Long-Term Study Of Ropinirole In Restless Legs Syndrome

Condition(s) targeted: Restless Legs Syndrome

Intervention: Ropinirole oral tablets (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trial, MD, Study Director, Affiliation: GlaxoSmithKline

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.

Official title: 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.

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Evaluation of efficacy of ropinirole in moderate to severe Restless Legs Syndrome at Weeks 12 and 26 using the International Restless Legs Syndrome Rating Scale. Frequency of clinically meaningful augmentation and early morning rebound of symptoms.

Secondary outcome:

Evaluation of efficacy of ropinirole over 66 weeks of treatment. Incidence of confirmed cases of augmentation (worsening of symptoms).

Double-blind phase Proportion of subjects with a score of much improved (2) or very much improved (1) on the Clinical Global Impression - Global Improvement (CGI-I) scale at Weeks 1, 12, and 26.

Change from baseline in the domains of the 12-item Medical Outcomes Study (MOS-12) Sleep Scale at Weeks 12 and 26.

Change from baseline in the IRLS Rating Scale total score at Weeks 1, 4, 8, 16, and 20.

Proportion of subjects withdrawing due to lack of efficacy during the first 26 weeks.

Time to first response during the double-blind phase, where response is defined as a score of much improved (2) or very much improved (1) on the CGI-I scale.

Clinical Global Impression - Severity of Illness (CGI-S) scale at Week 26.

Change from baseline in the Johns Hopkins RLS Quality of Life (RLS QoL) Questionnaire overall life impact score at 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.

Open-label phase Proportion of subjects with a score of much improved (2) or very much improved (1) on the CGI-I scale at Weeks 28, 31, 35, 39, 47, 55, 63, and 67.

Change from baseline in the IRLS Rating Scale total score at Weeks 28, 31, 35, 39, 47, 55, 63, and 67.

Minimum age: 18 Years. Maximum age: 79 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Male and female subjects, = 18 years and < 80 years of age.

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 as defined in Appendix 3.

- 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 (Appendix 4).

- 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)

(see Appendix 5).

- 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.

GSK Clinical Trials Call Center, Melbourne East, Australia; Recruiting
GSK Clinical Trials Call Center, Phone: 1-877-379-3718

GSK Clinical Trials Call Center, Camperdown 2050, Australia; Not yet recruiting
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GSK Clinical Trials Call Center, Clayton 3168, Australia; Not yet recruiting
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GSK Clinical Trials Call Center, Pardubice 53503, Czech Republic; Recruiting
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GSK Clinical Trials Call Center, Olomouc 77520, Czech Republic; Not yet recruiting
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GSK Clinical Trials Call Center, Praha 12000, Czech Republic; Not yet recruiting
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GSK Clinical Trials Call Center, Ostrava 70200, Czech Republic; Recruiting
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GSK Clinical Trials Call Center, Aalborg 9000, Denmark; Recruiting
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GSK Clinical Trials Call Center, Vejle 7100, Denmark; Recruiting
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GSK Clinical Trials Call Center, Paris Cedex 13 75651, France; Not yet recruiting
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GSK Clinical Trials Call Center, Grenoble Cedex 09 38043, France; Not yet recruiting
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GSK Clinical Trials Call Center, Bron 69677, France; Not yet recruiting
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GSK Clinical Trials Call Center, Paris Cedex 04 75181, France; Not yet recruiting
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GSK Clinical Trials Call Center, Regensburg 93053, Germany; Recruiting
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GSK Clinical Trials Call Center, Quickborn 25451, Germany; Not yet recruiting
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GSK Clinical Trials Call Center, Marburg 35039, Germany; Not yet recruiting
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GSK Clinical Trials Call Center, Schwerin 19053, Germany; Not yet recruiting
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GSK Clinical Trials Call Center, Bamberg 96047, Germany; Recruiting
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GSK Clinical Trials Call Center, Berlin 10969, Germany; Recruiting
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GSK Clinical Trials Call Center, Budapest 1126, Hungary; Not yet recruiting
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GSK Clinical Trials Call Center, Bologna 40123, Italy; Recruiting
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GSK Clinical Trials Call Center, Roma 163, Italy; Recruiting
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GSK Clinical Trials Call Center, Pavia 27100, Italy; Not yet recruiting
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GSK Clinical Trials Call Center, Roma 168, Italy; Not yet recruiting
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GSK Clinical Trials Call Center, Hamar N-2317, Norway; Recruiting
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GSK Clinical Trials Call Center, Coimbra 3000-075, Portugal; Recruiting
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GSK Clinical Trials Call Center, Lisboa 1649-035, Portugal; Not yet recruiting
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GSK Clinical Trials Call Center, Bratislava 83305, Slovakia; Not yet recruiting
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GSK Clinical Trials Call Center, Levice 05401, Slovakia; Not yet recruiting
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GSK Clinical Trials Call Center, Bratislava 83103, Slovakia; Not yet recruiting
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GSK Clinical Trials Call Center, Zilina 01207, Slovakia; Not yet recruiting
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GSK Clinical Trials Call Center, San Sebastian 20014, Spain; Recruiting
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GSK Clinical Trials Call Center, Barcelona 08017, Spain; Not yet recruiting
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GSK Clinical Trials Call Center, Madrid 28036, Spain; Not yet recruiting
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GSK Clinical Trials Call Center, ALVESTA SE-77482, Sweden; Recruiting
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GSK Clinical Trials Call Center, Orebro 70185, Sweden; Recruiting
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GSK Clinical Trials Call Center, Goteborg SE-412 55, Sweden; Recruiting
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GSK Clinical Trials Call Center, Bern 3010, Switzerland; Not yet recruiting
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GSK Clinical Trials Call Center, Zurich 5330, Switzerland; Not yet recruiting
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GSK Clinical Trials Call Center, Zurich 8091, Switzerland; Not yet recruiting
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GSK Clinical Trials Call Center, Luzern 6006, Switzerland; Not yet recruiting
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Starting date: March 2006
Ending date: September 2008
Last updated: March 4, 2008