per each item. The maximum total score is 16 points. A higher score indicates more severe mental symptoms.
Time Frame	Baseline (Week 0) and Weeks 1-52

Outcome Measure Data

Analysis Population Description
FAS. Participants dropped out of the study each week.

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Week 1, n=62	-0.3 (1.00)
Week 2, n=60	-0.5 (0.91)
Week 3, n=60	-0.5 (1.14)
Week 4, n=58	-0.5 (1.13)
Week 6, n=57	-0.5 (1.21)
Week 8, n=56	-0.5 (1.16)
Week 10, n=57	-0.3 (1.21)
Week 12, n=56	-0.5 (1.14)
Week 16, n=54	-0.6 (1.24)
Final Assessment Point (Up to Week 16), n=62	-0.5 (1.21)
Week 20, n=53	-0.5 (1.15)
Week 24, n=51	-0.5 (1.10)
Week 28, n=48	-0.5 (1.11)
Week 32, n=47	-0.5 (1.20)
Week 36, n=47	-0.4 (1.28)
Week 40, n=45	-0.4 (1.16)
Week 44, n=45	-0.4 (1.25)
Week 48, n=44	-0.4 (1.30)
Week 52, n=44	-0.4 (1.30)

8. Secondary Outcome

Title	Percent Change From Baseline in the Japanese UPDRS Part I
Description	The UPDRS (Unified Parkinson's Disease Rating Scale) assesses the status of PD patients objectively. The Japanese UPDRS Part I assesses mentation, behavior, and mood on 4 items. Participants receive a score of 0-4 points per each item. The maximum total score is 16 points. A higher score indicates more severe mental symptoms.
Time Frame	Baseline (Week 0) and Weeks 1-52

Outcome Measure Data

Analysis Population Description
FAS. Participants dropped out of the study each week.

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Week 1, n=30	-34.17 (48.460)
Week 2, n=29	-54.60 (46.269)
Week 3, n=29	-63.79 (49.815)
Week 4, n=28	-60.71 (49.735)
Week 6, n=27	-69.44 (48.205)
Week 8, n=27	-54.94 (59.524)
Week 10, n=27	-48.46 (66.105)
Week 12, n=26	-62.50 (67.956)
Week 16, n=24	-77.08 (48.358)
Final Assessment Point (Up to Week 16), n=30	-68.89 (52.838)
Week 20, n=23	-71.74 (51.354)
Week 24, n=22	-65.91 (44.089)
Week 28, n=20	-71.67 (50.466)
Week 32, n=19	-67.54 (71.465)
Week 36, n=19	-55.26 (66.447)
Week 40, n=17	-69.61 (55.664)
Week 44, n=17	-52.94 (69.531)
Week 48, n=16	-59.38 (71.224)
Week 52, n=16	-53.13 (71.807)

9. Secondary Outcome

Title	Total Score in the Japanese UPDRS Part II
Description	The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per each item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms.
Time Frame	Weeks 0-52

Outcome Measure Data

Analysis Population Description
FAS. Participants dropped out of the study each week.

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Week 0, n=62	8.2 (4.55)
Week 1, n=62	7.2 (4.41)
Week 2, n=60	6.3 (4.00)
Week 3, n=60	5.5 (3.82)
Week 4, n=58	4.8 (3.79)
Week 6, n=57	4.5 (3.76)
Week 8, n=56	4.0 (3.64)
Week 10, n=57	4.1 (3.95)
Week 12, n=56	4.2 (3.77)
Week 16, n=54	4.1 (3.50)
Final Assessment Point (Up to Week 16), n=62	4.3 (3.69)
Week 20, n=53	4.1 (3.57)
Week 24, n=51	3.7 (3.38)
Week 28, n=48	4.0 (3.79)
Week 32, n=47	3.9 (3.61)
Week 36, n=47	4.0 (3.73)
Week 40, n=45	4.1 (3.90)
Week 44, n=45	4.2 (4.14)
Week 48, n=44	3.8 (3.88)
Week 52, n=44	4.1 (4.13)

10. Primary Outcome

Title	Food Effects on AUC0-24 of SKF101468 (Ropinirole) and Its Metabolites
Description	The dose of SKF101468 and its metabolites was normalized to 1 mg. Blood sampling at steady state up to 24 hours (hr) post dose after receiving the maintenance dose was conducted. In order to investigate the effect of a meal on pharmacokinetics, blood was sampled twice (after a standard morning meal and at fasted state) from identical participants. AUC0-24: area under the drug concentration 24 hr curve.
Time Frame	Weeks 5-16

Outcome Measure Data

Analysis Population Description
PK Population

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	10
SKF101468 (ropinirole), fed	27206.103
SKF101468 (ropinirole), fasted	27191.804
SKF104557 (metabolite), fed	23090.150
SKF104557 (metabolite), fasted	24478.797
SKF89124 (metabolite), fed	1044.877
SKF89124 (metabolite), fasted	1092.635

