Long-term Extension Study Evaluating Extended Release Ropinirole XL (Formerly Referred to as Ropinirole CR) in Patients Who Already Completed Either Study 167 or 164

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00650104
• Collaborator: (none)
• Enrollment: 76
• Locations: 10
• Arm: 1
• Duration (Months): 82
• Patients Per Site: 7.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to obtain information on the long-term safety, tolerability, and therapeutic benefit of extended release ropinirole XL, and to provide a mechanism for patients who participated in either Study 167 or Study 164 to continue receiving ropinirole XL if they chose to do so.

Condition or Disease	Intervention/Treatment	Phase
Parkinson Disease	Drug: Ropinirole XL (formerly CR)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 76 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 101648/196: A Long-Term, Open-Label Continuation Study of Once Daily Administration of Ropinirole CR Tablets to Patients With Parkinson's Disease Who Completed the Previous Ropinirole CR Studies 167 or 164
• Study Start Date: May 1, 2002
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Active Open label medication - Ropinirole CR	Drug: Ropinirole XL (formerly CR); Active Ropinirole CR tablets of 2.0mg, 4.0mg, 8.0mg where subjects can tritrate to an stable optimum dose level of either 2.0mg, 4.0mg, 6.0mg, 8.0mg, 12mg, 16mg, 20mg, or 24mg per day.

Outcome Measures

Primary Outcome Measures

1. Unified Parkinson's Disease (PD) Rating Scale (UPDRS) Total Activities of Daily Living Scores (Intent-to-Treat Population) [Screening; Week 4; Months 3, 9, 15, 21, 27, 33, 39, 45, 51, 57, 63, 69, 75, and 78]

   The UPDRS is a clinician-based scale used to assess the longitudinal course of PD. Two of the six sections were assessed (Part II, Activities of Daily Living (ADL); Part III, Motor Examination). Both consist of a number of items (ADL, 13 items; Motor Exam., 17 items), and each item has a choice of 5 responses that are numerically scored 0-4, with 0 as the least severe response and 4 as the most severe response. ADL final score is a sum of the 13 items and may have a value between 0 (no impairment of overall activities) and 52 (severe impairment of overall activities). LTT, long-term treatment.

2. Number of Participants With the Indicated Number of Adverse Events (AEs) [Every study visit from baseline to market availability (Month 78)]

   AEs, defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, were collected to obtain data on the safety, tolerability, and benefit of ropinirole XL. Serious Adverse Events (SAEs), defined as AEs that are either fatal, life threatening, disabling/incapacitating, resulting in hospitalization or prolongation of a hospital stay, a congenital abnormality/birth defect, or any important medical occurrence that the investigator regards as serious based on medical judgment, were also collected. st. med., study medication.

Secondary Outcome Measures

1. Unified Parkinson's Disease Rating Scale (UPDRS) Total Activities of Daily Living Score (Responder Population) [Screening; Months 3, 9, 15, 27, and 78]

   The UPDRS is a clinician-based scale used to assess the longitudinal course of PD. Two of the six sections were assessed (Part II, Activities of Daily Living (ADL); Part III, Motor Examination). Both consist of a number of items (ADL, 13 items; Motor Exam., 17 items), and each item has a choice of 5 responses that are numerically scored 0-4, with 0 as the least severe response and 4 as the most severe response. ADL final score is a sum of the 13 items and may have a value between 0 (no impairment of overall activities) and 52 (severe impairment of overall activities). LTT, long-term treatment.

2. Unified Parkinson's Disease Rating Scale (UPDRS) Total Activities of Daily Living Scores (Maintained Responder Population) [Screening; Months 3, 9, 15, 27, and 78]

   The UPDRS is a clinician-based scale used to assess the longitudinal course of PD. Two of the six sections were assessed (Part II, Activities of Daily Living (ADL); Part III, Motor Examination). Both consist of a number of items (ADL, 13 items; Motor Exam., 17 items), and each item has a choice of 5 responses that are numerically scored 0-4, with 0 as the least severe response and 4 as the most severe response. ADL final score is a sum of the 13 items and may have a value between 0 (no impairment of overall activities) and 52 (severe impairment of overall activities). LTT, long-term treatment.

3. Unified Parkinson's Disease Rating Scale (UPDRS) Motor Examination Score (ITT Population) [Screening and Month 78]

   Two of the six UPDRS sections (Part II, Activities of Daily Living (ADL); Part III, Motor Examination) were assessed in this study. The Motor Exam has 17 items, some of which are assessed in both the left and right extremities. Each item has a choice of 5 responses that are numerically scored 0-4 (0 as the least severe, 4 as the most severe). The final score is a sum of the 17 items, with some sections requiring multiple grades assigned to each extremity, and has a value ranging from 0 (no motor impairment) to 108 (severe motor impairment).

4. Unified Parkinson's Disease Rating Scale (UPDRS) Motor Examination Score (Reponder Population) [Screening and Month 78]

   Two of the six UPDRS sections (Part II, Activities of Daily Living (ADL); Part III, Motor Examination) were assessed in this study. The Motor Exam has 17 items, some of which are assessed in both the left and right extremities. Each item has a choice of 5 responses that are numerically scored 0-4 (0 as the least severe, 4 as the most severe). The final score is a sum of the 17 items, with some sections requiring multiple grades assigned to each extremity, and has a value ranging from 0 (no motor impairment) to 108 (severe motor impairment).

