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

January 16, 2017 updated by: GlaxoSmithKline

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.

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

209

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Alabama
      • Anniston, Alabama, United States, 36207
        • GSK Investigational Site
      • Birmingham, Alabama, United States, 35294
        • GSK Investigational Site
      • Birmingham, Alabama, United States, 35216
        • GSK Investigational Site
    • Arizona
      • Phoenix, Arizona, United States, 85006
        • GSK Investigational Site
      • Sun City, Arizona, United States, 85351
        • GSK Investigational Site
      • Tucson, Arizona, United States, 85712
        • GSK Investigational Site
    • California
      • La Jolla, California, United States, 92037
        • GSK Investigational Site
      • LaJolla, California, United States, 92037
        • GSK Investigational Site
      • Los Angeles, California, United States, 90033
        • GSK Investigational Site
      • Newport Beach, California, United States, 92660
        • GSK Investigational Site
      • Oxnard, California, United States, 93030
        • GSK Investigational Site
      • San Jose, California, United States, 95126
        • GSK Investigational Site
      • Walnut Creek, California, United States, 94596
        • GSK Investigational Site
    • Colorado
      • Boulder, Colorado, United States, 80304
        • GSK Investigational Site
    • Connecticut
      • Danbury, Connecticut, United States, 06810
        • GSK Investigational Site
    • Delaware
      • Newark, Delaware, United States, 19713
        • GSK Investigational Site
    • Florida
      • Boca Raton, Florida, United States, 33486
        • GSK Investigational Site
      • Fort Lauderdale, Florida, United States, 33145
        • GSK Investigational Site
      • Gainesville, Florida, United States, 32611
        • GSK Investigational Site
      • Miami, Florida, United States, 33143
        • GSK Investigational Site
      • Palm Beach Gardens, Florida, United States, 33410
        • GSK Investigational Site
      • Pembroke Pines, Florida, United States, 33026
        • GSK Investigational Site
      • Port Charlotte, Florida, United States, 33952
        • GSK Investigational Site
      • Tampa, Florida, United States, 33612
        • GSK Investigational Site
      • Tampa, Florida, United States, 33606
        • GSK Investigational Site
    • Georgia
      • Augusta, Georgia, United States, 30912
        • GSK Investigational Site
      • Austell, Georgia, United States, 30106
        • GSK Investigational Site
      • Columbus, Georgia, United States, 31901
        • GSK Investigational Site
      • Decatur, Georgia, United States, 30033
        • GSK Investigational Site
    • Idaho
      • Boise, Idaho, United States, 83702
        • GSK Investigational Site
    • Illinois
      • Chicago, Illinois, United States, 60637
        • GSK Investigational Site
      • Chicago, Illinois, United States, 60611
        • GSK Investigational Site
      • Hoffman Estates, Illinois, United States, 60194
        • GSK Investigational Site
      • Northbrook, Illinois, United States, 60062
        • GSK Investigational Site
    • Iowa
      • Des Moines, Iowa, United States, 50309-1426
        • GSK Investigational Site
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • GSK Investigational Site
    • Maryland
      • Elkridge, Maryland, United States, 21075
        • GSK Investigational Site
    • Massachusetts
      • South Weymouth, Massachusetts, United States, 2190
        • GSK Investigational Site
      • West Yarmouth, Massachusetts, United States, 02673
        • GSK Investigational Site
    • Michigan
      • Bingham Farms, Michigan, United States, 48025
        • GSK Investigational Site
      • Grand Rapids, Michigan, United States, 49503
        • GSK Investigational Site
      • Traverse City, Michigan, United States, 49684
        • GSK Investigational Site
    • Nevada
      • Las Vegas, Nevada, United States, 89109
        • GSK Investigational Site
    • New Jersey
      • Edison, New Jersey, United States, 08818
        • GSK Investigational Site
    • New York
      • Albany, New York, United States, 12205
        • GSK Investigational Site
      • Amherst, New York, United States, 14226
        • GSK Investigational Site
      • Rochester, New York, United States, 14603
        • GSK Investigational Site
    • North Carolina
      • Asheville, North Carolina, United States, 28801
        • GSK Investigational Site
      • Chapel Hill, North Carolina, United States, 27516
        • GSK Investigational Site
      • Raleigh, North Carolina, United States, 27607
        • GSK Investigational Site
      • Winston-Salem, North Carolina, United States, 27103
        • GSK Investigational Site
    • Ohio
      • Cincinnati, Ohio, United States, 45267-0525
        • GSK Investigational Site
    • Oregon
      • Eugene, Oregon, United States, 97401
        • GSK Investigational Site
      • Medford, Oregon, United States, 97504-8456