11. Primary Outcome

Title	Food Effects on Tmax of SKF101468 (Ropinirole) and Its Metabolites
Description	The dose of SKF101468 and its metabolites was normalized to 1 mg. Blood sampling at steady state up to 24 hours post dose after receiving the maintenance dose was conducted. In order to investigate the effect of a meal on pharmacokinetics, blood was sampled twice (after a standard morning meal and at fasted state) from identical participants. Tmax: time of maximum concentration. Data are presented as the median difference between fed and fasted states for ropinirole and each metabolite.
Time Frame	Weeks 5-16

Outcome Measure Data

Analysis Population Description
PK Population

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	10
SKF101468 (ropinirole)	2.000
SKF104557 (metabolite)	3.983
SKF89124 (metabolite)	1.000

12. Primary Outcome

Title	Plasma Trough Concentrations of SKF101468 (Ropinirole) and Its Metabolites
Description	Blood sampling in the fixed titration phase will be performed at 24 hour post dose of the last dose of 2, 4, and 8 mg (immediately before the morning dose). Blood sampling in the maintenance dose phase will be performed at 24 hour post dose of 10 mg or more for one week or longer (immediately before the morning dose), as sampling needs to be conducted at steady state.
Time Frame	Weeks 1-16

Outcome Measure Data

Analysis Population Description
PK Population. Blood sampling was performed in all participants in the Fixed titration phase and Maintenance dose phase to measure trough concentration. The maintenance dose differs for individual participants.

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	61
SKF101468 (ropinirole), 2 mg, n=61	1804.87 (1757.062)
SKF101468 (ropinirole), 4 mg, n=58	3529.59 (1746.855)
SKF101468 (ropinirole), 6 mg, n=1	3820.20 (0.000)
SKF101468 (ropinirole), 8 mg, n=61	7598.90 (5512.105)
SKF101468 (ropinirole), 10 mg, n=17	9772.23 (3237.589)
SKF101468 (ropinirole), 12 mg, n=12	11971.49 (7211.987)
SKF101468 (ropinirole), 14 mg, n=9	12575.41 (5586.121)
SKF101468 (ropinirole), 16 mg, n=12	15467.01 (8292.375)
SKF104557 (metabolite), 2 mg, n=61	1564.52 (777.387)
SKF104557 (metabolite), 4 mg, n=58	3224.53 (1184.861)
SKF104557 (metabolite), 6 mg, n=1	4172.10 (0.000)
SKF104557 (metabolite), 8 mg, n=61	6353.30 (2173.457)
SKF104557 (metabolite), 10 mg, n=17	7944.70 (1887.958)
SKF104557 (metabolite), 12 mg, n=12	11814.28 (3917.886)
SKF104557 (metabolite), 14 mg, n=9	11579.79 (4279.464)
SKF104557 (metabolite), 16 mg, n=12	12753.83 (2527.639)
SKF89124 (metabolite), 2 mg, n=61	66.14 (39.824)
SKF89124 (metabolite), 4 mg, n=58	139.84 (56.099)
SKF89124 (metabolite), 6 mg, n=1	157.40 (0.000)
SKF89124 (metabolite), 8 mg, n=61	281.36 (120.381)
SKF89124 (metabolite), 10 mg, n=17	318.82 (83.774)
SKF89124 (metabolite), 12 mg, n=12	479.36 (189.388)
SKF89124 (metabolite), 14 mg, n=9	564.57 (286.257)
SKF89124 (metabolite), 16 mg, n=12	628.76 (271.495)

13. Secondary Outcome

Title	Change From Baseline in the Japanese UPDRS Part II
Description	The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per each item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms.
Time Frame	Baseline (Week 0) and Weeks 1-52

Outcome Measure Data

Analysis Population Description
FAS. Participants dropped out of the study each week.

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Week 1, n=62	-1.0 (1.60)
Week 2, n=60	-1.9 (2.14)
Week 3, n=60	-2.6 (2.44)
Week 4, n=58	-3.4 (2.84)
Week 6, n=57	-3.7 (2.74)
Week 8, n=56	-4.2 (3.09)
Week 10, n=57	-4.1 (3.16)
Week 12, n=56	-4.0 (3.20)
Week 16, n=54	-4.1 (3.28)
Final Assessment Point (Up to Week 16), n=62	-3.9 (3.22)
Week 20, n=53	-4.1 (3.50)
Week 24, n=51	-4.4 (3.48)
Week 28, n=48	-4.0 (3.75)
Week 32, n=47	-4.2 (3.66)
Week 36, n=47	-4.1 (3.80)
Week 40, n=45	-3.9 (3.98)
Week 44, n=45	-3.8 (3.84)
Week 48, n=44	-4.0 (3.96)
Week 52, n=44	-3.7 (4.42)

14. Secondary Outcome

Title	Percent Change From Baseline in the Japanese UPDRS Part II
Description	The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per each item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms.
Time Frame	Baseline (Week 0) and Weeks 1-52

Outcome Measure Data

Analysis Population Description
FAS. Participants dropped out of the study each week.