5. Unified Parkinson's Disease Rating Scale (UPDRS) Motor Examination Score (Maintained Responder Population) [Screening and Month 78]

   Two of the six UPDRS sections (Part II, Activities of Daily Living (ADL); Part III, Motor Examination) were assessed in this study. The Motor Exam has 17 items, some of which are assessed in both the left and right extremities. Each item has a choice of 5 responses that are numerically scored 0-4 (0 as the least severe, 4 as the most severe). The final score is a sum of the 17 items, with some sections requiring multiple grades assigned to each extremity, and has a value ranging from 0 (no motor impairment) to 108 (severe motor impairment).

6. Number of Participants With the Indicated Responses for CGI Global Impression (CGI-I) (ITT Population) [Week 2, Month 12, Month 78]

   The Clinical Global Impression (CGI) scale comprises the following three components (CGI-Severity, CGI-Improvement, Index); where only the CGI-S and CGI-I were assessed in this study. CGI-I is a global improvement scale that scores the clinician's view of the participant's global functioning prior to and after initiating a study medication from 1 (very much improved) to 7 (very much worse). 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse.

7. Number of Participants With the Indicated Responses for CGI Global Impression (CGI-I) (Responder Population) [Week 2, Month 12, Month 78]

   The Clinical Global Impression (CGI) scale comprises the following three components (CGI-Severity, CGI-Improvement, Index); where only the CGI-S and CGI-I were assessed in this study. CGI-I is a global improvement scale that scores the clinician's view of the participant's global functioning prior to and after initiating a study medication from 1 (very much improved) to 7 (very much worse). 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse.

8. Number of Participants With the Indicated Responses for CGI Global Impression (CGI-I) (Maintained Responder Population) [Week 2, Month 12, Month 78]

   The Clinical Global Impression (CGI) scale comprises the following three components (CGI-Severity, CGI-Improvement, Index); where only the CGI-S and CGI-I were assessed in this study. CGI-I is a global improvement scale that scores the clinician's view of the participant's global functioning prior to and after initiating a study medication from 1 (very much improved) to 7 (very much worse). 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 30 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males or non-pregnant/non-breast feeding females

• At least 30 years of age

• Diagnosis of idiopathic Parkinson''s disease (Hoehn & Yahr criteria)

• Completed either Study 167 or Study 164

Exclusion Criteria:

• Presence of uncontrolled psychiatric, hematological, renal, hepatic,endocrinological, neurological, cardiovascular disease or active malignancy

• Dizziness or fainting due to orthostatic hypotension on standing

• Significant sleep disorder

• Drug abuse or alcoholism

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Scottsdale	Arizona	United States	85259
2	GSK Investigational Site	Los Angeles	California	United States	90033
3	GSK Investigational Site	Oxnard	California	United States	93030
4	GSK Investigational Site	Miami	Florida	United States	33136
5	GSK Investigational Site	Tampa	Florida	United States	33606
6	GSK Investigational Site	Augusta	Georgia	United States	30912
7	GSK Investigational Site	Kansas City	Kansas	United States	66160
8	GSK Investigational Site	Edison	New Jersey	United States	08818
9	GSK Investigational Site	Upland	Pennsylvania	United States	19013
10	GSK Investigational Site	Houston	Texas	United States	77030

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

• Hauser RA, Reichmann H, Lew M, Asgharian A, Makumi C, Shulman KJ. Long-term, open-label study of once-daily ropinirole prolonged release in early Parkinson's disease. Int J Neurosci. 2011 May;121(5):246-53. doi: 10.3109/00207454.2010.546538. Epub 2011 Jan 19.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00650104
• Other Study ID Numbers: 101468/196
• First Posted: Apr 1, 2008
• Last Update Posted: May 6, 2013
• Last Verified: Apr 1, 2013

• Keywords provided by GlaxoSmithKline: ropinirole IR; efficacy; safety; open-label; long term safety; REQUIP; ropinirole XL; ropinirole CR; Parkinson's disease
• Additional relevant MeSH terms: Parkinson Disease; Ropinirole

Study Results

Participant Flow

Pre-assignment Detail	Study 101468/196 (this study; NCT#00650104) was an open-label, ropinirole XL (2-24 mg/day), continuation study for participants with Parkinson's Disease who previously completed Studies 167 or 164. Treatment was originally designed to continue for 3 years, but it was extended until ropinirole XL became commercially available in each study country.

Arm/Group Title	Ropinirole XL
Arm/Group Description	Up-titration: some participants from Study 167 started at 2 milligrams (mg) ropinirole XL once daily. Then, depending on the response/tolerance of each participant, the dose was increased in 1 mg weekly increments to 4 mg, then 2 mg weekly increments up to 12 mg, and in either 2 mg or 4 mg weekly increments up to 24 mg to the clinical optimum dose. Other Study 167 participants were increased in 2 mg weekly increments up to 8 mg and then 4 mg weekly increments up to 24 mg. Study 164 particiapnts who were on an optimal dose of ropinirole XL could go straight into the long-term treatment period, and those who were receiving ropinirole IR could be switched to the corresponding XL dose. Long-term treatment: participants received study medication until market availability of ropinirole XL. After market availability, participants would undergo a 1-week down-titration period; after protocol amendment #4 approval, participants could switch directly to the market-available dose.
Period Title: Overall Study
STARTED	83
COMPLETED	42
NOT COMPLETED	41

