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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB, Inc. ( UCB BIOSCIENCES GmbH )
ClinicalTrials.gov Identifier:
NCT01537042
First received: February 16, 2012
Last updated: October 30, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Restless Legs Syndrome
End-Stage Renal Disease
Drug: Rotigotine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by UCB, Inc.:

Primary Outcome Measures:
  • Ratio from Baseline to the end of the 2-week Maintenance Period in Periodic Limb Movement Index (PLMI) [ Time Frame: From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period ] [ Designated as safety issue: No ]

    The PLMI is defined as Periodic Limb Movements (PLMs)/ total time in bed in hours. PLMs are measured by Polysomnography (PSG).

    The reduction of the PLMI is reflected in terms of the ratio from Baseline to the end of the Maintenance Period.



Secondary Outcome Measures:
  • Change from Baseline in the Periodic Limb Movements Index (PLMI) to the end of the Maintenance Period [ Time Frame: From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period ] [ Designated as safety issue: No ]
    The PLMI is defined as Periodic Limb Movements (PLMs)/ total time in bed in hours. PLMs are measured by Polysomnography (PSG).

  • Change from Baseline in the International Restless Legs Syndrome Study Group Rating Scale (IRLS) sum score to the end of the Maintenance Period [ Time Frame: From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period ] [ Designated as safety issue: No ]

    The IRLS is a subject based scale that consists of 10 items to evaluate the severity of major RLS symptoms and the impact of the disease on subjects' functioning in daytime activities. Each of the 10 items is measured on a scale that ranges from 0 (not present) to 4 (severe).

    A sum score between 0 (no RLS symptoms present at all) and 40 (maximum severity in all symptoms) across all 10 items will be calculated.


  • Change from Baseline in Clinical Global Impressions (CGI) Item 1 score to the end of the Maintenance Period [ Time Frame: From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period ] [ Designated as safety issue: No ]
    The CGI Item 1 score measures the severity of illness on a scale that ranges from 1 (not at all ill) to 7 (extremely severe ill).

  • Change from Baseline in the Restless Legs-6 (RLS-6) Rating Scale 1 to the end of the Maintenance Period [ Time Frame: From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period ] [ Designated as safety issue: No ]

    The RLS-6 exists of six scales of which four scales are designed to assess severity of RLS and two scales cover sleep and daytime tiredness.

    Scale 1 measures the severity of RLS at time falling asleep on a 11-point scale that ranges between 0 (not at all) to 10 (maximum). The ratings are given by the subjects.


  • Change from Baseline in the Restless Legs-6 (RLS-6) Rating Scale 2 to the end of the Maintenance Period [ Time Frame: From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period ] [ Designated as safety issue: No ]

    The RLS-6 exists of six scales of which four scales are designed to assess severity of RLS and two scales cover sleep and daytime tiredness.

    Scale 2 measures the severity of RLS during the night on a 11-point scale that ranges between 0 (not at all) to 10 (maximum). The ratings are given by the subjects.


  • Change from Baseline in the Restless Legs-6 (RLS-6) Rating Scale 3 to the end of the Maintenance Period [ Time Frame: From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period ] [ Designated as safety issue: No ]

    The RLS-6 exists of six scales of which four scales are designed to assess severity of RLS and two scales cover sleep and daytime tiredness.

    Scale 3 measures the severity of RLS during the day at rest on a 11-point scale that ranges between 0 (not at all) to 10 (maximum). The ratings are given by the subjects.


  • Change from Baseline in the Restless Legs-6 (RLS-6) Rating Scale 4 to the end of the Maintenance Period [ Time Frame: From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period ] [ Designated as safety issue: No ]

    The RLS-6 exists of six scales of which four scales are designed to assess severity of RLS and two scales cover sleep and daytime tiredness.

    Scale 4 measures the severity of RLS during the day when engaged in daytime activities on a 11-point scale that ranges between 0 (not at all) to 10 (maximum). The ratings are given by the subjects.


