Long-Term Safety Of Ropinirole XR In Patients With Restless Legs Syndrome

A 52-Week, Open-Label Study to Assess the Long-Term Safety of Ropinirole Extended Release (XR) in Patients With Restless Legs Syndrome (RLS)

The primary objective of this study is to assess the safety and tolerability of ropinirole XR in the long-term treatment (up to 52 weeks)of adults with RLS.

Study Overview

• Status: Completed
• Conditions: Restless Legs Syndrome
• Intervention / Treatment: Drug: Ropinirole Extended Release (XR)

• Study Type: Interventional
• Enrollment (Actual): 450
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Coquitlam, British Columbia, Canada, V3K 3P4
      • GSK Investigational Site
    • Langley, British Columbia, Canada, V3A 4H9
      • GSK Investigational Site
  • Ontario
    • Ajax, Ontario, Canada, L1S 2J5
      • GSK Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H2T 2N6
      • GSK Investigational Site
    • Sherbrooke, Quebec, Canada, J1H 1Z1
      • GSK Investigational Site
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4P 0W5
      • GSK Investigational Site
• United States
  • Alabama
    • Alabaster, Alabama, United States, 35007
      • GSK Investigational Site
    • Jasper, Alabama, United States, 35501
      • GSK Investigational Site
  • Arizona
    • Mesa, Arizona, United States, 85201
      • GSK Investigational Site
    • Phoenix, Arizona, United States, 85050
      • GSK Investigational Site
    • Sun City, Arizona, United States, 85351
      • GSK Investigational Site
  • California
    • Laguna Hills, California, United States, 82653
      • GSK Investigational Site
    • Northridge, California, United States, 91325
      • GSK Investigational Site
    • Oxnard, California, United States, 93030
      • GSK Investigational Site
    • Pasadena, California, United States, 91106
      • GSK Investigational Site
    • Redondo Beach, California, United States, 90277
      • GSK Investigational Site
    • Reseda, California, United States, 91355
      • GSK Investigational Site
    • San Diego, California, United States, 92103
      • GSK Investigational Site
    • Santa Monica, California, United States, 90404
      • GSK Investigational Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • GSK Investigational Site
    • Denver, Colorado, United States, 80212
      • GSK Investigational Site
    • Wheat Ridge, Colorado, United States, 80033
      • GSK Investigational Site
  • Florida
    • Boca Raton, Florida, United States, 33486
      • GSK Investigational Site
    • Largo, Florida, United States, 33773
      • GSK Investigational Site
    • St. Petersburg, Florida, United States, 33701
      • GSK Investigational Site
    • Stuart, Florida, United States, 34996
      • GSK Investigational Site
    • Tampa, Florida, United States, 33609
      • GSK Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • GSK Investigational Site
    • Atlanta, Georgia, United States, 30338
      • GSK Investigational Site
    • Austell, Georgia, United States, 30106
      • GSK Investigational Site
    • Dawsonville, Georgia, United States, 30534
      • GSK Investigational Site
    • Macon, Georgia, United States, 31201
      • GSK Investigational Site
    • Woodstock, Georgia, United States, 30189
      • GSK Investigational Site
  • Illinois
    • Oak Brook, Illinois, United States, 60523
      • GSK Investigational Site
  • Kansas
    • Lenexa, Kansas, United States, 66214
      • GSK Investigational Site
    • Topeka, Kansas, United States, 66606
      • GSK Investigational Site
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • GSK Investigational Site
  • Massachusetts
    • Springfield, Massachusetts, United States, 01104
      • GSK Investigational Site
  • Michigan
    • Bingham Farms, Michigan, United States, 48025
      • GSK Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • GSK Investigational Site
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08003
      • GSK Investigational Site
    • Toms River, New Jersey, United States, 08755
      • GSK Investigational Site
  • New York
    • Endwell, New York, United States, 13760
      • GSK Investigational Site
    • New York, New York, United States, 10021
      • GSK Investigational Site
    • Schenectady, New York, United States, 12308
      • GSK Investigational Site
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • GSK Investigational Site
    • Raleigh, North Carolina, United States, 27607
      • GSK Investigational Site
  • Ohio
    • Cleveland, Ohio, United States, 44130
      • GSK Investigational Site
    • Columbus, Ohio, United States, 43232
      • GSK Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • GSK Investigational Site
  • Oregon
    • Medford, Oregon, United States, 97504-8456
      • GSK Investigational Site
    • Portland, Oregon, United States, 97210
      • GSK Investigational Site
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • GSK Investigational Site
    • Mount Pleasant, South Carolina, United States, 29464
      • GSK Investigational Site
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • GSK Investigational Site
  • Texas
    • Dallas, Texas, United States, 75231
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78229
      • GSK Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84121
      • GSK Investigational Site
    • Salt Lake City, Utah, United States, 84107
      • GSK Investigational Site
  • Virginia
    • Alexandria, Virginia, United States, 22311
      • GSK Investigational Site
    • Charlottesville, Virginia, United States, 22911
      • GSK Investigational Site
  • Washington
    • Spokane, Washington, United States, 99204
      • GSK Investigational Site
    • Tacoma, Washington, United States, 98405
      • GSK Investigational Site
    • Walla Walla, Washington, United States, 99362
      • GSK Investigational Site
    • Wenatchee, Washington, United States, 98801
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• A subject will be eligible for inclusion in this study only if all of the following criteria apply:

• Subjects in North America ≥18 years of age who

  1. Have successfully completed one of the following parent studies: 101468/205, ROX104805; OR
  2. Have a diagnosis of primary RLS using the International RLS Study Group (IRSSG) Diagnostic Criteria (Appendix 10), experience RLS symptoms during both the evening (before 8 PM) and night-time, and have a total score ≥15 on the IRLS Rating Scale at Baseline. Subjects must have a history of a minimum of 20 evenings/nights of RLS episodes per month (e.g., any combination of evenings and/or nights for ≥ 20 days). During Screening/Washout, RLS symptoms must be present for at least 4 of 7 evenings/nights immediately prior to the Baseline Visit (e.g., any combination of evenings and/or nights for ≥ 4 days).
• Subjects must give written informed consent prior to any specific study procedures.

Exclusion Criteria:

• Subjects who have any medical conditions which, in the opinion of the investigator, could affect efficacy assessments or clinically significant or unstable medical conditions that present a safety concern. These may include, but are not limited to the following disorders: diabetes, peripheral neuropathy, rheumatoid arthritis, fibromyalgia syndrome, symptomatic orthostatic hypotension, severe cardiovascular disease, hepatic or renal failure, pleuro-pulmonary fibrosis.
• Subjects having clinically significant abnormal laboratory or ECG findings not resolved at time of baseline examinations. Abnormal 12-lead ECG findings include, but are not limited to the following: myocardial ischemia, clinically significant conduction abnormalities, or clinically significant arrhythmias.
• Subjects with a diastolic blood pressure ≥ 110mmHg or ≤ 50mmHg or systolic blood pressure ≥ 180mmHg or ≤ 90mmHg at the Screening or Baseline visit.

• Subjects with a history of augmentation and/or end-of-dose rebound symptoms.

  • Augmentation is defined as RLS symptoms that occurred while on treatment and occur ≥ 2 hours earlier than they did before, symptoms which are more severe than when not treated, symptoms which start after less time at rest than they did before treatment, or symptoms which involve other parts of the body, such as the arms or trunk.
  • End-of-dose rebound is defined as a re-emergence of RLS symptoms in the early morning the day after taking the dose of RLS medication.
• Subjects who have exhibited intolerance to ropinirole.

• For subjects entering Study 206, certain medications must be discontinued prior to entering the study. The following medications are prohibited for the duration of the study period which is up to and including the Follow-up visit:

  ·dopamine agonists (including ropinirole immediate release formulation), dopamine antagonists (e.g., typical neuroleptics, metoclopramide), levodopa/carbidopa The minimum discontinuation period is generally 5 half-lives or 7 consecutive evening/nights medication-free, prior to baseline, whichever is the longer period. If the subject will require longer than 2 weeks following the Follow-up visit of the parent study to complete the washout, GSK must be consulted for further instructions.

• Other medications, including those with partial dopaminergic activity (e.g., atypical antipsychotics, certain antidepressants such as bupropion, tricyclic antidepressants and monoamine oxidase inhibitors) may have additive activity with ropinirole and should be used with caution in patients taking ropinirole. For patients on stable doses, these agents may be permitted; however, it is recommended that the dose of the medication remain stable throughout the duration of the study.
• Night workers or any others whose sleeping habits are incompatible with the study design, or who would be required to make significant changes to their bedtime during the course of the study.
• Women who have a positive pregnancy test.
• Women of child-bearing potential who are not practicing a clinically accepted method of contraception such as oral contraception, surgical sterilization, IUD, diaphragm in conjunction with spermicidal foam and condom on the male partner, or systemic contraception (e.g. Norplant).

