Onset Motor Complications Using REQUIP CR (Ropinirole Controlled-release) As Add-on Therapy To L-dopa In Parkinson's

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT00363727

Collaborator

(none)

209

Enrollment

Locations

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study evaluates how effective a new formulation of a marketed drug is in increasing the time to onset of dyskinesia (abnormal twisting, writhing movements) in patients with Parkinson's Disease who have been taking levodopa for less than 2 years.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease Parkinson Disease Dyskinesias	Drug: ropinirole controlled-release (REQUIP CR) for RLS	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

209 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Treatment

Official Title:

A Two Year Phase IIIb Randomised, Multicenter, Double-blind, SINEMET Controlled, Parallel Group, Flexible Dose Study, to Assess the Effectiveness of Controlled Release Ropinirole add-on Therapy to L-dopa at Increasing the Time to Onset of Dyskinesia in Parkinson's Disease Subjects.

Study Start Date :

Dec 1, 2003

Actual Primary Completion Date :

Jan 1, 2006

Actual Study Completion Date :

Jan 1, 2006

Outcome Measures

Primary Outcome Measures

Number of participants with time to onset of dyskinesia of treatment over 104 weeks (2 years) [Up to 2 Years]
Median time to dyskinesia could not be estimated by Kaplan-Meier methods because of the small number of events; however, number of participants with dyskinesia requiring days from the date of randomization (Day 1) to the date at which a participant has the event of interest were reported