Baseline Characteristics

Arm/Group Title	Ropinirole XL
Arm/Group Description	Up-titration: some participants from Study 167 started at 2 milligrams (mg) ropinirole XL once daily. Then, depending on the response/tolerance of each participant, the dose was increased in 1 mg weekly increments to 4 mg, then 2 mg weekly increments up to 12 mg, and in either 2 mg or 4 mg weekly increments up to 24 mg to the clinical optimum dose. Other Study 167 participants were increased in 2 mg weekly increments up to 8 mg and then 4 mg weekly increments up to 24 mg. Study 164 particiapnts who were on an optimal dose of ropinirole XL could go straight into the long-term treatment period, and those who were receiving ropinirole IR could be switched to the corresponding XL dose. Long-term treatment: participants received study medication until market availability of ropinirole XL. After market availability, participants would undergo a 1-week down-titration period; after protocol amendment #4 approval, participants could switch directly to the market-available dose.
Overall Participants	83
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.1 (9.85)
Sex: Female, Male (Count of Participants)
Female	37 44.6%
Male	46 55.4%
Race/Ethnicity, Customized (participants) [Number]
Caucasian	74 89.2%
Hispanic	6 7.2%
Black	1 1.2%
Asian	1 1.2%
Other	1 1.2%
Weight (kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms (kg)]	79.24 (16.8)

Outcome Measures

1. Primary Outcome

Title	Unified Parkinson's Disease (PD) Rating Scale (UPDRS) Total Activities of Daily Living Scores (Intent-to-Treat Population)
Description	The UPDRS is a clinician-based scale used to assess the longitudinal course of PD. Two of the six sections were assessed (Part II, Activities of Daily Living (ADL); Part III, Motor Examination). Both consist of a number of items (ADL, 13 items; Motor Exam., 17 items), and each item has a choice of 5 responses that are numerically scored 0-4, with 0 as the least severe response and 4 as the most severe response. ADL final score is a sum of the 13 items and may have a value between 0 (no impairment of overall activities) and 52 (severe impairment of overall activities). LTT, long-term treatment.
Time Frame	Screening; Week 4; Months 3, 9, 15, 21, 27, 33, 39, 45, 51, 57, 63, 69, 75, and 78

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants who received at least one dose of study medication and who had at least one treatment period evaluation for any parameter were included in the evaluation of the therapeutic benefit. Various "n" values are the result of participant attrition.

Arm/Group Title	Ropinirole XL
Arm/Group Description	Up-titration: some participants from Study 167 started at 2 milligrams (mg) ropinirole XL once daily. Then, depending on the response/tolerance of each participant, the dose was increased in 1 mg weekly increments to 4 mg, then 2 mg weekly increments up to 12 mg, and in either 2 mg or 4 mg weekly increments up to 24 mg to the clinical optimum dose. Other Study 167 participants were increased in 2 mg weekly increments up to 8 mg and then 4 mg weekly increments up to 24 mg. Study 164 particiapnts who were on an optimal dose of ropinirole XL could go straight into the long-term treatment period, and those who were receiving ropinirole IR could be switched to the corresponding XL dose. Long-term treatment: participants received study medication until market availability of ropinirole XL. After market availability, participants would undergo a 1-week down-titration period; after protocol amendment #4 approval, participants could switch directly to the market-available dose.
Measure Participants	83
Screening, n=83	9.4 (5.14)
Up-titration (Week 4), n=64	8.9 (4.60)
LTT, Month 3, n=76	8.2 (5.34)
LTT, Month 9, n=72	8.1 (5.03)
LTT, Month 15, n=67	9.0 (5.83)
LTT, Month 21, n=63	8.6 (5.01)
LTT, Month 27, n=58	9.3 (5.59)
LTT, Month 33, n=53	10.3 (6.14)
LTT, Month 39, n=19	10.5 (6.74)
LTT, Month 45, n=18	9.3 (4.47)
LTT, Month 51, n=19	10.1 (6.07)
LTT, Month 57, n=20	10.4 (5.80)
LTT, Month 63, n=19	11.9 (7.23)
LTT, Month 69, n=20	10.8 (6.70)
LTT, Month 75, n=16	12.6 (6.66)
LTT, Month 78, n=13	11.5 (6.64)

2. Primary Outcome

Title	Number of Participants With the Indicated Number of Adverse Events (AEs)
Description	AEs, defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, were collected to obtain data on the safety, tolerability, and benefit of ropinirole XL. Serious Adverse Events (SAEs), defined as AEs that are either fatal, life threatening, disabling/incapacitating, resulting in hospitalization or prolongation of a hospital stay, a congenital abnormality/birth defect, or any important medical occurrence that the investigator regards as serious based on medical judgment, were also collected. st. med., study medication.
Time Frame	Every study visit from baseline to market availability (Month 78)

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study medication. The treatment-emergent Study 196 AEs were defined as occurring during "initial titration" or "long-term treatment" or "follow up".

