Trial Outcomes & Findings for REQUIP (Ropinirole Hydrochloride) IR Long-Term Phase 4 Study (NCT NCT00485069)

Results Overview

The Japanese UPDRS assesses the status of Parkinson's Disease (PD) patients objectively. Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms. "On" state is where PD symptoms are well controlled by the drug. Participants with "off" state at baseline or without post-baseline data were not included in the ROP+L-dopa group at FAP. These participants as well as one with "off" state at Week 52 and those prematurely withdrawn were not included at Week 52.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

123 participants

Primary outcome timeframe

Baseline, Week 52, and FAP (up to Week 52)

Results posted on

2010-12-15

Participant Flow

52 weeks of Treatment Phase, consisting of 4 weeks of Fixed Titration Phase and 48 weeks of Flexible Titration and Maintenance Phase, was started after 1 to 4 weeks of Screening Phase. Although the results are presented by participants with and without L-dopa, this study was a single-arm design, and L-dopa was not the investigational product.

Participant milestones

Participant milestones
Measure	ROP+L-Dopa Participants received ropinirole hydrochloride (ROP) tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 milligrams (mg)/day and was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals of at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day and was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals of at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Overall Study STARTED	65	58
Overall Study COMPLETED	47	46
Overall Study NOT COMPLETED	18	12

Reasons for withdrawal

Reasons for withdrawal
Measure	ROP+L-Dopa Participants received ropinirole hydrochloride (ROP) tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 milligrams (mg)/day and was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals of at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day and was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals of at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Overall Study Adverse Event	10	4
Overall Study Lack of Efficacy	2	1
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	6	6

Baseline Characteristics

REQUIP (Ropinirole Hydrochloride) IR Long-Term Phase 4 Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ROP+L-Dopa n=65 Participants Participants received ropinirole hydrochloride (ROP) tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 milligrams (mg)/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride n=58 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.	Total n=123 Participants Total of all reporting groups
Age Continuous	66.0 Years STANDARD_DEVIATION 7.94 • n=5 Participants	65.5 Years STANDARD_DEVIATION 7.18 • n=7 Participants	65.8 Years STANDARD_DEVIATION 7.56 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	31 Participants n=7 Participants	58 Participants n=5 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	27 Participants n=7 Participants	65 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	65 participants n=5 Participants	58 participants n=7 Participants	123 participants n=5 Participants
Race/Ethnicity, Customized Other	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 52, and FAP (up to Week 52)

Population: Full Analysis Set (FAS): all participants enrolled in the Treatment Phase, excluding those with objective measurements not meeting the major eligibility criteria, who did not receive ROP at all, and those with no valid post-baseline data. Last observation carried forward (LOCF) was used for the FAP data to impute post-baseline missing values.

The Japanese UPDRS assesses the status of Parkinson's Disease (PD) patients objectively. Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms. "On" state is where PD symptoms are well controlled by the drug. Participants with "off" state at baseline or without post-baseline data were not included in the ROP+L-dopa group at FAP. These participants as well as one with "off" state at Week 52 and those prematurely withdrawn were not included at Week 52.

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=65 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride n=58 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Mean Change From Baseline in the Japanese Unified Parkinson's Disease Rating Scale (UPDRS) Part III Total Score (in "On" State for the ROP+L-Dopa Group) at Week 52 and Final Assessment Point (FAP) Week 52, n=45, 46	-7.0 units on a scale Standard Deviation 8.17	-6.9 units on a scale Standard Deviation 7.56
Mean Change From Baseline in the Japanese Unified Parkinson's Disease Rating Scale (UPDRS) Part III Total Score (in "On" State for the ROP+L-Dopa Group) at Week 52 and Final Assessment Point (FAP) FAP, n=61, 58	-5.8 units on a scale Standard Deviation 8.33	-5.5 units on a scale Standard Deviation 8.08

SECONDARY outcome

Timeframe: Baseline, Week 52, and FAP (up to Week 52)

Population: FAS. LOCF was used for the FAP data to impute post-baseline missing values. One participant was not included in the ROP+L-dopa group at FAP as having no post-baseline data. This participant as well as those prematurely withdrawn from the study in each group was not included at Week 52.