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Week 1, n=60	-11.01 (20.504)
Week 2, n=58	-23.04 (26.252)
Week 3, n=58	-33.09 (26.531)
Week 4, n=56	-44.30 (28.348)
Week 6, n=55	-48.89 (28.058)
Week 8, n=54	-53.88 (29.274)
Week 10, n=55	-52.52 (35.133)
Week 12, n=54	-51.51 (31.572)
Week 16, n=52	-50.78 (35.826)
Final Assessment Point (Up to Week 16), n=60	-49.03 (35.664)
Week 20, n=51	-50.10 (35.694)
Week 24, n=49	-54.29 (31.096)
Week 28, n=46	-51.15 (35.620)
Week 32, n=45	-50.91 (37.745)
Week 36, n=45	-51.05 (35.493)
Week 40, n=43	-48.31 (41.477)
Week 44, n=43	-47.48 (40.194)
Week 48, n=42	-49.28 (38.285)
Week 52, n=42	-41.48 (48.287)

15. Secondary Outcome

Title	Total Score in the Japanese UPDRS Part IV
Description	The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per each item depending on the item. The maximum total score is 23 points. A higher score indicates more severe symptoms of complications.
Time Frame	Baseline (Week 0) and Weeks 0-52

Outcome Measure Data

Analysis Population Description
FAS. Participants dropped out of the study each week.

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Week 0, n=62	0.4 (0.58)
Week 1, n=62	0.6 (0.71)
Week 2, n=60	0.8 (0.82)
Week 3, n=60	0.7 (0.78)
Week 4, n=58	0.7 (0.82)
Week 6, n=57	0.7 (0.78)
Week 8, n=56	0.5 (0.63)
Week 10, n=57	0.5 (0.68)
Week 12, n=56	0.5 (0.66)
Week 16, n=54	0.6 (0.63)
Final Assessment Point (Up to Week 16), n=62	0.6 (0.66)
Week 20, n=53	0.6 (0.71)
Week 24, n=51	0.5 (0.64)
Week 28, n=48	0.6 (0.70)
Week 32, n=47	0.5 (0.62)
Week 36, n=47	0.6 (0.62)
Week 40, n=45	0.4 (0.58)
Week 44, n=45	0.5 (0.59)
Week 48, n=44	0.5 (0.59)
Week 52, n=44	0.5 (0.63)

16. Secondary Outcome

Title	Change From Baseline in the Japanese UPDRS Part IV
Description	The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per each item depending on the item. The maximum total score is 23 points. A higher score indicates more severe symptoms of complications.
Time Frame	Baseline (Week 0) and Weeks 1-52

Outcome Measure Data

Analysis Population Description
FAS. Participants dropped out of the study each week.

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Week 1, n=62	0.2 (0.64)
Week 2, n=60	0.4 (0.74)
Week 3, n=60	0.3 (0.74)
Week 4, n=58	0.3 (0.78)
Week 6, n=57	0.3 (0.83)
Week 8, n=56	0.2 (0.74)
Week 10, n=57	0.2 (0.70)
Week 12, n=56	0.2 (0.72)
Week 16, n=54	0.2 (0.63)
Final Assessment Point (Up to Week 16), n=62	0.2 (0.66)
Week 20, n=53	0.3 (0.67)
Week 24, n=51	0.2 (0.68)
Week 28, n=48	0.3 (0.75)
Week 32, n=47	0.2 (0.70)
Week 36, n=47	0.3 (0.71)
Week 40, n=45	0.1 (0.66)
Week 44, n=45	0.2 (0.63)
Week 48, n=44	0.3 (0.72)
Week 52, n=44	0.2 (0.74)

17. Secondary Outcome

Title	Percent Change From Baseline in the Japanese UPDRS Part IV
Description	The UPDRS assesses the status of PD patients objectively. The Japanese UPDRS Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per each item depending on the item. The maximum total score is 23 points. A higher score indicates more severe symptoms of complications.
Time Frame	Baseline (Week 0) and Weeks 1-52

Outcome Measure Data

Analysis Population Description
FAS. Participants dropped out of the study each week.

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Week 1, n=21	-2.38 (64.180)
Week 2, n=20	17.50 (71.221)
Week 3, n=19	10.53 (79.196)
Week 4, n=19	7.89 (75.024)
Week 6, n=18	-5.56 (72.536)
Week 8, n=17	-35.29 (60.634)
Week 10, n=18	-16.67 (70.711)
Week 12, n=17	-14.71 (70.189)
Week 16, n=16	-15.63 (50.724)
Final Assessment Point (Up to Week 16), n=21	-16.67 (48.305)
Week 20, n=15	-6.67 (79.881)
Week 24, n=14	-25.00 (58.012)
Week 28, n=13	-23.08 (59.914)
Week 32, n=13	-34.62 (62.532)
Week 36, n=13	-26.92 (72.501)
Week 40, n=12	-41.67 (79.296)
Week 44, n=12	-25.00 (75.378)
Week 48, n=12	-41.67 (66.856)
Week 52, n=12	-41.67 (51.493)