Arm/Group Title	Ropinirole XL
Arm/Group Description	Up-titration: some participants from Study 167 started at 2 milligrams (mg) ropinirole XL once daily. Then, depending on the response/tolerance of each participant, the dose was increased in 1 mg weekly increments to 4 mg, then 2 mg weekly increments up to 12 mg, and in either 2 mg or 4 mg weekly increments up to 24 mg to the clinical optimum dose. Other Study 167 participants were increased in 2 mg weekly increments up to 8 mg and then 4 mg weekly increments up to 24 mg. Study 164 particiapnts who were on an optimal dose of ropinirole XL could go straight into the long-term treatment period, and those who were receiving ropinirole IR could be switched to the corresponding XL dose. Long-term treatment: participants received study medication until market availability of ropinirole XL. After market availability, participants would undergo a 1-week down-titration period; after protocol amendment #4 approval, participants could switch directly to the market-available dose.
Measure Participants	83
Participants (Par.) with at least one event	81 97.6%
Par. with 0 events	2 2.4%
Par. with 1 event	1 1.2%
Par. with 2 events	0 0%
Par. with ≥3 events	80 96.4%
Par. with mild AEs (by maximum intensity)	3 3.6%
Par. with moderate AEs (by maximum intensity)	38 45.8%
Par. with severe AEs (by maximum intensity)	40 48.2%
Par. with AEs not related to st. med.	6 7.2%
Par. with AEs not likely related to st. med.	6 7.2%
Par. with AEs suspected to be related to st. med.	36 43.4%
Par. with AEs probably related to st. med.	33 39.8%
Par. who withdrew study due to AEs	20 24.1%
Par. reporting SAEs	35 42.2%

3. Secondary Outcome

Title	Unified Parkinson's Disease Rating Scale (UPDRS) Total Activities of Daily Living Score (Responder Population)
Description	The UPDRS is a clinician-based scale used to assess the longitudinal course of PD. Two of the six sections were assessed (Part II, Activities of Daily Living (ADL); Part III, Motor Examination). Both consist of a number of items (ADL, 13 items; Motor Exam., 17 items), and each item has a choice of 5 responses that are numerically scored 0-4, with 0 as the least severe response and 4 as the most severe response. ADL final score is a sum of the 13 items and may have a value between 0 (no impairment of overall activities) and 52 (severe impairment of overall activities). LTT, long-term treatment.
Time Frame	Screening; Months 3, 9, 15, 27, and 78

Outcome Measure Data

Analysis Population Description

Responder: a subset of the ITT Population containing those participants who had a score of 1 (very much improved) or 2 (much improved) on the clinical global impression (CGI) scale during the study. CGI-I scores (1 to 7 [very much worse]) the participant's condition relative to baseline. Various "n" values are the result of participant attrition.

Arm/Group Title	Ropinirole XL
Arm/Group Description	Up-titration: some participants from Study 167 started at 2 milligrams (mg) ropinirole XL once daily. Then, depending on the response/tolerance of each participant, the dose was increased in 1 mg weekly increments to 4 mg, then 2 mg weekly increments up to 12 mg, and in either 2 mg or 4 mg weekly increments up to 24 mg to the clinical optimum dose. Other Study 167 participants were increased in 2 mg weekly increments up to 8 mg and then 4 mg weekly increments up to 24 mg. Study 164 particiapnts who were on an optimal dose of ropinirole XL could go straight into the long-term treatment period, and those who were receiving ropinirole IR could be switched to the corresponding XL dose. Long-term treatment: participants received study medication until market availability of ropinirole XL. After market availability, participants would undergo a 1-week down-titration period; after protocol amendment #4 approval, participants could switch directly to the market-available dose.
Measure Participants	60
Screening, n=60	9.1 (5.08)
LTT, Month 3, n=59	8.0 (5.18)
LTT, Month 9, n=58	7.8 (4.92)
LTT, Month 15, n=55	8.7 (5.76)
LTT, Month 27, n=47	8.8 (5.80)
LTT, Month 78, n=13	11.5 (6.64)

4. Secondary Outcome

Title	Unified Parkinson's Disease Rating Scale (UPDRS) Total Activities of Daily Living Scores (Maintained Responder Population)
Description	The UPDRS is a clinician-based scale used to assess the longitudinal course of PD. Two of the six sections were assessed (Part II, Activities of Daily Living (ADL); Part III, Motor Examination). Both consist of a number of items (ADL, 13 items; Motor Exam., 17 items), and each item has a choice of 5 responses that are numerically scored 0-4, with 0 as the least severe response and 4 as the most severe response. ADL final score is a sum of the 13 items and may have a value between 0 (no impairment of overall activities) and 52 (severe impairment of overall activities). LTT, long-term treatment.
Time Frame	Screening; Months 3, 9, 15, 27, and 78

Outcome Measure Data

Analysis Population Description

Maintained Responder : subset of the Responder Population, which was maintained or further decreased for a minimum of 4 weeks whilst the participant received a stable or decreasing dose of study medication. Various "n" values are the result of participant attrition.

Arm/Group Title	Ropinirole XL
Arm/Group Description	Up-titration: some participants from Study 167 started at 2 milligrams (mg) ropinirole XL once daily. Then, depending on the response/tolerance of each participant, the dose was increased in 1 mg weekly increments to 4 mg, then 2 mg weekly increments up to 12 mg, and in either 2 mg or 4 mg weekly increments up to 24 mg to the clinical optimum dose. Other Study 167 participants were increased in 2 mg weekly increments up to 8 mg and then 4 mg weekly increments up to 24 mg. Study 164 particiapnts who were on an optimal dose of ropinirole XL could go straight into the long-term treatment period, and those who were receiving ropinirole IR could be switched to the corresponding XL dose. Long-term treatment: participants received study medication until market availability of ropinirole XL. After market availability, participants would undergo a 1-week down-titration period; after protocol amendment #4 approval, participants could switch directly to the market-available dose.
Measure Participants	47
Screening, n=47	9.0 (5.33)
LTT, Month 3, n=46	7.7 (5.53)
LTT, Month 9, n= 46	7.7 (5.09)
LTT, Month 15, n=44	8.6 (5.97)
LTT, Month 27, n=37	8.4 (5.68)
LTT, Month 78, n=13	11.5 (6.64)