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

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=65 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride n=58 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Mean Change From Baseline in the Japanese UPDRS Part I Total Score at Week 52 and FAP Week 52, n=47, 46	-0.4 units on a scale Standard Deviation 1.11	-0.1 units on a scale Standard Deviation 0.90
Mean Change From Baseline in the Japanese UPDRS Part I Total Score at Week 52 and FAP FAP, n=64, 58	-0.2 units on a scale Standard Deviation 1.26	-0.0 units on a scale Standard Deviation 0.96

SECONDARY outcome

Timeframe: Baseline, Week 52, and FAP (up to Week 52)

Population: FAS. LOCF was used for the FAP data to impute post-baseline missing values. Some participants were not included at FAP as having no post-baseline data in "on" state, not having "off" state at baseline, or no data in "off" state at Week 52/withdrawal. These participants as well as those prematurely withdrawn were not included at Week 52.

The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "On" state is where PD symptoms are well controlled by the drug. "Off" state is where PD symptoms are not adequately controlled by the drug.

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=65 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride n=32 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Mean Change From Baseline in the Japanese UPDRS Part II Total Score at Week 52 and FAP by "On"/"Off" State in the ROP+L-Dopa Group Week 52, n=47, 13	-3.5 units on a scale Standard Deviation 4.19	-2.8 units on a scale Standard Deviation 3.77
Mean Change From Baseline in the Japanese UPDRS Part II Total Score at Week 52 and FAP by "On"/"Off" State in the ROP+L-Dopa Group FAP, n=64, 22	-2.3 units on a scale Standard Deviation 4.54	-0.3 units on a scale Standard Deviation 6.46

SECONDARY outcome

Timeframe: Baseline, Week 52, and FAP (up to Week 52)

Population: FAS. LOCF was used for the FAP data to impute post-baseline missing values. Participants prematurely withdrawn from the study were not included at Week 52.

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

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=58 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Mean Change From Baseline in the Japanese UPDRS Part II Total Score at Week 52 and FAP in the ROP Group Week 52, n=46	-2.2 units on a scale Standard Deviation 3.60	—
Mean Change From Baseline in the Japanese UPDRS Part II Total Score at Week 52 and FAP in the ROP Group FAP, n=58	-1.8 units on a scale Standard Deviation 3.86	—

SECONDARY outcome

Timeframe: Baseline, Week 52, and FAP (up to Week 52)

Population: FAS. LOCF was used for the FAP data to impute post-baseline missing values. One participant was not included in the ROP+L-dopa group at FAP as having no post-baseline data. This participant as well as those prematurely withdrawn from the study in each group was not included at Week 52.

The Japanese UPDRS assesses the status of PD patients objectively. Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per item depending on the item. The maximum total score is 23 points. A higher score indicates more severe symptoms of complications.

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=65 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride n=58 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Mean Change From Baseline in the Japanese UPDRS Part IV Total Score at Week 52 and FAP Week 52, n=47, 46	0.1 units on a scale Standard Deviation 1.54	0.3 units on a scale Standard Deviation 1.24
Mean Change From Baseline in the Japanese UPDRS Part IV Total Score at Week 52 and FAP FAP, n=64, 58	0.3 units on a scale Standard Deviation 1.75	0.3 units on a scale Standard Deviation 1.15

SECONDARY outcome

Timeframe: Baseline, Week 52, and FAP (up to Week 52)

Population: FAS. LOCF was used for the FAP data to impute post-baseline missing values. One participant was not included in the ROP+L-dopa group at FAP as having no post-baseline data. This participant as well as those prematurely withdrawn from the study in each group was not included at Week 52.

