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
Condition: Restless Legs Syndrome; End-Stage Renal Disease
MeSH terms: Psychomotor Agitation; Restless Legs Syndrome; Kidney Diseases; Kidney Failure, Chronic; Syndrome
Intervention: Rotigotine; Placebo
Intervention description: Transdermal patch; Dose: 1 mg/24 h, 2 mg/24 h or 3 mg/24 h once daily depending on optimal dose; maximal dose is 3 mg/24 h.
Subjects start with a Rotigotine dose of 1 mg/24 h for 1 week. The dose can be increased weekly during Up-Titration Period until either the optimal or the maximal dose of 3 mg/24 h has been reached. Subjects will maintain the optimal/maximal dose during the 2-week Maintenance Period. Following the Maintenance Period, subjects will be de-escalated from their optimal dose by decreasing the dose by 1 mg/24 h every other day during Taper Period until complete withdrawal.; Transdermal patch; Patches matching to active treatment patches in size and appearance.
Up to 3 weeks of Titration,
2 weeks of Maintenance,
Up to 4 days of Taper Period.
Intervention MeSH terms: Rotigotine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Rotigotine; Neupro; Restless Legs Syndrome; RLS; End-Stage Renal Disease

Summary:

      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.
    

Eligibility criteria:

        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