Secondary Outcome Measures

Change from Baseline (Day 1) in united PD rating scale (UPDRS) activities of daily living (ADL) score (Part II) at Week 28 and 104 [At Weeks 28 and 104]
UPDRS assessments were conducted within a window of at least 2 hours after the previous L-dopa dose and prior to the next scheduled L-dopa dose. Participants might had been evaluated in either the "on" or "off" states and the summaries of the UPDRS motor score at each visit were produced separately for each state. Change from Baseline is the score at indicated time point minus the score at Baseline. This scale is a clinician-based rating scale used to measure motor impairments and disability. The UPDRS assesses 6 features of Parkinson's disease (PD) impairment that are evaluated using a combination of data collected by interview and participant examination. Part II had 13 questions with ADL scale ranging from 0-52 with 0 indicating no complications and higher scores indicating more severe complications. Week 104 are the records with last observation carries forward (LOCF).
Change from Baseline (Day 1) UPDRS motor score (UPDRS Part III) over period at Week 28 and Week 104 [Baseline (Day 1), Week 28, and Week 104]
UPDRS assessments were conducted within a window of at least 2 hours after the previous L-dopa dose and prior to the next scheduled L-dopa dose. Participants might had been evaluated in either the "on" or "off" states and the summaries of the UPDRS motor score at each visit were produced separately for each state. Change from Baseline is the score at indicated time point minus the score at Baseline. This scale is a clinician-based rating scale used to measure motor impairments and disability. The UPDRS assesses 6 features of Parkinson's disease (PD) impairment that are evaluated using a combination of data collected by interview and participant examination. Part III had 14 questions with ADL scale ranging from 0-56 with 0 indicating no complications and higher scores indicating more severe complications.
Number of participants with symptoms of dyskinesia over period [Upto week 106]
Responses to dyskinesia-related items on the Baseline UPDRS Part IV (Day 1) were analyzed. Part IV of the UPDRS includes 11 questions, four scored with 5-point Likert scales on which higher scores represent more severe complications.
Change from Baseline (Day 1) in fatigue score using epworth sleepiness scale (ESS) over period [Baseline (Day 1) and up to Week 104]
ESS is a brief self-administered questionnaire which asks the participant to rate on a scale of 0-3 ("would never doze" to "high chance of dozing") and was rated relative to the previous week. The scale thus indicated participants to retrospectively characterize their usual behavior in a variety of situations which were more or less soporific. The ESS score is the sum of the 8 item scores and can range from 0-24. This scale was to be administered at Baseline (Day 1), Week 28, Week 52, Week 76, Week 104. Week 104 analysis was based on LOCF. Change from Baseline (Day 1) is the value at indicated time point minus the Baseline value.
Percentage of participants with reduced PD symptom control up to 96 weeks [Up to Week 96]
Time to onset of motor fluctuations (for purposes of this study this is defined as Onset of Wearing Off) over period was analyzed as a measure of number of participants with Reduced Parkinson's Disease Symptom Control. 'Yes' response to the question "Did the participant experience a reduction in Parkinson's disease symptom control within four hours of the dose of L-dopa or the study drug " was analyzed and number of participants showing the response were recorded. The dose was adjusted as per the symptom control. No more data was reported post 96 weeks.
Percentage of participants with a score of "much improved" or "very much improved" on the clinical global impression of improvement (CGI -I) up to 52 weeks [Up to 52 weeks]
The CGI-I scale allows the Investigator to rate the participant's total improvement since beginning the treatment (Baseline/ Day 1). The scale was rated from 1-7 (1="very much improved", 7= "very much worse") from Week 1 onwards will the first year (and at early withdrawal, if applicable).
Mean change from Baseline (Day 1) in PD quality of life score (PDQ39) scale over period [Up to 104 weeks]
Week 104 analysis was LOCF analysis. Change from Baseline (Day 1) is the value at indicated time point minus the value at Baseline.
Mini mental status examination (MMSE) score status at screening and Week 104 [Screening and Week 104]
MMSE is a brief, easily administered mental status examination which is highly reliable and a valid instrument for detecting and tracking the progression of cognitive impairment associated with neurogenerative diseases. The MMSE scale consists of 11 items, with total maximum items scores ranging from 1 to 5. The total maximum score for the MMSE is calculated as the sum of scores for each of the 11 items that is 30, representing the highest level of mental functioning.
Change from Baseline (Day 1) in total score on the beck depression inventory (BDI) over period [Baseline (Day 1) and up to Week 104]
BDI version II (BDI-II) is a 21-item questionnaire that is completed by the participant (the recommended method of use is by assisted self-rating). The BDI included 21 ordered groups of statements from which participants selected the most appropriate description for themselves. Nineteen groups allow a choice from four statements and two sets allow a choice from seven statements. Each group of statements was scored based on the relative severity of the statement chosen, with higher scores representing greater severity. The total BDI score is the sum of scores from the 21 statement groups; total ranging from 0-69, with high values representing the more severe depression.
Change from Baseline (Day 1) in night-time quality of sleep scores of the PD sleep scale (PDSS) over period [Week 28, 52, 76, and 104]
PDSS scale consists of a series of 15 visual analogue scales (VAS) addressing commonly reported symptoms associated with sleep disturbance in PD. The participant or caregiver (by proxy) completed the scale based on their experiences in the past week. The severity of symptoms is reported by marking a cross on each 10 centimeters (cm) VAS line (labeled from worst to best state). Responses were quantified by measuring the distance along each line where the cross was placed. Thus, scores for each item ranged from 0 (symptom severe and always experienced) to 10 (symptom free). The maximum cumulative score for the PDSS was 150 (participant is free of all symptoms); total score was made of cumulative distance scores from fifteen 10 cm lines. Change from Baseline (Day 1) is the value at indicated time point minus the baseline value. Analysis at Week 104 was LOCF observation.
Percentage of participants of genes variants of interest with and without dyskinesia over period [Up to Week 104]
The percentage of randomized participants who consented to genotype sampling and for whom a blood sample was actually collected were summarized; however, no conclusions were drawn, since the pharmacogenetic analysis of the dyskinesia events was not undertaken.

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Must be on 600mg or less of levodopa therapy for two years or less.
Must be on a stable dose of levodopa therapy for at least 4 weeks prior to screening.

Exclusion Criteria:

Current or past history of Dyskinesia.
State of dementia or have a MMSE score < 26 at screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Anniston	Alabama	United States	36207
2	GSK Investigational Site	Birmingham	Alabama	United States	35216
3	GSK Investigational Site	Birmingham	Alabama	United States	35294
4	GSK Investigational Site	Phoenix	Arizona	United States	85006
5	GSK Investigational Site	Sun City	Arizona	United States	85351
6	GSK Investigational Site	Tucson	Arizona	United States	85712
7	GSK Investigational Site	La Jolla	California	United States	92037
8	GSK Investigational Site	LaJolla	California	United States	92037
9	GSK Investigational Site	Los Angeles	California	United States	90033
10	GSK Investigational Site	Newport Beach	California	United States	92660
11	GSK Investigational Site	Oxnard	California	United States	93030
12	GSK Investigational Site	San Jose	California	United States	95126
13	GSK Investigational Site	Walnut Creek	California	United States	94596
14	GSK Investigational Site	Boulder	Colorado	United States	80304
15	GSK Investigational Site	Danbury	Connecticut	United States	06810
16	GSK Investigational Site	Newark	Delaware	United States	19713
17	GSK Investigational Site	Boca Raton	Florida	United States	33486
18	GSK Investigational Site	Fort Lauderdale	Florida	United States	33145
19	GSK Investigational Site	Gainesville	Florida	United States	32611
20	GSK Investigational Site	Miami	Florida	United States	33143
21	GSK Investigational Site	Palm Beach Gardens	Florida	United States	33410
22	GSK Investigational Site	Pembroke Pines	Florida	United States	33026
23	GSK Investigational Site	Port Charlotte	Florida	United States	33952
24	GSK Investigational Site	Tampa	Florida	United States	33606
25	GSK Investigational Site	Tampa	Florida	United States	33612
26	GSK Investigational Site	Augusta	Georgia	United States	30912
27	GSK Investigational Site	Austell	Georgia	United States	30106
28	GSK Investigational Site	Columbus	Georgia	United States	31901
29	GSK Investigational Site	Decatur	Georgia	United States	30033
30	GSK Investigational Site	Boise	Idaho	United States	83702
31	GSK Investigational Site	Chicago	Illinois	United States	60611
32	GSK Investigational Site	Chicago	Illinois	United States	60637
33	GSK Investigational Site	Hoffman Estates	Illinois	United States	60194
34	GSK Investigational Site	Northbrook	Illinois	United States	60062
35	GSK Investigational Site	Des Moines	Iowa	United States	50309-1426
36	GSK Investigational Site	Kansas City	Kansas	United States	66160
37	GSK Investigational Site	Elkridge	Maryland	United States	21075
38	GSK Investigational Site	South Weymouth	Massachusetts	United States	2190
39	GSK Investigational Site	West Yarmouth	Massachusetts	United States	02673
40	GSK Investigational Site	Bingham Farms	Michigan	United States	48025
41	GSK Investigational Site	Grand Rapids	Michigan	United States	49503
42	GSK Investigational Site	Traverse City	Michigan	United States	49684
43	GSK Investigational Site	Las Vegas	Nevada	United States	89109
44	GSK Investigational Site	Edison	New Jersey	United States	08818
45	GSK Investigational Site	Albany	New York	United States	12205
46	GSK Investigational Site	Amherst	New York	United States	14226
47	GSK Investigational Site	Rochester	New York	United States	14603
48	GSK Investigational Site	Asheville	North Carolina	United States	28801
49	GSK Investigational Site	Chapel Hill	North Carolina	United States	27516
50	GSK Investigational Site	Raleigh	North Carolina	United States	27607
51	GSK Investigational Site	Winston-Salem	North Carolina	United States	27103
52	GSK Investigational Site	Cincinnati	Ohio	United States	45267-0525
53	GSK Investigational Site	Eugene	Oregon	United States	97401
54	GSK Investigational Site	Medford	Oregon	United States	97504-8456
55	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19104
56	GSK Investigational Site	Austin	Texas	United States	78756
57	GSK Investigational Site	Dallas	Texas	United States	75231
58	GSK Investigational Site	Dallas	Texas	United States	75235
59	GSK Investigational Site	Houston	Texas	United States	77030
60	GSK Investigational Site	Houston	Texas	United States	77081
61	GSK Investigational Site	Lubbock	Texas	United States	79410
62	GSK Investigational Site	San Antonio	Texas	United States	78229
63	GSK Investigational Site	Alexandria	Virginia	United States	22311
64	GSK Investigational Site	Richmond	Virginia	United States	23226
65	GSK Investigational Site	Roanoke	Virginia	United States	24014
66	GSK Investigational Site	Kirkland	Washington	United States	98034
67	GSK Investigational Site	Seattle	Washington	United States	98101
68	GSK Investigational Site	Tacoma	Washington	United States	98405
69	GSK Investigational Site	Charleston	West Virginia	United States	25301
70	GSK Investigational Site	Madison	Wisconsin	United States	53715