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

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=65 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride n=58 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Japanese UPDRS Part I Mean Total Score at Baseline, Week 52, and FAP Baseline, n=65, 58	0.8 units on a scale Standard Deviation 1.35	0.8 units on a scale Standard Deviation 1.10
Japanese UPDRS Part I Mean Total Score at Baseline, Week 52, and FAP Week 52, n=47, 46	0.4 units on a scale Standard Deviation 0.77	0.7 units on a scale Standard Deviation 1.11
Japanese UPDRS Part I Mean Total Score at Baseline, Week 52, and FAP FAP, n=64, 58	0.7 units on a scale Standard Deviation 1.30	0.8 units on a scale Standard Deviation 1.15

SECONDARY outcome

Timeframe: Baseline, Week 52, and FAP (up to Week 52)

Population: FAS. LOCF was used for the FAP data to impute post-baseline missing values. Some participants were not included at FAP as having a baseline value of zero, which could not be used for calculating the percent change, or having no post-baseline data. These participants as well as those prematurely withdrawn in each group were not included at Week 52.

The Japanese UPDRS assesses the status of PD patients objectively. Part I assesses mentation, behavior, and mood on 4 items. Participants receive a score of 0-4 points per item. The maximum total score is 16 points. A higher score indicates more severe mental symptoms. Percent change from baseline was calculated as (change from baseline score/baseline score) \* 100; change from baseline was calculated as thescore at the observation day minus the baseline score.

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=65 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride n=58 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Mean Percent Change From Baseline in the Japanese UPDRS Part I Total Score at Week 52 and FAP Week 52, n=19, 22	-68.86 percent change in score Standard Deviation 41.929	-22.73 percent change in score Standard Deviation 79.772
Mean Percent Change From Baseline in the Japanese UPDRS Part I Total Score at Week 52 and FAP FAP, n=27, 26	-38.09 percent change in score Standard Deviation 109.715	-21.92 percent change in score Standard Deviation 73.595

SECONDARY outcome

Timeframe: Baseline, Week 52, and FAP (up to Week 52)

Population: FAS. Participants without "off" state at baseline were not included in the analysis of baseline "off" state data. Participants not included at FAP as well as those prematurely withdrawn from the study were not included at Week 52.

The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "On" state is where PD symptoms are well controlled by the drug. "Off" state is where PD symptoms are not adequately controlled by the drug. LOCF was used for the FAP data. Some participants were not included at FAP as having no post-baseline data in "on" state or having no data in "off" state at Week 52/withdrawal.

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=65 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride n=32 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Japanese UPDRS Part II Mean Total Score at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group Baseline, n=65, 27	7.9 units on a scale Standard Deviation 5.51	14.3 units on a scale Standard Deviation 9.04
Japanese UPDRS Part II Mean Total Score at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group Week 52, n=47, 16	4.1 units on a scale Standard Deviation 4.37	11.4 units on a scale Standard Deviation 5.93
Japanese UPDRS Part II Mean Total Score at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group FAP, n=64, 26	5.5 units on a scale Standard Deviation 6.18	15.2 units on a scale Standard Deviation 10.98

SECONDARY outcome

Timeframe: Baseline, Week 52, and FAP (up to Week 52)

Population: FAS. LOCF was used for the FAP data to impute post-baseline missing values. Participants prematurely withdrawn from the study were not included at Week 52.

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

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=58 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Japanese UPDRS Part II Mean Total Score at Baseline, Week 52, and FAP in ROP Group Baseline, n=58	7.7 units on a scale Standard Deviation 4.59	—
Japanese UPDRS Part II Mean Total Score at Baseline, Week 52, and FAP in ROP Group Week 52, n=46	5.4 units on a scale Standard Deviation 4.65	—
Japanese UPDRS Part II Mean Total Score at Baseline, Week 52, and FAP in ROP Group FAP, n=58	5.9 units on a scale Standard Deviation 4.52	—

SECONDARY outcome

Timeframe: Baseline, Week 52, and FAP (up to Week 52)

Population: FAS. LOCF was used for FAP data. Some participants were not included at FAP as having a baseline value of zero, having no post-baseline data in "on" state, not having "off" state at baseline in "off" state, or having no data at Week 52/withdrawal in "off" state. These participants as well as those prematurely withdrawn were not included at Week 52.