5. Secondary Outcome

Title	Unified Parkinson's Disease Rating Scale (UPDRS) Motor Examination Score (ITT Population)
Description	Two of the six UPDRS sections (Part II, Activities of Daily Living (ADL); Part III, Motor Examination) were assessed in this study. The Motor Exam has 17 items, some of which are assessed in both the left and right extremities. Each item has a choice of 5 responses that are numerically scored 0-4 (0 as the least severe, 4 as the most severe). The final score is a sum of the 17 items, with some sections requiring multiple grades assigned to each extremity, and has a value ranging from 0 (no motor impairment) to 108 (severe motor impairment).
Time Frame	Screening and Month 78

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population. Various "n" values are the result of participant attrition.

Arm/Group Title	Ropinirole XL
Arm/Group Description	Up-titration: some participants from Study 167 started at 2 milligrams (mg) ropinirole XL once daily. Then, depending on the response/tolerance of each participant, the dose was increased in 1 mg weekly increments to 4 mg, then 2 mg weekly increments up to 12 mg, and in either 2 mg or 4 mg weekly increments up to 24 mg to the clinical optimum dose. Other Study 167 participants were increased in 2 mg weekly increments up to 8 mg and then 4 mg weekly increments up to 24 mg. Study 164 particiapnts who were on an optimal dose of ropinirole XL could go straight into the long-term treatment period, and those who were receiving ropinirole IR could be switched to the corresponding XL dose. Long-term treatment: participants received study medication until market availability of ropinirole XL. After market availability, participants would undergo a 1-week down-titration period; after protocol amendment #4 approval, participants could switch directly to the market-available dose.
Measure Participants	83
Screening, n=83	22.0 (10.14)
Month 78, n=13	20.7 (7.09)

6. Secondary Outcome

Title	Unified Parkinson's Disease Rating Scale (UPDRS) Motor Examination Score (Reponder Population)
Description	Two of the six UPDRS sections (Part II, Activities of Daily Living (ADL); Part III, Motor Examination) were assessed in this study. The Motor Exam has 17 items, some of which are assessed in both the left and right extremities. Each item has a choice of 5 responses that are numerically scored 0-4 (0 as the least severe, 4 as the most severe). The final score is a sum of the 17 items, with some sections requiring multiple grades assigned to each extremity, and has a value ranging from 0 (no motor impairment) to 108 (severe motor impairment).
Time Frame	Screening and Month 78

Outcome Measure Data

Analysis Population Description

Responder Population. Various "n" values are the result of participant attrition.

Arm/Group Title	Ropinirole XL
Arm/Group Description	Up-titration: some participants from Study 167 started at 2 milligrams (mg) ropinirole XL once daily. Then, depending on the response/tolerance of each participant, the dose was increased in 1 mg weekly increments to 4 mg, then 2 mg weekly increments up to 12 mg, and in either 2 mg or 4 mg weekly increments up to 24 mg to the clinical optimum dose. Other Study 167 participants were increased in 2 mg weekly increments up to 8 mg and then 4 mg weekly increments up to 24 mg. Study 164 particiapnts who were on an optimal dose of ropinirole XL could go straight into the long-term treatment period, and those who were receiving ropinirole IR could be switched to the corresponding XL dose. Long-term treatment: participants received study medication until market availability of ropinirole XL. After market availability, participants would undergo a 1-week down-titration period; after protocol amendment #4 approval, participants could switch directly to the market-available dose.
Measure Participants	60
Screening, n=60	21.7 (9.71)
Month 78, n=13	20.7 (7.09)

7. Secondary Outcome

Title	Unified Parkinson's Disease Rating Scale (UPDRS) Motor Examination Score (Maintained Responder Population)
Description	Two of the six UPDRS sections (Part II, Activities of Daily Living (ADL); Part III, Motor Examination) were assessed in this study. The Motor Exam has 17 items, some of which are assessed in both the left and right extremities. Each item has a choice of 5 responses that are numerically scored 0-4 (0 as the least severe, 4 as the most severe). The final score is a sum of the 17 items, with some sections requiring multiple grades assigned to each extremity, and has a value ranging from 0 (no motor impairment) to 108 (severe motor impairment).
Time Frame	Screening and Month 78

Outcome Measure Data

Analysis Population Description

Maintained Responder Population. Various "n" values are the result of participant attrition.

Arm/Group Title	Ropinirole XL
Arm/Group Description	Up-titration: some participants from Study 167 started at 2 milligrams (mg) ropinirole XL once daily. Then, depending on the response/tolerance of each participant, the dose was increased in 1 mg weekly increments to 4 mg, then 2 mg weekly increments up to 12 mg, and in either 2 mg or 4 mg weekly increments up to 24 mg to the clinical optimum dose. Other Study 167 participants were increased in 2 mg weekly increments up to 8 mg and then 4 mg weekly increments up to 24 mg. Study 164 particiapnts who were on an optimal dose of ropinirole XL could go straight into the long-term treatment period, and those who were receiving ropinirole IR could be switched to the corresponding XL dose. Long-term treatment: participants received study medication until market availability of ropinirole XL. After market availability, participants would undergo a 1-week down-titration period; after protocol amendment #4 approval, participants could switch directly to the market-available dose.
Measure Participants	47
Screening, n=47	22.2 (10.11)
Month 78, n=13	20.7 (7.09)

8. Secondary Outcome

Title	Number of Participants With the Indicated Responses for CGI Global Impression (CGI-I) (ITT Population)
Description	The Clinical Global Impression (CGI) scale comprises the following three components (CGI-Severity, CGI-Improvement, Index); where only the CGI-S and CGI-I were assessed in this study. CGI-I is a global improvement scale that scores the clinician's view of the participant's global functioning prior to and after initiating a study medication from 1 (very much improved) to 7 (very much worse). 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse.
Time Frame	Week 2, Month 12, Month 78

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population. Various "n" values are the result of participant attrition.