18. Secondary Outcome

Title	Summary of the Modified Hoehn & Yahr Criteria Stages
Description	Hoehn & Yahr criteria were measured on an 8-point scale. 0: No signs of disease, 1: Unilateral disease, 1.5: Unilateral plus axial involvement, 2: Bilateral disease, 2.5: Mild bilateral disease, 3: Mild to moderate bilateral disease. No subjects evaluated had a score of 4 (severe disability) or 5 (wheelchair bound or bedridden unless aided).
Time Frame	Screening-Week 52

Outcome Measure Data

Analysis Population Description
FAS. Participants dropped out of the study each week.

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Screening, Stage 0	0
Screening, Stage 1	7
Screening, Stage 1.5	7
Screening, Stage 2	18
Screening, Stage 2.5	12
Screening, Stage 3	18
Week 0, Stage 0	0
Week 0, Stage 1	6
Week 0, Stage 1.5	5
Week 0, Stage 2	23
Week 0, Stage 2.5	12
Week 0, Stage 3	16
Week 1, Stage 0	0
Week 1, Stage 1	8
Week 1, Stage 1.5	4
Week 1, Stage 2	24
Week 1, Stage 2.5	12
Week 1, Stage 3	14
Week 2, Stage 0	1
Week 2, Stage 1	8
Week 2, Stage 1.5	5
Week 2, Stage 2	22
Week 2, Stage 2.5	12
Week 2, Stage 3	12
Week 3, Stage 0	0
Week 3, Stage 1	12
Week 3, Stage 1.5	3
Week 3, Stage 2	26
Week 3, Stage 2.5	8
Week 3, Stage 3	11
Week 4, Stage 0	0
Week 4, Stage 1	12
Week 4, Stage 1.5	5
Week 4, Stage 2	26
Week 4, Stage 2.5	7
Week 4, Stage 3	8
Week 6, Stage 0	1
Week 6, Stage 1	17
Week 6, Stage 1.5	4
Week 6, Stage 2	23
Week 6, Stage 2.5	3
Week 6, Stage 3	9
Week 8, Stage 0	1
Week 8, Stage 1	18
Week 8, Stage 1.5	5
Week 8, Stage 2	21
Week 8, Stage 2.5	7
Week 8, Stage 3	4
Week 10, Stage 0	3
Week 10, Stage 1	19
Week 10, Stage 1.5	7
Week 10, Stage 2	21
Week 10, Stage 2.5	2
Week 10, Stage 3	5
Week 12, Stage 0	3
Week 12, Stage 1	18
Week 12, Stage 1.5	8
Week 12, Stage 2	17
Week 12, Stage 2.5	5
Week 12, Stage 3	5
Week 16, Stage 0	3
Week 16, Stage 1	16
Week 16, Stage 1.5	6
Week 16, Stage 2	20
Week 16, Stage 2.5	4
Week 16, Stage 3	5
Final Assessment Point (Up to Week 16), Stage 0	3
Final Assessment Point (Up to Week 16), Stage 1	18
Final Assessment Point (Up to Week 16), Stage 1.5	6
Final Assessment Point (Up to Week 16), Stage 2	23
Final Assessment Point (Up to Week 16), Stage 2.5	5
Final Assessment Point (Up to Week 16), Stage 3	7
Week 20, Stage 0	4
Week 20, Stage 1	16
Week 20, Stage 1.5	3
Week 20, Stage 2	20
Week 20, Stage 2.5	3
Week 20, Stage 3	7
Week 24, Stage 0	3
Week 24, Stage 1	14
Week 24, Stage 1.5	3
Week 24, Stage 2	22
Week 24, Stage 2.5	4
Week 24, Stage 3	5
Week 28, Stage 0	2
Week 28, Stage 1	14
Week 28, Stage 1.5	4
Week 28, Stage 2	17
Week 28, Stage 2.5	5
Week 28, Stage 3	6
Week 32, Stage 0	2
Week 32, Stage 1	14
Week 32, Stage 1.5	2
Week 32, Stage 2	19
Week 32, Stage 2.5	5
Week 32, Stage 3	5
Week 36, Stage 0	2
Week 36, Stage 1	13
Week 36, Stage 1.5	2
Week 36, Stage 2	19
Week 36, Stage 2.5	6
Week 36, Stage 3	5
Week 40, Stage 0	2
Week 40, Stage 1	12
Week 40, Stage 1.5	2
Week 40, Stage 2	18
Week 40, Stage 2.5	7
Week 40, Stage 3	4
Week 44, Stage 0	2
Week 44, Stage 1	16
Week 44, Stage 1.5	2
Week 44, Stage 2	14
Week 44, Stage 2.5	5
Week 44, Stage 3	6
Week 48, Stage 0	1
Week 48, Stage 1	16
Week 48, Stage 1.5	1
Week 48, Stage 2	16
Week 48, Stage 2.5	4
Week 48, Stage 3	6
Week 52, Stage 0	1
Week 52, Stage 1	15
Week 52, Stage 1.5	2
Week 52, Stage 2	16
Week 52, Stage 2.5	5
Week 52, Stage 3	5