        • GSK Investigational Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • GSK Investigational Site
    • Texas
      • Austin, Texas, United States, 78756
        • GSK Investigational Site
      • Dallas, Texas, United States, 75231
        • GSK Investigational Site
      • Dallas, Texas, United States, 75235
        • GSK Investigational Site
      • Houston, Texas, United States, 77030
        • GSK Investigational Site
      • Houston, Texas, United States, 77081
        • GSK Investigational Site
      • Lubbock, Texas, United States, 79410
        • GSK Investigational Site
      • San Antonio, Texas, United States, 78229
        • GSK Investigational Site
    • Virginia
      • Alexandria, Virginia, United States, 22311
        • GSK Investigational Site
      • Richmond, Virginia, United States, 23226
        • GSK Investigational Site
      • Roanoke, Virginia, United States, 24014
        • GSK Investigational Site
    • Washington
      • Kirkland, Washington, United States, 98034
        • GSK Investigational Site
      • Seattle, Washington, United States, 98101
        • GSK Investigational Site
      • Tacoma, Washington, United States, 98405
        • GSK Investigational Site
    • West Virginia
      • Charleston, West Virginia, United States, 25301
        • GSK Investigational Site
    • Wisconsin
      • Madison, Wisconsin, United States, 53715
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with time to onset of dyskinesia of treatment over 104 weeks (2 years)
Time Frame: 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
Up to 2 Years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Baseline (Day 1) in united PD rating scale (UPDRS) activities of daily living (ADL) score (Part II) at Week 28 and 104
Time Frame: 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).
At Weeks 28 and 104
Change from Baseline (Day 1) UPDRS motor score (UPDRS Part III) over period at Week 28 and Week 104
Time Frame: 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.
Baseline (Day 1), Week 28, and Week 104
Number of participants with symptoms of dyskinesia over period
Time Frame: 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.
Upto week 106
Change from Baseline (Day 1) in fatigue score using epworth sleepiness scale (ESS) over period
Time Frame: 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.
Baseline (Day 1) and up to Week 104
Percentage of participants with reduced PD symptom control up to 96 weeks
Time Frame: 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.
Up to Week 96
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
Time Frame: 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
Mean change from Baseline (Day 1) in PD quality of life score (PDQ39) scale over period
Time Frame: 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.
Up to 104 weeks
Mini mental status examination (MMSE) score status at screening and Week 104
Time Frame: 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
Change from Baseline (Day 1) in total score on the beck depression inventory (BDI) over period
Time Frame: 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.
Baseline (Day 1) and up to Week 104
Change from Baseline (Day 1) in night-time quality of sleep scores of the PD sleep scale (PDSS) over period
Time Frame: 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.
Week 28, 52, 76, and 104
Percentage of participants of genes variants of interest with and without dyskinesia over period
Time Frame: 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.
Up to Week 104

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • 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.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2003

Primary Completion (Actual)

January 1, 2006

Study Completion (Actual)

January 1, 2006

Study Registration Dates

First Submitted

August 7, 2006

First Submitted That Met QC Criteria

August 11, 2006

First Posted (Estimate)

August 15, 2006

Study Record Updates

Last Update Posted (Estimate)

January 18, 2017

Last Update Submitted That Met QC Criteria

January 16, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

  1. Individual Participant Data Set
    Information identifier: 101468/228
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  2. Annotated Case Report Form
    Information identifier: 101468/228
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  3. Clinical Study Report
    Information identifier: 101468/228
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  4. Statistical Analysis Plan
    Information identifier: 101468/228
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  5. Dataset Specification
    Information identifier: 101468/228
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  6. Study Protocol
    Information identifier: 101468/228
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register
  7. Informed Consent Form
    Information identifier: 101468/228
    Information comments: For additional information about this study please refer to the GSK Clinical Study Register

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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