Arm/Group Title	Ropinirole XL
Arm/Group Description	Up-titration: some participants from Study 167 started at 2 milligrams (mg) ropinirole XL once daily. Then, depending on the response/tolerance of each participant, the dose was increased in 1 mg weekly increments to 4 mg, then 2 mg weekly increments up to 12 mg, and in either 2 mg or 4 mg weekly increments up to 24 mg to the clinical optimum dose. Other Study 167 participants were increased in 2 mg weekly increments up to 8 mg and then 4 mg weekly increments up to 24 mg. Study 164 particiapnts who were on an optimal dose of ropinirole XL could go straight into the long-term treatment period, and those who were receiving ropinirole IR could be switched to the corresponding XL dose. Long-term treatment: participants received study medication until market availability of ropinirole XL. After market availability, participants would undergo a 1-week down-titration period; after protocol amendment #4 approval, participants could switch directly to the market-available dose.
Measure Participants	70
Week 2 - Very Much Improved, n=70	0 0%
Week 2 - Much Improved, n=70	2 2.4%
Week 2 - Minimally Improved, n=70	20 24.1%
Week 2 - No Change, n=70	43 51.8%
Week 2 - Minimally Worse, n=70	4 4.8%
Week 2 - Much Worse, n=70	1 1.2%
Week 2 - Very Much Worse, n=70	0 0%
Month 12 - Very Much Improved, n=69	7 8.4%
Month 12 - Much Improved, n=69	25 30.1%
Month 12 - Minimally Improved, n=69	20 24.1%
Month 12 - No Change, n=69	7 8.4%
Month 12 - Minimally Worse, n=69	8 9.6%
Month 12 - Much Worse, n=69	1 1.2%
Month 12 - Very Much Worse, n=69	0 0%
Month 78 -Very Much Improved, n=13	1 1.2%
Month 78 - Much Improved, n=13	8 9.6%
Month 78 - Minimally Improved, n=13	1 1.2%
Month 78 - No Change, n=13	1 1.2%
Month 78 - Minimally Worse, n=13	1 1.2%
Month 78 - Much Worse, n=13	0 0%
Month 78 - Very Much Worse, n=13	0 0%

9. Secondary Outcome

Title	Number of Participants With the Indicated Responses for CGI Global Impression (CGI-I) (Responder Population)
Description	The Clinical Global Impression (CGI) scale comprises the following three components (CGI-Severity, CGI-Improvement, Index); where only the CGI-S and CGI-I were assessed in this study. CGI-I is a global improvement scale that scores the clinician's view of the participant's global functioning prior to and after initiating a study medication from 1 (very much improved) to 7 (very much worse). 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse.
Time Frame	Week 2, Month 12, Month 78

Outcome Measure Data

Analysis Population Description

Responder Population. Various "n" values are the result of participant attrition.

Arm/Group Title	Ropinirole XL
Arm/Group Description	Up-titration: some participants from Study 167 started at 2 milligrams (mg) ropinirole XL once daily. Then, depending on the response/tolerance of each participant, the dose was increased in 1 mg weekly increments to 4 mg, then 2 mg weekly increments up to 12 mg, and in either 2 mg or 4 mg weekly increments up to 24 mg to the clinical optimum dose. Other Study 167 participants were increased in 2 mg weekly increments up to 8 mg and then 4 mg weekly increments up to 24 mg. Study 164 particiapnts who were on an optimal dose of ropinirole XL could go straight into the long-term treatment period, and those who were receiving ropinirole IR could be switched to the corresponding XL dose. Long-term treatment: participants received study medication until market availability of ropinirole XL. After market availability, participants would undergo a 1-week down-titration period; after protocol amendment #4 approval, participants could switch directly to the market-available dose.
Measure Participants	56
Week 2 - Very Much Improved, n=49	0 0%
Week 2 - Much Improved, n=49	2 2.4%
Week 2 - Minimally Improved, n=49	17 20.5%
Week 2 - No Change, n=49	27 32.5%
Week 2 - Minimally Worse, n=49	2 2.4%
Week 2 - Much Worse, n=49	1 1.2%
Week 2 - Very Much Worse, n=49	0 0%
Month 12 - Very Much Improved, n=56	7 8.4%
Month 12 - Much Improved, n=56	25 30.1%
Month 12 - Minimally Improved, n=56	12 14.5%
Month 12 - No Change, n=56	5 6%
Month 12 - Minimally Worse, n=56	5 6%
Month 12 - Much Worse, n=56	1 1.2%
Month 12 - Very Much Worse, n=56	0 0%
Month 78 - Very Much Improved, n=13	1 1.2%
Month 78 - Much Improved, n=13	8 9.6%
Month 78 - Minimally Improved, n=13	1 1.2%
Month 78 - No Change, n=13	1 1.2%
Month 78 - Minimally Worse, n=13	1 1.2%
Month 78 - Much Worse, n=13	0 0%
Month 78 - Very Much Worse, n=13	0 0%