19. Secondary Outcome

Title	Number of Participants Scored as Responders on the Clinician's Global Impression (CGI) Scale
Description	CGI is measured on a 7-point scale. 1: Very much improved, 2: Much Improved, 3: Minimally improved, 4: No change, 5: Minimally worse, 6: Much worse, 7: Very much worse. Responders are defined as those participants scored as "very much improved" or "much improved."
Time Frame	Weeks 1-52

Outcome Measure Data

Analysis Population Description
FAS. Participants dropped out of the study each week.

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Week 1, n=62	8 12.9%
Week 2, n=60	16 25.8%
Week 3, n=60	25 40.3%
Week 4, n=58	39 62.9%
Week 6, n=57	40 64.5%
Week 8, n=56	45 72.6%
Week 10, n=57	47 75.8%
Week 12, n=56	48 77.4%
Week 16, n=54	41 66.1%
Final Assessment Point (Up to Week 16), n=62	44 71%
Week 20, n=53	43 69.4%
Week 24, n=51	40 64.5%
Week 28, n=48	38 61.3%
Week 32, n=47	35 56.5%
Week 36, n=47	35 56.5%
Week 40, n=45	33 53.2%
Week 44, n=45	35 56.5%
Week 48, n=44	37 59.7%
Week 52, n=44	35 56.5%

20. Secondary Outcome

Title	Percentage of Participants Who Remained in the Study on the Indicated Days
Description	The percentage of participants remaining in the study was examined using the Kaplan-Meier method, in which a premature discontinuation will be considered as an event.
Time Frame	Days 0-364

Outcome Measure Data

Analysis Population Description
FAS. Participants dropped out of the study each week.

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Day 0	100 161.3%
Day 10	98 158.1%
Day 14	97 156.5%
Day 21	94 151.6%
Day 28	92 148.4%
Day 70	90 145.2%
Day 84	89 143.5%
Day 96	87 140.3%
Day 112	85 137.1%
Day 140	84 135.5%
Day 168	82 132.3%
Day 175	79 127.4%
Day 183	77 124.2%
Day 196	76 122.6%
Day 239	74 119.4%
Day 252	73 117.7%
Day 315	71 114.5%
Day 359	69 111.3%
Day 364	67 108.1%

21. Secondary Outcome

Title	Change From Baseline in Albumin, Total Protein, and Hemoglobin at Weeks 16 and 52
Description	Change from baseline was calculated as the Week 16 and 52 values minus the baseline values.
Time Frame	Baseline (Screening) and Weeks 16 and 52

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received at least one dose of study medication. Week 16 (Last observation carried forward [LOCF]) = 62 participants; Week 52 (Observed case [OC]) = 44 participants

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Albumin, Week 16	-0.66 (1.983)
Albumin, Week 52	-1.68 (2.428)
Total Protein, Week 16	-1.71 (3.761)
Total Protein, Week 52	-2.32 (3.665)
Hemoglobin, Week 16	-4.44 (9.557)
Hemoglobin, Week 52	-4.00 (11.477)

22. Secondary Outcome

Title	Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Weeks 16 and 52
Description	Change from baseline was calculated as the Week 16 and 52 values minus the baseline values.
Time Frame	Baseline (Screening) and Weeks 16 and 52

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received at least one dose of study medication. Week 16 (Last observation carried forward [LOCF]) = 62 participants; Week 52 (Observed case [OC]) = 44 participants

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Alkaline Phosphatase, Week 16	16.5 (47.25)
Alkaline Phosphatase, Week 52	2.5 (37.78)
Alanine Amino Transferase, Week 16	1.1 (9.34)
Alanine Amino Transferase, Week 52	2.3 (13.34)
Aspartate Amino Transferase, Week 16	0.3 (6.71)
Aspartate Amino Transferase, Week 52	2.0 (9.14)
Creatine Kinase, Week 16	5.7 (117.47)
Creatine Kinase, Week 52	44.0 (142.26)
Gamma Glutamyl transferase, Week 16	-0.2 (21.60)
Gamma Glutamyl transferase, Week 52	-3.6 (28.47)
Lactate Dehydrogenase, Week 16	-2.9 (28.59)
Lactate Dehydrogenase, Week 52	8.7 (34.25)

23. Secondary Outcome

Title	Change From Baseline in Total Bilirubin, Blood Urea Nitrogen, and Creatinine at Weeks 16 and 52
Description	Change from baseline was calculated as the Week 16 and 52 values minus the baseline values.
Time Frame	Baseline (Screening) and Weeks 16 and 52

