Effects of Neupro on Cardiovascular Observations in Patients With Restless Legs Syndrome

Inclusion Criteria

• Subject is informed and given ample time and opportunity to think about her/his participation and give her/his written informed consent
• Subject understands the investigational nature of the study and is willing and able to comply with the study requirements. Subject is willing to accept that he/she might be treated with placebo during the Treatment Period
• Subject is able to apply/remove the study patch correctly
• Subject is male or female, and is ≥18 and ≤75 years of age
• Subject meets the diagnosis of idiopathic Restless Legs Syndrome (RLS) based on the 4 essential clinical features according to the International Restless Legs Syndrome Study Group (Allen et al,2003): 1. An urge to move legs, usually accompanied or caused by uncomfortable and unpleasant sensations in the legs (The urge to move can be present without uncomfortable sensations. Arms or other body parts can also be affected) 2. The urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity, such as lying or sitting 3. The urge to move or unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues 4. The urge to move or unpleasant sensations are worse in the evening or night than during the day or only occur in the evening or night (When symptoms are very severe, the worsening at night may not be noticeable but must have been previously present)
• Subject has a score of ≥11 on the RLS-Diagnostic Index (RLS-DI) (Benes and Kohnen, 2009)
• Subject has an initial response to previous dopaminergic treatment for RLS or has no previous dopaminergic treatment (ie, de novo)
• The subject's Body Mass Index (BMI) is ≥18 kg/m^2 and ≤35 kg/m^2
• At Baseline subject has a score of ≥15 on the IRLS (indicating moderate to severe RLS)
• At Baseline subject has a score of ≥4 points on the CGI Item 1 assessment (indicating moderately ill)
• At Baseline subject has a score of ≥15 PLM/h on the Periodic Limb Movements Index (PLMI) based on polysomnography (PSG) (recorded during the second night) as assessed by the investigator
• Subjects are on a concomitant dose of antihypertensives that is at a stable dose for at least 4 weeks prior to Baseline and hypertension is reasonably controlled while the subject agrees to continue at this dose for the duration of the study, or subject has not received concomitant treatment with antihypertensives for at least 4 weeks prior to Baseline and does not intend to start such use during the study

Exclusion Criteria

• Subject has RLS due to renal insufficiency (uremia), iron deficiency anemia, or rheumatoid arthritis
• Subject has RLS associated with previous or concomitant therapy with dopamine D2 receptor antagonists, butyrophenones, metoclopramide, atypical antipsychotics (eg, olanzapine), tri- and tetra-cyclic antidepressants, mianserine, or lithium or H2-blockers (eg, cimetidine), or due to withdrawal from drugs such as anticonvulsants, benzodiazepines, barbiturates, and other hypnotics
• Subject has a history of sleep disturbances, such as sleep apnea syndrome (including obstructive sleep apnea), narcolepsy, sleep attacks/sudden onset of sleep, or myoclonus epilepsy either observed during PSG (local PSG evaluations) or evidenced by subject history
• Subject has uncontrolled hypertension according to the judgment of the investigator
• Subject has additional clinically relevant concomitant diseases, such as attention deficit hyperactivity disorder, polyneuropathy, akathisia, claudication, varicosis, muscle fasciculation, painful legs and moving toes, or radiculopathy
• Subject has other central nervous system diseases, such as Parkinson's disease, dementia, progressive supranuclear paresis, multisystem atrophy, Huntington's chorea, amyotrophic lateral sclerosis, or Alzheimer's disease.
• Subject has a prior history of psychotic episodes
• Subject has a history of chronic alcohol or drug abuse within the p