10. Secondary Outcome

Title	Number of Participants With the Indicated Responses for CGI Global Impression (CGI-I) (Maintained Responder Population)
Description	The Clinical Global Impression (CGI) scale comprises the following three components (CGI-Severity, CGI-Improvement, Index); where only the CGI-S and CGI-I were assessed in this study. CGI-I is a global improvement scale that scores the clinician's view of the participant's global functioning prior to and after initiating a study medication from 1 (very much improved) to 7 (very much worse). 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse.
Time Frame	Week 2, Month 12, Month 78

Outcome Measure Data

Analysis Population Description

Maintained Responder Population. Various "n" values are the result of participant attrition.

Arm/Group Title	Ropinirole XL
Arm/Group Description	Up-titration: some participants from Study 167 started at 2 milligrams (mg) ropinirole XL once daily. Then, depending on the response/tolerance of each participant, the dose was increased in 1 mg weekly increments to 4 mg, then 2 mg weekly increments up to 12 mg, and in either 2 mg or 4 mg weekly increments up to 24 mg to the clinical optimum dose. Other Study 167 participants were increased in 2 mg weekly increments up to 8 mg and then 4 mg weekly increments up to 24 mg. Study 164 particiapnts who were on an optimal dose of ropinirole XL could go straight into the long-term treatment period, and those who were receiving ropinirole IR could be switched to the corresponding XL dose. Long-term treatment: participants received study medication until market availability of ropinirole XL. After market availability, participants would undergo a 1-week down-titration period; after protocol amendment #4 approval, participants could switch directly to the market-available dose.
Measure Participants	46
Week 2 - Very Much Improved, n=37	0 0%
Week 2 - Much Improved, n=37	2 2.4%
Week 2 - Minimally Improved, n=37	12 14.5%
Week 2 - No Change, n=37	20 24.1%
Week 2 - Minimally Worse, n=37	2 2.4%
Week 2 - Much Worse, n=37	1 1.2%
Week 2 - Very Much Worse, n=37	0 0%
Month 12 - Very Much Improved, n=46	6 7.2%
Month 12 - Much Improved, n=46	23 27.7%
Month 12 - Minimally Improved, n=46	7 8.4%
Month 12 - No Change, n=46	4 4.8%
Month 12 - Minimally Worse, n=46	4 4.8%
Month 12 - Much Worse, n=46	1 1.2%
Month 12 - Very Much Worse, n=46	0 0%
Month 78 - Very Much Improved, n=13	1 1.2%
Month 78 - Much Improved, n=13	8 9.6%
Month 78 - Minimally Improved, n=13	1 1.2%
Month 78 - No Change, n=13	1 1.2%
Month 78 - Minimally Worse, n=13	1 1.2%
Month 78 - Much Worse, n=13	0 0%
Month 78 - Very Much Worse, n=13	0 0%