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received at least one dose of study medication. Week 16 (Last observation carried forward [LOCF]) = 62 participants; Week 52 (Observed case [OC]) = 44 participants

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Total Bilirubin, Week 16	0.19 (3.806)
Total Bilirubin, Week 52	0.12 (2.429)
Creatinine, Week 16	2.281 (6.780)
Creatinine, Week 52	1.266 (7.763)

24. Secondary Outcome

Title	Change From Baseline in Blood Urea Nitrogen, Cholesterol, Chloride, Potassium, and Sodium at Weeks 16 and 52
Description	Change from baseline was calculated as the Week 16 and 52 values minus the baseline values.
Time Frame	Baseline (Screening) and Weeks 16 and 52

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received at least one dose of study medication. Week 16 (Last observation carried forward [LOCF]) = 62 participants; Week 52 (Observed case [OC]) = 44 participants

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Blood Urea Nitrogen, Week 16	0.02 (1.448)
Blood Urea Nitrogen, Week 52	0.19 (1.512)
Cholesterol, Week 16	-0.3 (0.65)
Cholesterol, Week 52	-0.3 (0.59)
Chloride, Week 16	-0.1 (2.62)
Chloride, Week 52	0.4 (2.13)
Potassium, Week 16	-0.01 (0.334)
Potassium, Week 52	-0.03 (0.378)
Sodium, Week 16	-0.1 (2.46)
Sodium, Week 52	-0.1 (1.92)

25. Secondary Outcome

Title	Change From Baseline in Prolactin at Weeks 16 and 52
Description	Change from baseline was calculated as the Week 16 and 52 values minus the baseline values.
Time Frame	Baseline (Screening) and Weeks 16 and 52

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received at least one dose of study medication. Week 16 (Last observation carried forward [LOCF]) = 62 participants; Week 52 (Observed case [OC]) = 44 participants

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Week 16	-7.22 (7.132)
Week 52	-8.18 (2.495)

26. Secondary Outcome

Title	Change From Baseline in Hematocrit at Weeks 16 and 52
Description	Change from baseline was calculated as the Week 16 and 52 values minus the baseline values.
Time Frame	Baseline (Screening) and Weeks 16 and 52

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received at least one dose of study medication. Week 16 (Last observation carried forward [LOCF]) = 62 participants; Week 52 (Observed case [OC]) = 44 participants

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Week 16	-0.01 (0.028)
Week 52	-0.01 (0.028)

27. Secondary Outcome

Title	Change From Baseline in Platelet Count and White Blood Cell Count at Weeks 16 and 52
Description	Change from baseline was calculated as the Week 16 and 52 values minus the baseline values.
Time Frame	Baseline (Screening) and Weeks 16 and 52

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received at least one dose of study medication. Week 16 (Last observation carried forward [LOCF]) = 62 participants; Week 52 (Observed case [OC]) = 44 participants

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Platelet count, Week 16	-6.81 (31.618)
Platelet count, Week 52	-8.07 (44.229)
White Blood Cell Count, Week 16	-0.6 (1.30)
White Blood Cell Count, Week 52	-0.5 (1.10)

28. Secondary Outcome

Title	Change From Baseline in Red Blood Cell Count at Weeks 16 and 52
Description	Change from baseline was calculated as the Week 16 and 52 values minus the baseline values.
Time Frame	Baseline (Screening) and Weeks 16 and 52

Outcome Measure Data

Analysis Population Description
Safety Population: all participants who received at least one dose of study medication. Week 16 (Last observation carried forward [LOCF]) = 62 participants; Week 52 (Observed case [OC]) = 44 participants

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Week 16	-0.1 (0.26)
Week 52	-0.2 (0.27)

29. Secondary Outcome

Title	Urinalysis Data
Description	The number of participants with the indicated dipstick test values were measured. Dipstick test values: Neg Value, Trace, +1, +2, +3, +4. No participants had a score of +5.
Time Frame	Screening, Week 16, and Week 52

Outcome Measure Data

Analysis Population Description
Safety Population: Screening Week 16 (LOCF) = 62 participants; Week 52 (OC) = 44 participants

