Clinical trial NCT00355641: Long-Term Safety Of Ropinirole XR In Patients With Restless Legs Syndrome
Official title: A 52-Week, Open-Label Study to Assess the Long-Term Safety of Ropinirole Extended Release (XR) in Patients With Restless Legs Syndrome (RLS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Restless Legs Syndrome
Keywords: Ropinirole
Restless Legs Syndrome
RLS
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-07-24
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Incidence/severity of adverse events Changes in vital signs Labs ECG Assessment of augmentation and rebound (worsening of RLS symptoms).
timeFrame: Up to 52 Weeks
Secondary outcomes:
measure: Change from baseline in IRLS Rating Scale total score CGI Scale scores Medical Outcomes Study Sleep Scale scores Other subject-reported health outcomes.
timeFrame: Up to 52 Weeks
measure: Incidence and severity of adverse events.
timeFrame: Up to 52 Weeks
measure: Changes in vital signs (blood pressure and pulse) and weight.
timeFrame: Up to 52 Weeks
measure: Changes in laboratory assessments (hematology and clinical chemistry).
timeFrame: Up to 52 Weeks
measure: Changes in electrocardiogram (ECG) parameters.
timeFrame: Up to 52 Weeks
measure: Assessment of augmentation.
timeFrame: Up to 52 Weeks
measure: Assessment of rebound.
timeFrame: Up to 52 Weeks
measure: Change from baseline in the IRLS Rating Scale total score at Week 52 LOCF (last observation carried forward).
timeFrame: Up to 52 Weeks
measure: Proportion of subjects with a score of much improved (2) or very much improved (1) on CGI-I at Week 52 LOCF.
timeFrame: Up to 52 Weeks
measure: CGI Severity of Illness (CGI-S) at Week 52 LOCF.
timeFrame: Up to 52 Weeks
measure: Change from baseline in the domains of the Medical Outcomes Study (MOS-12) Sleep Scale at Week 52 LOCF.
timeFrame: Up to 52 Weeks
measure: Change from baseline in the overall life impact score of the RLS Quality of Life Questionnaire at Week 52 LOCF.
timeFrame: Up to 52 Weeks
measure: Change from baseline in the anxiety and depression domains of the Hospital Anxiety and Depression (HADS) Scale at Week 52 LOCF.
timeFrame: Up to 52 Weeks
measure: Change from baseline in the total score and domains of the Profile of Mood States (POMS) Scale Short Form at Week 52 LOCF.
timeFrame: Up to 52 Weeks
measure: Change from baseline in the parameters for the work Productivity and Activity Impairment - Specific Health Problem (WPAI-SHP) Questionnaire at Week 52 LOCF.
timeFrame: Up to 52 Weeks
measure: Proportion of subjects satisfied with their treatment at Week 52 LOCF.
timeFrame: Up to 52 Weeks
Other outcomes:
Locations:
city: Alabaster
country: United States
facility: GSK Investigational Site
state: Alabama
city: Jasper
country: United States
facility: GSK Investigational Site
state: Alabama
city: Mesa
country: United States
facility: GSK Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Sun City
country: United States
facility: GSK Investigational Site
state: Arizona
city: Laguna Hills
country: United States
facility: GSK Investigational Site
state: California
city: Northridge
country: United States
facility: GSK Investigational Site
state: California
city: Oxnard
country: United States
facility: GSK Investigational Site
state: California
city: Pasadena
country: United States
facility: GSK Investigational Site
state: California
city: Redondo Beach
country: United States
facility: GSK Investigational Site
state: California
city: Reseda
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: Santa Monica
country: United States
facility: GSK Investigational Site
state: California
city: Colorado Springs
country: United States
facility: GSK Investigational Site
state: Colorado
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: Wheat Ridge
country: United States
facility: GSK Investigational Site
state: Colorado
city: Boca Raton
country: United States
facility: GSK Investigational Site
state: Florida
city: Largo
country: United States
facility: GSK Investigational Site
state: Florida
city: St. Petersburg
country: United States
facility: GSK Investigational Site
state: Florida
city: Stuart
country: United States
facility: GSK Investigational Site
state: Florida
city: Tampa
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Austell
country: United States
facility: GSK Investigational Site
state: Georgia
city: Dawsonville
country: United States
facility: GSK Investigational Site
state: Georgia
city: Macon
country: United States
facility: GSK Investigational Site
state: Georgia
city: Woodstock
country: United States
facility: GSK Investigational Site
state: Georgia
city: Oak Brook
country: United States
facility: GSK Investigational Site
state: Illinois
city: Lenexa
country: United States
facility: GSK Investigational Site
state: Kansas
city: Topeka
country: United States
facility: GSK Investigational Site
state: Kansas
city: Baton Rouge
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Springfield
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Bingham Farms
country: United States
facility: GSK Investigational Site
state: Michigan
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Cherry Hill
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Toms River
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Endwell
country: United States
facility: GSK Investigational Site
state: New York
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Schenectady
country: United States
facility: GSK Investigational Site
state: New York
city: Greenville
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Medford
country: United States
facility: GSK Investigational Site
state: Oregon
city: Portland
country: United States
facility: GSK Investigational Site
state: Oregon
city: Columbia
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Mount Pleasant
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Jackson
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
city: Alexandria
country: United States
facility: GSK Investigational Site
state: Virginia
city: Charlottesville
country: United States
facility: GSK Investigational Site
state: Virginia
city: Spokane
country: United States
facility: GSK Investigational Site
state: Washington
city: Tacoma
country: United States
facility: GSK Investigational Site
state: Washington
city: Walla Walla
country: United States
facility: GSK Investigational Site
state: Washington
city: Wenatchee
country: United States
facility: GSK Investigational Site
state: Washington
city: Coquitlam
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Langley
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Ajax
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Regina
country: Canada
facility: GSK Investigational Site
state: Saskatchewan
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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).