The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "On" state is where PD symptoms are well controlled by the drug. "Off" state is where PD symptoms are not adequately controlled by the drug. Percent change from baseline was calculated as (change from baseline score/baseline score) \* 100; change from baseline was calculated as thescore at the observation day minus the baseline score.

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=65 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride n=32 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Mean Percent Change From Baseline in the Japanese UPDRS Part II Total Score at Week 52 and FAP by "On"/"Off" State in the ROP+L-Dopa Group Week 52, n=47, 13	-48.98 percent change in score Standard Deviation 45.862	-17.68 percent change in score Standard Deviation 31.381
Mean Percent Change From Baseline in the Japanese UPDRS Part II Total Score at Week 52 and FAP by "On"/"Off" State in the ROP+L-Dopa Group FAP, n=62, 22	-29.00 percent change in score Standard Deviation 73.391	-4.10 percent change in score Standard Deviation 36.155

SECONDARY outcome

Timeframe: Baseline, Week 52, and FAP (up to Week 52)

Population: FAS. LOCF was used for the FAP data to impute post-baseline missing values. Some participants were not included at FAP as having a baseline value of zero, which could not be used for calculating the percent change. These participants as well as those prematurely withdrawn were not included at Week 52

The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. Percent change from baseline was calculated as (change from baseline score/baseline score) \* 100; change from baseline was calculated as thescore at the observation day minus the baseline score.

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=58 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Mean Percent Change From Baseline in the Japanese UPDRS Part II Total Score at Week 52 and FAP in the ROP Group Week 52, n=44	-24.35 percent change in score Standard Deviation 59.429	—
Mean Percent Change From Baseline in the Japanese UPDRS Part II Total Score at Week 52 and FAP in the ROP Group FAP, n=56	-16.74 percent change in score Standard Deviation 61.175	—

SECONDARY outcome

Timeframe: Baseline, Week 52, and FAP (up to Week 52)

Population: FAS. Participants having "off" state at baseline were not included in the ROP+L-dopa group at baseline. The participant not included in the FAP as well as one having "off" state in the ROP+L-dopa group at Week 52 and those prematurely withdrawn in each group were not included at Week 52.

The Japanese UPDRS assesses the status of PD patients objectively. Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms. "On" state is where PD symptoms are well controlled by the drug. LOCF was used for the FAP data to impute post-baseline missing values. One participant was not included in the ROP+L-dopa group at FAP as having no post-baseline data.

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=65 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride n=58 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Japanese UPDRS Part III Mean Total Score (in "On" State for the ROP+L-Dopa Group) at Baseline, Week 52, and FAP FAP, n=64, 58	14.3 units on a scale Standard Deviation 12.20	14.3 units on a scale Standard Deviation 11.01
Japanese UPDRS Part III Mean Total Score (in "On" State for the ROP+L-Dopa Group) at Baseline, Week 52, and FAP Baseline, n=62,58	20.5 units on a scale Standard Deviation 12.44	19.8 units on a scale Standard Deviation 12.10
Japanese UPDRS Part III Mean Total Score (in "On" State for the ROP+L-Dopa Group) at Baseline, Week 52, and FAP Week 52, n=46, 46	12.7 units on a scale Standard Deviation 10.26	13.1 units on a scale Standard Deviation 10.86

SECONDARY outcome

Timeframe: Baseline, Week 52, and FAP (up to Week 52)

Population: FAS. LOCF was used for the FAP data to impute post-baseline missing values. Participants with "off" state at baseline or without post-baseline data were not included in the ROP+L-dopa group at FAP. These participants as well as one with "off" state at Week 52 in that group and those prematurely withdrawn in each group were not included at Week 52.

The Japanese UPDRS assesses the status of PD patients objectively. Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms. "On" state is where PD symptoms are well controlled by the drug. Percent change from baseline was calculated as (change from baseline score/baseline score) \* 100; change from baseline was calculated as thescore at the observation day minus the baseline score.