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Urine Occult Blood - Screening: Neg Value	52 83.9%
Urine Occult Blood - Screening: Trace	7 11.3%
Urine Occult Blood - Screening: +1	1 1.6%
Urine Occult Blood - Screening: +2	1 1.6%
Urine Occult Blood - Screening: +3	1 1.6%
Urine Occult Blood - Screening: +4	0 0%
Urine Occult Blood - Week 16: Neg Value	53 85.5%
Urine Occult Blood - Week 16: Trace	4 6.5%
Urine Occult Blood - Week 16: +1	5 8.1%
Urine Occult Blood - Week 16: +2	0 0%
Urine Occult Blood - Week 16: +3	0 0%
Urine Occult Blood - Week 16: +4	0 0%
Urine Occult Blood - Week 52: Neg Value	41 66.1%
Urine Occult Blood - Week 52: Trace	1 1.6%
Urine Occult Blood - Week 52: +1	2 3.2%
Urine Occult Blood - Week 52: +2	0 0%
Urine Occult Blood - Week 52: +3	0 0%
Urine Occult Blood - Week 52: +4	0 0%
Urine Glucose - Screening: Neg Value	57 91.9%
Urine Glucose - Screening: Trace	0 0%
Urine Glucose - Screening: +1	1 1.6%
Urine Glucose - Screening: +2	2 3.2%
Urine Glucose - Screening: +3	1 1.6%
Urine Glucose - Screening: +4	1 1.6%
Urine Glucose - Week 16: Neg Value	59 95.2%
Urine Glucose - Week 16: Trace	0 0%
Urine Glucose - Week 16: +1	2 3.2%
Urine Glucose - Week 16: +2	0 0%
Urine Glucose - Week 16: +3	0 0%
Urine Glucose - Week 16: +4	1 1.6%
Urine Glucose - Week 52: Neg Value	41 66.1%
Urine Glucose - Week 52: Trace	2 3.2%
Urine Glucose - Week 52: +1	0 0%
Urine Glucose - Week 52: +2	0 0%
Urine Glucose - Week 52: +3	0 0%
Urine Glucose - Week 52: +4	1 1.6%
Urine Protein - Screening: Neg Value	60 96.8%
Urine Protein - Screening: Trace	0 0%
Urine Protein - Screening: +1	2 3.2%
Urine Protein - Screening: +2	0 0%
Urine Protein - Screening: +3	0 0%
Urine Protein - Screening: +4	0 0%
Urine Protein - Week 16: Neg Value	55 88.7%
Urine Protein - Week 16: Trace	3 4.8%
Urine Protein - Week 16: +1	3 4.8%
Urine Protein - Week 16: +2	1 1.6%
Urine Protein - Week 16: +3	0 0%
Urine Protein - Week 16: +4	0 0%
Urine Protein - Week 52: Neg Value	43 69.4%
Urine Protein - Week 52: Trace	0 0%
Urine Protein - Week 52: +1	1 1.6%
Urine Protein - Week 52: +2	0 0%
Urine Protein - Week 52: +3	0 0%
Urine Protein - Week 52: +4	0 0%
Urine Urobilinogen - Screening: Neg Value	0 0%
Urine Urobilinogen - Screening: Trace	62 100%
Urine Urobilinogen - Screening: +1	0 0%
Urine Urobilinogen - Screening: +2	0 0%
Urine Urobilinogen - Screening: +3	0 0%
Urine Urobilinogen - Screening: +4	0 0%
Urine Urobilinogen - Week 16: Neg Value	0 0%
Urine Urobilinogen - Week 16: Trace	61 98.4%
Urine Urobilinogen - Week 16: +1	1 1.6%
Urine Urobilinogen - Week 16: +2	0 0%
Urine Urobilinogen - Week 16: +3	0 0%
Urine Urobilinogen - Week 16: +4	0 0%
Urine Urobilinogen - Week 52: Neg Value	0 0%
Urine Urobilinogen - Week 52: Trace	43 69.4%
Urine Urobilinogen - Week 52: +1	1 1.6%
Urine Urobilinogen - Week 52: +2	0 0%
Urine Urobilinogen - Week 52: +3	0 0%
Urine Urobilinogen - Week 52: +4	0 0%

30. Secondary Outcome

Title	Number of Participants With the Indicated Shift From Baseline in 12-Lead Electrocardiogram (ECG) Findings at Weeks 16 and 52
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 (Screening) and Weeks 16 and 52

Outcome Measure Data

Analysis Population Description
Safety Population: Week 16 (LOCF) = 62 participants; Week 52 (OC) = 44 participants

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Baseline: N; Week 16: N	32 51.6%
Baseline: N; Week 16: ANCS	10 16.1%
Baseline: N; Week 16: ACS	0 0%
Baseline: ANCS; Week 16: N	5 8.1%
Baseline: ANCS; Week 16: ANCS	13 21%
Baseline: ANCS; Week 16: ACS	0 0%
Baseline: ACS; Week 16: N	0 0%
Baseline: ACS; Week 16: ANCS	0 0%
Baseline: ACS; Week 16: ACS	2 3.2%
Baseline: N; Week 52: N	26 41.9%
Baseline: N; Week 52: ANCS	3 4.8%
Baseline: N; Week 52: ACS	0 0%
Baseline: ANCS; Week 52: N	5 8.1%
Baseline: ANCS; Week 52: ANCS	9 14.5%
Baseline: ANCS; Week 52: ACS	0 0%
Baseline: ACS; Week 52: N	0 0%
Baseline: ACS; Week 52: ANCS	0 0%
Baseline: ACS; Week 52: ACS	1 1.6%

31. Secondary Outcome

Title	Change From Baseline in Supine and Standing Systolic and Diastolic Blood Pressure at Weeks 16 and 52
Description	Change from baseline was calculated as Week 16 and Week 52 values minus baseline values.
Time Frame	Baseline (Screening) and Weeks 16 and 52