The following exclusion criteria must be assessed at Study 206 Screen/Baseline for subjects who are not rolling in following completion of Study 101468/205 or ROX104805:

• Subjects who suffer from a primary sleep disorder other than RLS that may significantly affect the symptoms of RLS (e.g., narcolepsy, sleep terror disorder, sleepwalking disorder, breathing related sleep disorder).
• Subjects diagnosed with movement disorders (e.g., Parkinson's disease, dyskinesias, and dystonias).
• Signs of secondary RLS (e.g., end stage renal disease, iron deficient anemia or pregnancy at Baseline Visit)
• Subjects requiring treatment of daytime RLS symptoms (daytime defined as 7:00 AM until 5:00 PM).
• Subjects with a history of alcohol or substance abuse within the past year.
• Subjects who, in the opinion of the investigator, would be non-compliant with the visit schedule or other study procedures
• Participation in any clinical drug or device trial (other than Study 101468/205 or ROX104805) in the one month prior to the Baseline Visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open Label; All subjects will receive ropinirole XR in this study. The total daily dose range of ropinirole XR will be 0.5mg to 6.0mg daily	Drug: Ropinirole Extended Release (XR); Dose range of Ropinirole XR of 0.5mg to 6.0mg daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence/severity of adverse events Changes in vital signs Labs ECG Assessment of augmentation and rebound (worsening of RLS symptoms).	Up to 52 Weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in IRLS Rating Scale total score CGI Scale scores Medical Outcomes Study Sleep Scale scores Other subject-reported health outcomes.	Up to 52 Weeks
Incidence and severity of adverse events.	Up to 52 Weeks
Changes in vital signs (blood pressure and pulse) and weight.	Up to 52 Weeks
Changes in laboratory assessments (hematology and clinical chemistry).	Up to 52 Weeks
Changes in electrocardiogram (ECG) parameters.	Up to 52 Weeks
Assessment of augmentation.	Up to 52 Weeks
Assessment of rebound.	Up to 52 Weeks
Change from baseline in the IRLS Rating Scale total score at Week 52 LOCF (last observation carried forward).	Up to 52 Weeks
Proportion of subjects with a score of much improved (2) or very much improved (1) on CGI-I at Week 52 LOCF.	Up to 52 Weeks
CGI Severity of Illness (CGI-S) at Week 52 LOCF.	Up to 52 Weeks
Change from baseline in the domains of the Medical Outcomes Study (MOS-12) Sleep Scale at Week 52 LOCF.	Up to 52 Weeks
Change from baseline in the overall life impact score of the RLS Quality of Life Questionnaire at Week 52 LOCF.	Up to 52 Weeks
Change from baseline in the anxiety and depression domains of the Hospital Anxiety and Depression (HADS) Scale at Week 52 LOCF.	Up to 52 Weeks
Change from baseline in the total score and domains of the Profile of Mood States (POMS) Scale Short Form at Week 52 LOCF.	Up to 52 Weeks
Change from baseline in the parameters for the work Productivity and Activity Impairment - Specific Health Problem (WPAI-SHP) Questionnaire at Week 52 LOCF.	Up to 52 Weeks
Proportion of subjects satisfied with their treatment at Week 52 LOCF.	Up to 52 Weeks

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• C Hill-Zabala, R Bogan, D Lee, M Lomax. A 52-week open-label study to assess the long-term tolerability of Ropinirole CR Extended Release Tablets in subjects with Restless Legs Syndrome (RLS). 12th International Congress of Parkinson's Disease and Movement Disorders, Chicago, IL, June 22-26, 2008 (abstract 1112).

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: July 20, 2006
• First Submitted That Met QC Criteria: July 20, 2006
• First Posted (Estimate): July 24, 2006

Study Record Updates

• Last Update Posted (Estimate): October 28, 2016
• Last Update Submitted That Met QC Criteria: October 27, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Restless Legs Syndrome; Ropinirole; RLS
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Dyskinesias; Psychomotor Disorders; Parasomnias; Syndrome; Psychomotor Agitation; Restless Legs Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agonists; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Ropinirole
• Other Study ID Numbers: 101468/206

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. Statistical Analysis Plan
   Information identifier: 101468/206
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: 101468/206
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 101468/206
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Dataset Specification
   Information identifier: 101468/206
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 101468/206
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Annotated Case Report Form
   Information identifier: 101468/206
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: 101468/206
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register