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=65 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride n=58 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Mean Percent Change From Baseline in the Japanese UPDRS Part III Total Score (in "On" State for the ROP+L-Dopa Group) at Week 52 and FAP Week 52, n=45, 46	-36.83 percent change in score Standard Deviation 40.001	-37.73 percent change in score Standard Deviation 34.739
Mean Percent Change From Baseline in the Japanese UPDRS Part III Total Score (in "On" State for the ROP+L-Dopa Group) at Week 52 and FAP FAP, n=61, 58	-30.42 percent change in score Standard Deviation 41.427	-27.79 percent change in score Standard Deviation 42.531

SECONDARY outcome

Timeframe: Baseline, Week 52, and FAP (up to Week 52)

Population: FAS. LOCF was used for the FAP data to impute post-baseline missing values. One participant was not included in the ROP+L-dopa group at FAP as having no post-baseline data. This participant as well as those prematurely withdrawn from the study in each group was not included at Week 52.

The Japanese UPDRS assesses the status of PD patients objectively. Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per item depending on the item. The maximum total score is 23 points. A higher score indicates more severe symptoms of complications.

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=65 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride n=58 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Japanese UPDRS Part IV Mean Total Score at Baseline, Week 52, and FAP Baseline, n=65, 58	2.1 units on a scale Standard Deviation 3.01	0.5 units on a scale Standard Deviation 1.17
Japanese UPDRS Part IV Mean Total Score at Baseline, Week 52, and FAP Week 52, n=47, 46	1.5 units on a scale Standard Deviation 1.77	0.8 units on a scale Standard Deviation 1.33
Japanese UPDRS Part IV Mean Total Score at Baseline, Week 52, and FAP FAP, n=64, 58	2.4 units on a scale Standard Deviation 3.30	0.8 units on a scale Standard Deviation 1.26

SECONDARY outcome

Timeframe: Baseline, Week 52, and FAP (up to Week 52)

Population: FAS. LOCF was used for the FAP data to impute post-baseline missing values. Some participants were not included at FAP as having a baseline value of zero, which could not be used for calculating the percent change, or having no post-baseline data. These participants as well as those prematurely withdrawn from the study were not included at Week 52.

The Japanese UPDRS assesses the status of PD patients objectively. Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per 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 was calculated as (change from baseline score/baseline score) \* 100; change from baseline was calculated as thescore at the observation day minus the baseline score.

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=65 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride n=58 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Mean Percent Change From Baseline in the Japanese UPDRS Part IV Total Score at Week 52 and FAP Week 52, n=23, 17	-8.70 percent change in score Standard Deviation 62.889	0.00 percent change in score Standard Deviation 115.920
Mean Percent Change From Baseline in the Japanese UPDRS Part IV Total Score at Week 52 and FAP FAP, n=37, 20	13.30 percent change in score Standard Deviation 91.068	-2.50 percent change in score Standard Deviation 109.394

SECONDARY outcome

Timeframe: Baseline, Week 52, and FAP (up to Week 52)

Population: FAS. Participants without "off" state at baseline were not included in the analysis of baseline "off" state data. Participants not included at FAP as well as those prematurely withdrawn from the study were not included at Week 52.

The Modified Hoehn \& Yahr criteria are measured on the following 8-point scale for staging: 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; 4, Severe disability; and 5, Wheelchair bound or bedridden unless aided. LOCF was used for the FAP data to impute post-baseline missing values. Some participants in each state were not included at FAP as having no post-baseline data in the corresponding state or having no data in the corresponding state at Week 52/withdrawal.