Outcome Measure Data

Analysis Population Description
Safety Population: Week 16 (LOCF) = 62 participants; Week 52 (OC) = 44 participants

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Supine Systolic BP - Week 16	-0.0 (20.54)
Supine Systolic BP - Week 52	-1.2 (22.84)
Supine Diastolic BP - Week 16	0.6 (11.57)
Supine Diastolic BP - Week 52	-1.2 (12.06)
Standing Systolic BP - Week 16	-0.7 (19.77)
Standing Systolic BP - Week 52	0.0 (19.08)
Standing Diastolic BP - Week 16	-0.7 (12.93)
Standing Diastolic BP - Week 52	2.1 (12.17)

32. Secondary Outcome

Title	Change From Baseline in Supine and Standing Pulse Rate at Weeks 16 and 52
Description	Change from baseline was calculated as Week 16 and Week 52 values minus baseline values.
Time Frame	Baseline (Screening) and Weeks 16 and 52

Outcome Measure Data

Analysis Population Description
Safety Population: Week 16 (LOCF) = 62 participants; Week 52 (OC) = 44 participants

Arm/Group Title	Ropinirole PR/XR
Arm/Group Description	Treatment Phase: Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 milligrams (mg) as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52. Taper phase: the dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
Measure Participants	62
Supine Heart Rate - Week 16	0.2 (9.13)
Supine Heart Rate - Week 52	-2.3 (11.22)
Standing Heart Rate - Week 16	0.2 (10.32)
Standing Heart Rate - Week 52	0.0 (9.43)

Adverse Events

	Ropinirole PR/XR (Treatment Phase)		Ropinirole PR/XR (Taper Phase)
Time Frame
Adverse Event Reporting Description

Arm/Group Title	Ropinirole PR/XR (Treatment Phase)		Ropinirole PR/XR (Taper Phase)
Arm/Group Description	Fixed titration phase (4 weeks): one tablet of ropinirole PR/XR 2 mg as the initial dose. The dose was titrated weekly by 2 mg/day and was increased to 8 mg/day in Week 4; Flexible titration and maintenance dose phases (48 weeks): from Week 5 up to Week 16, the dose was increased at minimum intervals of 1 week between titration steps (up to 16 mg/day). From Week 16 onward, treatment dose was continuously administered up to Week 52.		The dose was tapered over 2 to 3 weeks according to the maintenance dose at completion of the Treatment Phase (or withdrawal)
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ropinirole PR/XR (Treatment Phase)		Ropinirole PR/XR (Taper Phase)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/62 (8.1%)		1/62 (1.6%)
Gastrointestinal disorders
Intestinal obstruction	1/62 (1.6%)		0/62 (0%)
Immune system disorders
Anti-neutrophil cytoplasmic antibody positive vasculitis	1/62 (1.6%)		0/62 (0%)
Infections and infestations
Pneumonia	0/62 (0%)		1/62 (1.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian neoplasm	1/62 (1.6%)		0/62 (0%)
Small intestine carcinoma	1/62 (1.6%)		0/62 (0%)
Nervous system disorders
Cerebral infarction	1/62 (1.6%)		0/62 (0%)
Renal and urinary disorders
Glomerulonephritis rapidly progressive	1/62 (1.6%)		0/62 (0%)
Other (Not Including Serious) Adverse Events
	Ropinirole PR/XR (Treatment Phase)		Ropinirole PR/XR (Taper Phase)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/62 (82.3%)		0/62 (0%)
Gastrointestinal disorders
Nausea	18/62 (29%)		0/62 (0%)
Constipation	16/62 (25.8%)		0/62 (0%)
Vomiting	5/62 (8.1%)		0/62 (0%)
Stomach discomfort	4/62 (6.5%)		0/62 (0%)
General disorders
Edema peripheral	4/62 (6.5%)		0/62 (0%)
Infections and infestations
Nasopharyngitis	12/62 (19.4%)		0/62 (0%)
Bronchitis	4/62 (6.5%)		0/62 (0%)
Musculoskeletal and connective tissue disorders
Back pain	4/62 (6.5%)		0/62 (0%)
Nervous system disorders
Somnolence	25/62 (40.3%)		0/62 (0%)
Dizziness	5/62 (8.1%)		0/62 (0%)
Headache	5/62 (8.1%)		0/62 (0%)
Psychiatric disorders
Hallucination	13/62 (21%)		0/62 (0%)

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

Results Point of Contact

Name/Title	GSK Response Center
Organization	GlaxoSmithKline
Phone	866-435-7343
Email

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT00434304

Other Study ID Numbers:

ROP106064

First Posted:

Feb 13, 2007

Last Update Posted:

Sep 27, 2018

Last Verified:

Aug 1, 2018

Clinical Evaluation of Ropinirole PR/XR Tablets in Monotherapy for Parkinson's Disease (PD)

Study Details

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Adverse Events

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