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

Parkinson Disease Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00363727
• Other study ID #: 101468/228
• Status: Completed
• Phase: Phase 3
• First received: August 7, 2006
• Last updated: January 16, 2017
• Start date: December 2003
• Est. completion date: January 2006

Study information

• Verified date: January 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 209
• Est. completion date: January 2006
• Est. primary completion date: January 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Dyskinesias
• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• ropinirole controlled-release (REQUIP CR) for RLS

Locations

Country	Name	City	State
United States	GSK Investigational Site	Albany	New York
United States	GSK Investigational Site	Alexandria	Virginia
United States	GSK Investigational Site	Amherst	New York
United States	GSK Investigational Site	Anniston	Alabama
United States	GSK Investigational Site	Asheville	North Carolina
United States	GSK Investigational Site	Augusta	Georgia
United States	GSK Investigational Site	Austell	Georgia
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Bingham Farms	Michigan
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Boca Raton	Florida
United States	GSK Investigational Site	Boise	Idaho
United States	GSK Investigational Site	Boulder	Colorado
United States	GSK Investigational Site	Chapel Hill	North Carolina
United States	GSK Investigational Site	Charleston	West Virginia
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Columbus	Georgia
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Danbury	Connecticut
United States	GSK Investigational Site	Decatur	Georgia
United States	GSK Investigational Site	Des Moines	Iowa
United States	GSK Investigational Site	Edison	New Jersey
United States	GSK Investigational Site	Elkridge	Maryland
United States	GSK Investigational Site	Eugene	Oregon
United States	GSK Investigational Site	Fort Lauderdale	Florida
United States	GSK Investigational Site	Gainesville	Florida
United States	GSK Investigational Site	Grand Rapids	Michigan
United States	GSK Investigational Site	Hoffman Estates	Illinois
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Kansas City	Kansas
United States	GSK Investigational Site	Kirkland	Washington
United States	GSK Investigational Site	La Jolla	California
United States	GSK Investigational Site	LaJolla	California
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Lubbock	Texas
United States	GSK Investigational Site	Madison	Wisconsin
United States	GSK Investigational Site	Medford	Oregon
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Newark	Delaware
United States	GSK Investigational Site	Newport Beach	California
United States	GSK Investigational Site	Northbrook	Illinois
United States	GSK Investigational Site	Oxnard	California
United States	GSK Investigational Site	Palm Beach Gardens	Florida
United States	GSK Investigational Site	Pembroke Pines	Florida
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Port Charlotte	Florida
United States	GSK Investigational Site	Raleigh	North Carolina
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Roanoke	Virginia
United States	GSK Investigational Site	Rochester	New York
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Jose	California
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	South Weymouth	Massachusetts
United States	GSK Investigational Site	Sun City	Arizona
United States	GSK Investigational Site	Tacoma	Washington
United States	GSK Investigational Site	Tampa	Florida
United States	GSK Investigational Site	Tampa	Florida
United States	GSK Investigational Site	Traverse City	Michigan
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Walnut Creek	California
United States	GSK Investigational Site	West Yarmouth	Massachusetts
United States	GSK Investigational Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United States, 

References & Publications (2)

R Watts, K Sethi, R Pahwa, B Adams, N Earl. Ropinirole 24-hour prolonged release delays the onset of dyskinesia Compared with carbidopa/levodopa in patients with Parkinson's disease treated with levodopa. Eur J Neurol. 2007;14 (Issue s1):1-355 .

R Watts, K Sethi, R Pahwa, B Adams, N Earl. Ropinirole 24-hour prolonged release delays the onset of dyskinesia compared with carbidopa/levodopa in patients with Parkinson's disease treated with levodopa. Movement Disorders. 2007;22 (Suppl.16):S94/307.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with time to onset of dyskinesia of treatment over 104 weeks (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	Up to 2 Years
Secondary	Change from Baseline (Day 1) in united PD rating scale (UPDRS) activities of daily living (ADL) score (Part II) at Week 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).	At Weeks 28 and 104
Secondary	Change from Baseline (Day 1) UPDRS motor score (UPDRS Part III) over period at 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.	Baseline (Day 1), Week 28, and Week 104
Secondary	Number of participants with symptoms of dyskinesia over period	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.	Upto week 106
Secondary	Change from Baseline (Day 1) in fatigue score using epworth sleepiness scale (ESS) over period	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.	Baseline (Day 1) and up to Week 104
Secondary	Percentage of participants with reduced PD symptom control up to 96 weeks	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.	Up to Week 96
Secondary	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	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).	Up to 52 weeks
Secondary	Mean change from Baseline (Day 1) in PD quality of life score (PDQ39) scale over period	Week 104 analysis was LOCF analysis. Change from Baseline (Day 1) is the value at indicated time point minus the value at Baseline.	Up to 104 weeks
Secondary	Mini mental status examination (MMSE) score status at 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.	Screening and Week 104
Secondary	Change from Baseline (Day 1) in total score on the beck depression inventory (BDI) over period	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.	Baseline (Day 1) and up to Week 104
Secondary	Change from Baseline (Day 1) in night-time quality of sleep scores of the PD sleep scale (PDSS) over period	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.	Week 28, 52, 76, and 104
Secondary	Percentage of participants of genes variants of interest with and without dyskinesia over period	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.	Up to Week 104

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