Adverse Events

Time Frame	On therapy adverse events (AEs) were defined as occurring after administration of the first dose of study medication and on or before the final visit. AEs were reviewed and recorded at every visit.
Arm/Group Title	Ropinirole XL
Arm/Group Description	Up-titration: some participants from Study 167 started at 2 milligrams (mg) ropinirole XL once daily. Then, depending on the response/tolerance of each participant, the dose was increased in 1 mg weekly increments to 4 mg, then 2 mg weekly increments up to 12 mg, and in either 2 mg or 4 mg weekly increments up to 24 mg to the clinical optimum dose. Other Study 167 participants were increased in 2 mg weekly increments up to 8 mg and then 4 mg weekly increments up to 24 mg. Study 164 particiapnts who were on an optimal dose of ropinirole XL could go straight into the long-term treatment period, and those who were receiving ropinirole IR could be switched to the corresponding XL dose. Long-term treatment: participants received study medication until market availability of ropinirole XL. After market availability, participants would undergo a 1-week down-titration period; after protocol amendment #4 approval, participants could switch directly to the market-available dose.
All Cause Mortality
	Ropinirole XL
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ropinirole XL
	Affected / at Risk (%)	# Events
Total	34/83 (41%)
Blood and lymphatic system disorders
Leukocytosis	1/83 (1.2%)
Aortic aneurysm rupture	1/83 (1.2%)
Cardiac disorders
Angina pectoris	2/83 (2.4%)
Coronary heart disease	2/83 (2.4%)
Atrial flutter	1/83 (1.2%)
Sick sinus syndrome	1/83 (1.2%)
Coronary artery stenosis	1/83 (1.2%)
Gastrointestinal disorders
Ileus	1/83 (1.2%)
Gastritis	1/83 (1.2%)
Proctalgia	1/83 (1.2%)
Abdominal pain	1/83 (1.2%)
Postoerative ileus	1/83 (1.2%)
Inguinal hernia	1/83 (1.2%)
General disorders
Chest pain	4/83 (4.8%)
Non-cardiac chest pain	2/83 (2.4%)
Oedema peripheral	1/83 (1.2%)
Malaise	1/83 (1.2%)
Hepatobiliary disorders
Cholecystitis chronic	1/83 (1.2%)
Biliary colic	1/83 (1.2%)
Infections and infestations
Appendiceal abcess	1/83 (1.2%)
Postoperative wound infection	1/83 (1.2%)
Influenza	1/83 (1.2%)
Bronchitis	1/83 (1.2%)
Tracheobronchitis	1/83 (1.2%)
Urinary tract infection	1/83 (1.2%)
Urosepsis	1/83 (1.2%)
Injury, poisoning and procedural complications
Overdose	2/83 (2.4%)
Hip fracture	1/83 (1.2%)
Accident	1/83 (1.2%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	4/83 (4.8%)
Intervertebral disc protusion	2/83 (2.4%)
Muscle strain	2/83 (2.4%)
Scoliosis	2/83 (2.4%)
Femoral neck fracture	2/83 (2.4%)
Spondylisthesis	1/83 (1.2%)
Invertebral disc degeneration	1/83 (1.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	5/83 (6%)
Colon cancer	1/83 (1.2%)
Lung neoplasm	1/83 (1.2%)
Squamous cell carcinoma	1/83 (1.2%)
Breast cancer	1/83 (1.2%)
Malignant melanoma	1/83 (1.2%)
Nervous system disorders
Cerebrovascular accident	1/83 (1.2%)
Subarachnoid haemorrhage	1/83 (1.2%)
Encephalopathy	1/83 (1.2%)
Multiple sclerosis	1/83 (1.2%)
Syncope	1/83 (1.2%)
Metabolic encephalopathy	1/83 (1.2%)
Psychiatric disorders
Delirium	1/83 (1.2%)
Delusion	1/83 (1.2%)
Paranoia	1/83 (1.2%)
Obsessive-complusive disorder	1/83 (1.2%)
Mania	1/83 (1.2%)
Renal and urinary disorders
Renal failure	2/83 (2.4%)
Reproductive system and breast disorders
Pelvic pain	1/83 (1.2%)
Respiratory, thoracic and mediastinal disorders
Lung infiltration	1/83 (1.2%)
Bronchial irritiation	1/83 (1.2%)
Other (Not Including Serious) Adverse Events
	Ropinirole XL
	Affected / at Risk (%)	# Events
Total	83/83 (100%)
Blood and lymphatic system disorders
Hypertension	9/83 (10.8%)
Orthostatic hypotension	7/83 (8.4%)
Anaemia	5/83 (6%)
Cardiac disorders
Angina pectoris	5/83 (6%)
Eye disorders
Vision blurred	10/83 (12%)
Cataract	5/83 (6%)
Gastrointestinal disorders
Nausea	35/83 (42.2%)
Constipation	21/83 (25.3%)
Diarrhoea	20/83 (24.1%)
Vomiting	15/83 (18.1%)
Abdominal pain	12/83 (14.5%)
Dyspepsia	12/83 (14.5%)
Gastrointestinal reflux disease	10/83 (12%)
Dry mouth	7/83 (8.4%)
Abdominal distension	5/83 (6%)
Abdominal pain upper	5/83 (6%)
Flatulence	5/83 (6%)
General disorders
Oedema peripheral	32/83 (38.6%)
Fatigue	20/83 (24.1%)
Asthenia	9/83 (10.8%)
Chest pain	7/83 (8.4%)
Pain	6/83 (7.2%)
Infections and infestations
Nasopharyngitis	24/83 (28.9%)
Upper respiratory tract infection	15/83 (18.1%)
Bronchitis	12/83 (14.5%)
Urinary tract infection	11/83 (13.3%)
Tooth infection	9/83 (10.8%)
Influenza	7/83 (8.4%)
Herpes zoster	5/83 (6%)
Injury, poisoning and procedural complications
Fall	13/83 (15.7%)
Muscle strain	5/83 (6%)
Investigations
Weight decreased	5/83 (6%)
Metabolism and nutrition disorders
Hypercholesterolaemia	5/83 (6%)
Musculoskeletal and connective tissue disorders
Back pain	28/83 (33.7%)
Arthralgia	23/83 (27.7%)
Pain in extremity	19/83 (22.9%)
Muscle spasms	13/83 (15.7%)
Joint swelling	8/83 (9.6%)
Musculoskeletal pain	8/83 (9.6%)
Musculoskeletal stiffness	7/83 (8.4%)
Osteoarthritis	7/83 (8.4%)
Muscular weakness	5/83 (6%)
Myalgia	5/83 (6%)
Nervous system disorders
Dizziness	34/83 (41%)
Headache	26/83 (31.3%)
Somnolence	23/83 (27.7%)
Hypoaesthesia	12/83 (14.5%)
Tremor	12/83 (14.5%)
Balance disorder	6/83 (7.2%)
Cognitive disorder	5/83 (6%)
Paraesthesia	5/83 (6%)
Parkinson's disease	5/83 (6%)
Sinus headache	5/83 (6%)
Psychiatric disorders
Insomnia	22/83 (26.5%)
Depression	18/83 (21.7%)
Hallucination	14/83 (16.9%)
Anxiety	12/83 (14.5%)
Confusional state	11/83 (13.3%)
Nightmare	6/83 (7.2%)
Respiratory, thoracic and mediastinal disorders
Cough	21/83 (25.3%)
Dyspnoea	13/83 (15.7%)
Oropharyngeal pain	10/83 (12%)
Nasal congestion	5/83 (6%)
Skin and subcutaneous tissue disorders
Rash	7/83 (8.4%)
Hyperhidrosis	5/83 (6%)

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.