A Parallel Group Study to Evaluate the Efficacy and Safety of Ropinirole for 26 Weeks and to Further Evaluate the Incidence of Augmentation and Rebound for a Further 40 Weeks Open-label Extension Treatment Period in Subjects Suffering From Moderate to Severe Restless Legs Syndrome.
Overview
- Phase
- Phase 4
- Intervention
- Placebo
- Conditions
- Restless Legs Syndrome
- Sponsor
- GlaxoSmithKline
- Enrollment
- 404
- Locations
- 1
- Primary Endpoint
- Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
This is an initial placebo-controlled study followed by open treatment evaluating the effectiveness and tolerability of ropinirole long-term in patients with moderate to severe Restless Legs Syndrome.
Detailed Description
A randomised, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of ropinirole for 26 weeks and to further evaluate the incidence of augmentation and rebound for a further 40 weeks open-label extension treatment period in subjects suffering from moderate to severe Restless Legs Syndrome.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male and female subjects, between the ages of 18 and 79, inclusive
- •A female is eligible to enter and participate in the study if she is of:
- •Non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or,
- •Childbearing potential, has a negative result on all required pregnancy tests prior to randomisation, and agrees to an acceptable contraceptive method.
- •Subjects with a diagnosis of idiopathic RLS using the RLS Diagnostic Clinical Interview and the International RLS Study Group (IRLSSG) Diagnostic Criteria during the Screening Visit.
- •Subjects have had RLS symptoms with a history of a minimum of 15 RLS episodes during the previous month. If this is not possible due to the subject being on previous medication to treat RLS the investigator should ensure that the subject should have experienced 4-5 episodes of RLS symptoms during the last 7 days of the wash-out phase (see below). The subject must discontinue and wash-out any previous medication for the treatment of RLS or sleep prior to the Baseline Visit (Day 0). The minimum discontinuation period for wash-out is generally 5 half-lives of the medication or 7 consecutive evenings/nights medication-free prior to baseline, whichever is the longer period.
- •During the Wash-out and Screening Phase, RLS symptoms must be present for at least 4 of the last 7 nights immediately prior to the Baseline Visit (e.g., any combination of evenings and /or nights for = 4 days).
- •Subjects with a total score = 24 on the IRLS Rating Scale at baseline (Day 0).
- •Subjects with RLS symptoms that cause significant sleep impairment based on clinical judgment and guided by subject response to Question 4 of the IRLS Rating Scale (e.g., ordinarily this will include a response of (3) severe or (4) very severe sleep disturbance) at the Baseline Visit OR RLS symptoms that cause severe/very severe discomfort in the limbs based on clinical judgment and guided by subject response to Question 1 of the IRLS Rating Scale (e.g., this will include a response of (3) severe or (4) very severe discomfort in limbs) at the Baseline Visit (Day 0).
- •Subjects must be experiencing RLS symptoms requiring treatment at night-time.
Exclusion Criteria
- Not provided
Arms & Interventions
Double-blind for 12 to 26 Weeks
Double-blind (Ropinirole:Placebo) for 12 to 26 weeks
Intervention: Placebo
Double-blind for 12 to 26 Weeks
Double-blind (Ropinirole:Placebo) for 12 to 26 weeks
Intervention: Ropinirole
Open-label ropinirole for 40-Weeks
Open label ropinirole for 40 weeks
Intervention: Ropinirole
Outcomes
Primary Outcomes
Number of Participants With Clinically Meaningful Augmentation and Early Morning Rebound (EMR) Cases
Time Frame: During 15-month study duration at scheduled (Weeks 16, 20, 26, or early withdrawal for DB phase; Weeks 39, 47, 55, 63, 67, or early withdrawal for the OL phase) and unscheduled (26-week DB phase and 40-week OL phase) visits
Clinically meaningful augmentation and early morning rebound (EMR) were assessed and confirmed by an independent Adjudication Board. EMR describes the development of RLS symptoms during the early morning, following therapeutic intervention. EMR is differentiated from augmentation, in which the earlier onset of symptoms occurs in the evening.
Mean Change From Baseline in the International Restless Legs Syndrome (IRLS) Rating Scale Total Score at Week 12 and Week 26
Time Frame: Baseline and Weeks 12 and 26
A 10-item, participant-reported scale covering different symptoms of the condition. Each item is scored from 0 to 4; 0 represents the absence of a problem and 4 reflects a very severe problem. The best and worst possible scores are 0 and 40, respectively; higher scores represent a greater severity of symptoms. A negative change from baseline indicates improvement, and a negative treatment difference indicates a benefit of Ropinirole IR over placebo. The primary assessment was made by calculating the difference in the average score obtained at Baseline with scores at Week 12 and then Week 26.
Secondary Outcomes
- Mean Change From Baseline in the International RLS (IRLS) Rating Scale Total Score at Weeks 1, 4, 8, 16, and 20(Baseline and Weeks 1, 4, 8, 16, and 20)
- Change From Baseline in the Domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26(Baseline and Weeks 12 and 26)
- Median Time to First CGI-I Response of Much/Very Much Improved During the Double-blind Phase(Baseline to Week 26)
- Percentage of Participants With a Score of Much/Very Much Improved on the Clinical Global Impression-Global Improvement (CGI-I) Scale at Weeks 1, 12 and 26(Weeks 1, 12 and 26)
- Mean Change From Baseline in the IRLS Rating Scale Total Score at Week 67(Baseline and Week 67)
- Change From Baseline in Sleep Quantity, a Domain of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale, at Weeks 12 and 26(Baseline and Weeks 12 and 26)
- Change From Baseline in the Johns Hopkins RLS Quality of Life (RLS QoL) Questionnaire Overall Life Impact Score at Weeks 12 and 26(Baseline and Weeks 12 and 26)
- Change From Baseline in the Domains of the MOS 36-item Short Form Health Survey (SF-36) at Weeks 12 and 26(Baseline and Weeks 12 and 26)
- Number of Participants Withdrawing Due to Lack of Efficacy During the First 26 Weeks of the Study(Baseline to Week 26)
- Number of Participants Rated as Normal or Borderline Ill on the CGI Severity of Illness (CGI-S) Scale at Week 26(Week 26)
- Number of Participants With a Score of Much/Very Much Improved on the CGI-I Scale at Week 67(Week 67)