Long-term Study Of Ropinirole In Restless Legs Syndrome
Condition: Restless Legs Syndrome
MeSH terms: Psychomotor Agitation; Restless Legs Syndrome; Syndrome
Intervention: Placebo; Ropinirole
Intervention description: Matching Placebo; Ropinirole IR 0.25mg/day to 4mg/day for RLS
Intervention MeSH terms: Ropinirole
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 404.0
Sex: All
Minimum age: 18 Years
Maximum age: 79 Years
Healthy volunteers: No
Keywords: Moderate; Restless Legs Syndrome; Severe; ropinirole

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.
    

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:

          1. Non-childbearing potential (i.e., physiologically incapable of becoming pregnant,
             including any female who is post-menopausal); or,

          2. 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.

               -  Subjects must have given written informed consent prior to any specific study
                  procedures.

        Exclusion criteria:

          -  Subjects suffering from augmentation and/ or 'end of treatment' rebound RLS symptoms
             at baseline (Day 0). Augmentation is defined as RLS symptoms that occurred while on
             treatment and occur earlier in the afternoon/evening 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 treatment' rebound describes worsening of
             symptoms from baseline that occur after pharmacological treatment is stopped.

          -  Subjects with a previous history of augmentation.

          -  Subjects who have exhibited intolerance to ropinirole or any other dopamine agonist.

          -  Subjects requiring treatment of daytime RLS symptoms (daytime defined as 10:00 hours
             until 17:00 hours).

          -  Signs of secondary RLS (e.g., end stage renal disease, iron deficient anaemia or
             pregnancy at Baseline Visit).

          -  Subjects with a serum ferritin level of < 10 mcg/L (ng/mL) at Screening Visit.

          -  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).

          -  Subjects who have medical conditions which 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, major psychotic illness.

          -  Subjects having a clinically significant abnormal laboratory value, ECG, or physical
             examination findings not resolved by the time of the baseline examinations (Day 0).
             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 alcohol or substance abuse within the past year.

          -  Subjects taking any medication known to induce drowsiness, affect RLS or sleep and
             which have not been discontinued prior to the Baseline Visit. These medications
             include the following:

        Atypical and typical antipsychotics, anticonvulsants, opioids (including propoxyphene and
        oxycodone), anxiolytics, all sedatives/hypnotics (including benzodiazepines), lithium, oral
        neuroleptics, stimulants (including methylphenidate), dopamine agonists (including
        ropinirole), dopamine antagonists (e.g., typical neuroleptics, metoclopramide),
        levodopa/carbidopa, clonidine, and sedating antihistamines (e.g., chlorpheniramine,
        diphenhydramine, hydroxyzine) or any preparations containing these antihistamines.

        The minimum discontinuation period is generally 5 half lives or 7 consecutive
        evenings/nights medication free, prior to baseline, whichever is the longer period.
        Exceptions to this general rule are: fluoxetine, monoamine oxidase inhibitors: 4 weeks.

        For subjects entering the 40-week, open-label treatment phase, the GSK Medical Monitor can
        be contacted to discuss individual cases where adherence to the above may not have
        occurred.

          -  Withdrawal, introduction, or change in dose of hormone replacement therapy (HRT)
             and/or any drug known to substantially inhibit CYP1A2 (e.g., ciprofloxacin,
             cimetidine, fluvoxamine, HRT) or induce CYP1A2 (e.g., tobacco, omeprazole) within 7
             days prior to enrolment. Subjects already on these agents may be enrolled, but must
             remain on stable doses of the agents from 7 days prior to enrolment through to the
             follow-up visit at the end 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.

          -  Participation in any clinical drug or device trial in the one month prior to the
             Baseline Visit.

          -  Subjects who, in the opinion of the investigator, would be non-compliant with the
             visit schedules or other study procedures.

          -  Women who have a positive pregnancy test or who are lactating.