A Sleep Laboratory Study to Investigate the Safety and Efficacy of the Rotigotine Skin Patch in Subjects With Restless Legs Syndrome and End-Stage Renal Disease Requiring Hemodialysis

A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel-group, Polysomnography Study to Investigate Safety and Efficacy of the Rotigotine Transdermal Patch in Subjects With Restless Legs Syndrome and End-Stage Renal Disease Requiring Hemodialysis

This is a sleep laboratory study to evaluate the efficacy and safety of Rotigotine in subjects with Restless Legs Syndrome and End-Stage Renal Disease requiring hemodialysis.

The objectives are to demonstrate superiority of Rotigotine against Placebo as well as to investigate the effect of Rotigotine on quality of life and sleep.

Inclusion Criteria:

• End-Stage Renal Disease (ESRD) requiring hemodialysis and regular dialysis schedule
• Fulfillment of pre-defined criteria of hematology parameters
• Diagnosis of Restless Legs (RLS) based on the 4 cardinal diagnostic clinical features according to the International Restless Legs Syndrome Study Group
• Initial response to previous dopaminergic treatment for RLS, or has had no previous dopaminergic treatment (ie, de novo)
• Score of ≥ 15 points on the IRLS (indicating moderate to severe RLS) at Baseline
• Score of ≥ 11 points on the RLS-DI (Diagnostic Index) at Baseline
• Score of ≥ 4 points on the Clinical Global Impressions (CGI) Item 1 assessment (indicating moderately ill) at Baseline
• Scores ≥ 15 Periodic Limb Movements (PLMs) per hour on the Periodic Limb Movement Index (PLMI) based on Polysomnography (PSG) (recorded during the second night) as assessed by the investigator at Baseline

Exclusion Criteria:

• Clinically relevant Polyneuropathy or Varicosis which cannot be clearly differentiated from RLS symptoms in the opinion of the investigator
• Clinically relevant concomitant diseases, such as Attention Deficit Hyperactivity Disorder, Painful Legs, and Moving Toes
• Other central nervous system diseases
• Evidence of an impulse control disorder according to the modified Minnesota Impulsive Disorders Interview (mMIDI)
• Lifetime history of suicide attempt (including an active attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response ('yes') to either Question 4 or Question 5 of the Columbia-Suicidality Severity Rating Scale (C-SSRS) at Screening (Visit 1) or Baseline (Visit 2)
• Prior history of psychotic episodes
• History of symptomatic (not asymptomatic) Orthostatic Hypotension
• Clinically relevant Cardiovascular Disease
• Clinically relevant Venous or Arterial Peripheral Vascular Disease
• Malignant Neoplastic Disease requiring therapy within 12 months prior to Screening (Visit 1)
• Treatment with any of the following drug classes: neuroleptics, norepinephrine and dopamine reuptake inhibitors (bupropion), gabapentin, budipine, dopamine antagonist antiemetics (except domperidone), opioids, monoamine oxidase (MAO) inhibitors, catechol-O-methyltransferase (COMT) inhibitors, or psychostimulants (eg, amphetamines)
• Subject is pregnant, nursing, or is a woman of childbearing potential who is not surgically sterile, 2 years postmenopausal, or does not consistently use 2 combined effective methods of contraception (including at least 1 barrier method), unless sexually abstinent
• Previous treatment with dopamine agonists within a period of 14 days prior to Baseline (Visit 2), or L-dopa within 7 days prior to Baseline (Visit 2)
• Medical history indicating intolerability to dopaminergic therapy (if pretreated) or has experienced Augmentation (Garcia-Borreguero and Williams, 2010) when previously treated with any dopaminergic agent
• Subject has received previous treatment with Rotigotine
• Known hypersensitivity to any of the components of the study medication, such as a history of significant Skin Hypersensitivity to adhesives, known Hypersensitivity to other transdermal medications, or unresolved Contact Dermatitis