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=65 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride n=32 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group Baseline, n=65, 27, Stage 1.5	3 participants	1 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group Week 52, n=47, 16, Stage 3	8 participants	4 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group Week 52, n=47, 16, Stage 5	0 participants	1 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group FAP, n=63, 25, Stage 0	1 participants	0 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group FAP, n=63, 25, Stage 1	13 participants	1 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group FAP, n=63, 25, Stage 1.5	7 participants	1 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group FAP, n=63, 25, Stage 2	21 participants	1 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group FAP, n=63, 25, Stage 2.5	7 participants	5 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group FAP, n=63, 25, Stage 3	11 participants	7 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group FAP, n=63, 25, Stage 4	3 participants	7 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group FAP, n=63, 25, Stage 5	0 participants	3 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group Baseline, n=65, 27, Stage 0	0 participants	0 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group Baseline, n=65, 27, Stage 1	5 participants	0 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group Baseline, n=65, 27, Stage 2	22 participants	2 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group Baseline, n=65, 27, Stage 2.5	16 participants	9 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group Baseline, n=65, 27, Stage 3	16 participants	7 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group Baseline, n=65, 27, Stage 4	3 participants	6 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group Baseline, n=65, 27, Stage 5	0 participants	2 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group Week 52, n=47, 16, Stage 0	1 participants	0 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group Week 52, n=47, 16, Stage 1	10 participants	1 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group Week 52, n=47, 16, Stage 1.5	6 participants	1 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group Week 52, n=47, 16, Stage 2	15 participants	1 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group Week 52, n=47, 16, Stage 2.5	6 participants	4 participants
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group Week 52, n=47, 16, Stage 4	1 participants	4 participants

SECONDARY outcome

Timeframe: Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group

Population: FAS. LOCF was used for the FAP data to impute post-baseline missing values. Participants prematurely withdrawn from the study were not included at Week 52.

The Modified Hoehn \& Yahr criteria are measured on the following 8-point scale for staging: 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; 4, Severe disability; and 5, Wheelchair bound or bedridden unless aided.

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=58 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group FAP, n=58, Stage 2	17 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group FAP, n=58, Stage 2.5	18 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group Baseline, n=58, Stage 0	0 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group Baseline, n=58, Stage 1	9 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group Baseline, n=58, Stage 1.5	2 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group Baseline, n=58, Stage 2	21 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group Baseline, n=58, Stage 2.5	14 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group Baseline, n=58, Stage 3	12 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group Baseline, n=58, Stage 4	0 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group Baseline, n=58, Stage 5	0 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group Week 52, n=46, Stage 0	1 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group Week 52, n=46, Stage 1	12 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group Week 52, n=46, Stage 1.5	1 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group Week 52, n=46, Stage 2	14 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group Week 52, n=46, Stage 2.5	13 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group Week 52, n=46, Stage 3	5 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group Week 52, n=46, Stage 4	0 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group Week 52, n=46, Stage 5	0 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group FAP, n=58, Stage 0	1 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group FAP, n=58, Stage 1	13 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group FAP, n=58, Stage 1.5	2 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group FAP, n=58, Stage 3	7 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group FAP, n=58, Stage 4	0 participants	—
Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group FAP, n=58, Stage 5	0 participants	—

SECONDARY outcome

Timeframe: Baseline, Week 52, and FAP (up to Week 52)

Population: FAS. LOCF was used for the FAP data. Some participants were not included at FAP as having no post-baseline data in "on" state, not having "off" state at baseline in "off" state, or having no data in the corresponding state at Week 52/withdrawal. These participants as well as those prematurely withdrawn were not included at Week 52.

The Schwab and England Activities of Daily Living Scale Score is measured as percentage, from 100% (Completely independent. Able to do all chores without slowness, difficulty or impairment. Essentially normal. Unaware of any difficulty) to 0% (Vegetative functions such as swallowing, bladder and bowel functions are not functioning. Bedridden).

