The objective of this study is to evaluate the effects of stimulation of dopaminergic D2, D3 receptors on spinal cord excitability and on the severity of symptoms in patients with mild to moderately advanced restless legs syndrome. In a controlled proof-of-principle clinical study, the acute efficacy of ropinirole will be assessed through the use of validated electrophysiological tests and severity scales. Safety will be monitored by means of frequent clinical evaluations and laboratory tests.
- INCLUSION CRITERIA: Subjects who meet all of the following inclusion criteria at screening or Day 0 will be eligible to participate in the study: 1. Male or female subjects aged 18 to 80. 2. Body Mass Index within the range 19-34 kg/m(2) inclusive. 3. For patients only, diagnosed with mild to moderate RLS based on the presence of a characteristic clinical history and the IRLSSG diagnostic criteria. 4. Normal physical and neurological examination. 5. Subject is willing to adhere to protocol requirements as evidenced by written, informed consent. 6. No clinical significant abnormalities on clinical chemistry or haematology examination at the pre-study medical evaluation. 7. A normal 12 lead ECG at the pre-study medical. 8. A negative pre-study Hepatitis B surface antigen and Hepatitis C antibody result within 3 months of the start of the study. 9. Negative pre-study urine drug screen. 10. RLS Rating Scale score of greater than or equal to 15 at the time of baseline evaluation, after medication wash out. 11. Presence of PLMs by convincing history, or document by SIT or polysomnography tests at the time of baseline evaluation. EXCLUSION CRITERIA: Subjects meeting any of the following exclusion criteria either at Day 0 or during the study will not be enrolled or will be immediately excluded from the study, as appropriate: 1. History of any medical condition that can reasonably be expected to subject the individual to unwarranted risk or compromise scientific integrity of the study; 2. History or presence of gastro-intestinal, hepatic or renal disease or other condition known to interfere with the absorption, distribution, metabolism or excretion drugs 3. Clinically significant laboratory abnormalities including liver enzyme elevation greater than twice the upper limit of normal; 4. Patient unwilling or unable to stop their usual medications for RLS; 5. Subjects unable or unwilling to discontinue a prohibited concomitant medication; 6. Subjects who have received prescribed medication within 7 days prior to the first dosing day (defined as Day 1), which in the opinion of the Principal Investigator will interfere with the study procedures or compromise safety. 7. Withdrawal, introduction, or change in dose of hormone replacement therapy (HRT) and/or any drug known to substantially inhibit or induce CYP1A2 within 2 weeks prior to first dose (Day 1). 8. Patients suffering from RLS symptoms during the daytime (daytime defined as 10.00 until 16.00 hours). 9. Subjects who have not been using a clinically accepted contraceptive method (such as oral contraception, surgical sterilization, IUD, diaphragm in conjunction with spermicidal foam and condom on the male partner, or systemic contraception) for the last 30 days, or is not at least one year post-menopausal (if female); 10. Subjects who are pregnant or breastfeeding; 11. Subjects with cognitive impairment (MMSE less than 25); 12. Subjects who have participated in a clinical study with an investigational drug within the last 3 months; 13. Subjects with history or presence of active drug or alcohol abuse that, in the opinion of the investigators, would interfere with compliance or safety or scientific integrity of study; 14. Subjects unwilling to sign an informed consent or to comply with protocol requirements. 15. A dissomnia or parasomnia other than, in patients, primary RLS (e.g. narcolepsy, sleep tenor disorder, sleepwalking disorder, and breathing-related sleep disorder), either from clinical review or from polysomnography (including subjects with apnea hypopnea index greather than 5/h). 16. Signs of secondary RLS (e.g. renal failure (end-stage renal disease), iron deficient anemia or pregnancy at baseline). 17. Subjects with clinical and/or biochemical evidence of iron deficiency. 18. Subjects with a diastolic blood pressure greater than or equal to 110mmHg or less than or equal to 50mmHg OR systolic blood pressure greater than or equal 180mmHg or less than or equal 90mmHg at baseline. 19. Subjects with known intolerance to ropinirole or other dopaminergic agonist. 20. Patients with symptomatic orthostatic hypotension.