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=65 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride n=32 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Mean Change From Baseline in the Schwab and England Activities of Daily Living Scale Score by Clinician at Week 52 and FAP by "On"/"Off" State in the ROP+L-Dopa Group Week 52, n=47, 13	3.4 percent change Standard Deviation 10.52	5.8 percent change Standard Deviation 16.31
Mean Change From Baseline in the Schwab and England Activities of Daily Living Scale Score by Clinician at Week 52 and FAP by "On"/"Off" State in the ROP+L-Dopa Group FAP, n=63, 21	3.0 percent change Standard Deviation 9.97	2.6 percent change Standard Deviation 14.63

SECONDARY outcome

Timeframe: Baseline, Week 52, and FAP (up to Week 52)

Population: FAS. LOCF was used for the FAP data to impute post-baseline missing values. Participants prematurely withdrawn from the study were not included at Week 52.

The Schwab and England Activities of Daily Living Scale Score is measured as percentage, from 100% (Completely independent. Able to do all chores without slowness, difficulty or impairment. Essentially normal. Unaware of any difficulty) to 0% (Vegetative functions such as swallowing, bladder and bowel functions are not functioning. Bedridden).

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=58 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Mean Change From Baseline in the Schwab and England Activities of Daily Living Scale Score by Clinician at Week 52 and FAP in ROP Group Week 52, n=46	2.1 percent change Standard Deviation 6.74	—
Mean Change From Baseline in the Schwab and England Activities of Daily Living Scale Score by Clinician at Week 52 and FAP in ROP Group FAP, n=58	1.5 percent change Standard Deviation 7.28	—

SECONDARY outcome

Timeframe: Days 0-422

Population: FAS

The percentage of participants remaining in the study was presented by Kaplan-Meier method, where premature discontinuation (i.e., withdrawal before Week 52) was the event, and participants who had completed the study were censored.

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=65 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group Day 43	94 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group Day 85	92 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group Day 101	91 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group Day 112	89 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group Day 128	88 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group Day 154	86 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group Day 169	83 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group Day 196	82 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group Day 203	80 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group Day 238	78 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group Day 282	77 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group Day 301	75 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group Day 341	74 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group Day 365	72 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group Day 422	72 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group Day 0	100 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group Day 22	98 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group Day 33	95 percentage of participants	—

SECONDARY outcome

Timeframe: Days 0-419

Population: FAS

The percentage of participants remaining in the study was presented by Kaplan-Meier method, where premature discontinuation (i.e., withdrawal before Week 52) was the event, and participants who had completed the study were censored.

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=58 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP Group Day 0	100 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP Group Day 14	98 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP Group Day 29	97 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP Group Day 36	95 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP Group Day 66	93 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP Group Day 71	91 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP Group Day 85	90 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP Group Day 167	88 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP Group Day 169	86 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP Group Day 175	84 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP Group Day 210	83 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP Group Day 241	81 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP Group Day 253	79 percentage of participants	—
Percentage of Participants Remaining in the Study on the Indicated Days in the ROP Group Day 419	79 percentage of participants	—

SECONDARY outcome

Timeframe: Week 52 and FAP (up to Week 52)

Population: FAS. LOCF was used for the FAP data to impute post-baseline missing values. One participant was not included in the ROP+L-dopa group at FAP as having no post-baseline data. This participant as well as those prematurely withdrawn from the study in each group was not included at Week 52.

CGI is measured on the following 7-point scale: 1, Very much improved; 2, Much Improved; 3, Minimally improved; 4, No change; 5, Minimally worse; 6, Much worse; and 7, Very much worse. Responders are defined as those participants scored as "very much improved" or "much improved."

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=65 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride n=58 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Number of Participants Scored as Responders on the Clinician's Global Impression (CGI) Scale at Week 52 and FAP Week 52, n=47, 46	33 participants	28 participants
Number of Participants Scored as Responders on the Clinician's Global Impression (CGI) Scale at Week 52 and FAP FAP, n=64, 58	34 participants	31 participants

SECONDARY outcome

Timeframe: Baseline, Week 52, and FAP (up to Week 52)

Population: FAS. LOCF was used for the FAP data to impute post-baseline missing values. Participants having "off" hour of zero at baseline were not included at FAP. These participants as well as those prematurely withdrawn from the study were not included at Week 52.

"Off" state is where PD symptoms are not adequately controlled by the drug. "On" state is where PD symptoms are well controlled by the drug. The "off's" duration (awake time spent "off") and the "on's" duration (awake time spent "on") on each day were calculated.

Outcome measures

Outcome measures
Measure	ROP+L-Dopa n=65 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride n=65 Participants Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Mean Change From Baseline in Awake Time "Off" (Hours) and Awake Time "On" (Hours) at Week 52 and FAP in the ROP+L-Dopa Group Excluding Participants With "0" Off (Hour) at Baseline Week 52, n=16	-0.09 hours Standard Deviation 3.502	1.00 hours Standard Deviation 4.090
Mean Change From Baseline in Awake Time "Off" (Hours) and Awake Time "On" (Hours) at Week 52 and FAP in the ROP+L-Dopa Group Excluding Participants With "0" Off (Hour) at Baseline FAP, n=22	-0.40 hours Standard Deviation 3.453	1.00 hours Standard Deviation 3.867

Adverse Events

ROP+L-Dopa

Serious events: 7 serious events

Other events: 42 other events

Deaths: 0 deaths

Ropinirole Hydrochloride

Serious events: 3 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ROP+L-Dopa n=65 participants at risk Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride n=58 participants at risk Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Injury, poisoning and procedural complications Meniscus lesion	1.5% 1/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	0.00% 0/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Injury, poisoning and procedural complications Spinal compression fracture	1.5% 1/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	0.00% 0/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Nervous system disorders Parkinson's Disease	1.5% 1/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	0.00% 0/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Nervous system disorders Sudden onset of sleep	1.5% 1/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	0.00% 0/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Ear and labyrinth disorders Vertigo	1.5% 1/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	0.00% 0/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Eye disorders Cataract	0.00% 0/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	1.7% 1/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Infections and infestations Pyelonephritis	1.5% 1/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	0.00% 0/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Metabolism and nutrition disorders Dehydration	0.00% 0/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	1.7% 1/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Musculoskeletal and connective tissue disorders Back pain	1.5% 1/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	0.00% 0/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer recurrent	0.00% 0/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	1.7% 1/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	ROP+L-Dopa n=65 participants at risk Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study.	Ropinirole Hydrochloride n=58 participants at risk Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study.
Nervous system disorders Somnolence	24.6% 16/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	24.1% 14/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Nervous system disorders Headache	6.2% 4/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	5.2% 3/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Nervous system disorders Parkinson's Disease	10.8% 7/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	0.00% 0/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Nervous system disorders Sudden onset of sleep	4.6% 3/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	5.2% 3/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Nervous system disorders Dizziness	0.00% 0/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	6.9% 4/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Nervous system disorders Dyskinesia	6.2% 4/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	0.00% 0/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Nervous system disorders Tremor	0.00% 0/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	5.2% 3/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Infections and infestations Nasopharyngitis	20.0% 13/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	32.8% 19/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Gastrointestinal disorders Nausea	10.8% 7/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	6.9% 4/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Gastrointestinal disorders Constipation	10.8% 7/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	3.4% 2/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Gastrointestinal disorders Dental caries	3.1% 2/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	5.2% 3/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Gastrointestinal disorders Stomatitis	1.5% 1/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	5.2% 3/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Gastrointestinal disorders Gastritis	0.00% 0/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	5.2% 3/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Musculoskeletal and connective tissue disorders Back pain	6.2% 4/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	6.9% 4/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Musculoskeletal and connective tissue disorders Arthralgia	1.5% 1/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	5.2% 3/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Psychiatric disorders Hallucination	6.2% 4/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	8.6% 5/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Vascular disorders Orthostatic hypotension	4.6% 3/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	8.6% 5/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Injury, poisoning and procedural complications Contusion	6.2% 4/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	5.2% 3/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).
Metabolism and nutrition disorders Decreased appetite	1.5% 1/65 • From Baseline (Week 0) through the end of follow-up (up to Week 56).	5.2% 3/58 • From Baseline (Week 0) through the end of follow-up (up to Week 56).