  • Change from Baseline in the Restless Legs-6 (RLS-6) Rating Scale 5 to the end of the Maintenance Period [ Time Frame: From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period ] [ Designated as safety issue: No ]

    The RLS-6 exists of six scales of which four scales are designed to assess severity of RLS and two scales cover sleep and daytime tiredness.

    Scale 5 measures the satisfaction with sleep on a 11-point scale that ranges between 0 (not at all) to 10 (maximum). The ratings are given by the subjects.


  • Change from Baseline in the Restless Legs-6 (RLS-6) Rating Scale 6 to the end of the Maintenance Period [ Time Frame: From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period ] [ Designated as safety issue: No ]

    The RLS-6 exists of six scales of which four scales are designed to assess severity of RLS and two scales cover sleep and daytime tiredness.

    Scale 6 measures the severity of daytime tiredness/sleepiness on a 11-point scale that ranges between 0 (not at all) to 10 (maximum). The ratings are given by the subjects.


  • Change from Baseline in the Periodic Limb Movement during Sleep Arousal Index (PLMSAI) to the end of the Maintenance Period [ Time Frame: From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period ] [ Designated as safety issue: No ]
    The Periodic Limb Movement during Sleep Arousal Index (PLMSAI) reflects the influence of the PLM on subject's sleep. Arousal is defined as sudden change in the Electroencephalogram (EEG) activity and the index illustrates to what degree the PLMs contribute to arousal from sleep.

  • Change from Baseline in sleep efficiency to the end of the Maintenance Period [ Time Frame: From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period ] [ Designated as safety issue: No ]
    Sleep stages and time spent in each sleep stage are determined from Electroencephalogram (EEG) readings. Sleep stage data will be used to calculate sleep efficiency. Sleep efficiency will be presented as percentages.

  • Change from Baseline in the Restless Legs-Quality of Life (RLS-QoL) total score to the end of the Maintenance Period [ Time Frame: From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period ] [ Designated as safety issue: No ]
    The RLS-QoL is a disease-specific questionnaire to evaluate quality of life. It consists of 12 items. A total score will be calculated from all of the 12 items.

  • Change from Baseline in the Short-Form-36 (SF-36) item questionnaire Mental Component Summary (MCS) to the end of the Maintenance Period [ Time Frame: From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period ] [ Designated as safety issue: No ]
    The SF-36 measures the Health Related Quality of Life (HRQoL). It is a 36-item survey that measures eight domains of health. Four of these domains belong to physical health and four domains to mental health. Domain scores are generated from the SF-36. In addition, two summary scores can also be derived from the SF-36: The Physical Component Summary (PCS) and the Mental Component Summary (MCS).

  • Change from Baseline in the Short-Form-36 (SF-36) item questionnaire Physical Component Summary (PCS) to the end of the Maintenance Period [ Time Frame: From Baseline over the Up-Titration Period (up to 3 Weeks) to the end of the 2-Week Maintenance Period ] [ Designated as safety issue: No ]
    The SF-36 measures the Health Related Quality of Life (HRQoL). It is a 36-item survey that measures eight domains of health. Four of these domains belong to physical health and four domains to mental health. Domain scores are generated from the SF-36. In addition, two summary scores can also be derived from the SF-36: The Physical Component Summary (PCS) and the Mental Component Summary (MCS).


Enrollment: 30
Study Start Date: April 2012
Study Completion Date: October 2013
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rotigotine

Rotigotine Transdermal Patch

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.

Drug: Rotigotine

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.

Other Name: Neupro
Placebo Comparator: Placebo
Transdermal patch matched according to patch size and appearance.
Drug: Placebo

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.


  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01537042

Locations
United States, Florida
606
Brandon, Florida, United States
United States, Massachusetts
604
Newton, Massachusetts, United States
United States, New York
603
West Seneca, New York, United States
United States, Ohio
607
Dublin, Ohio, United States
United States, Pennsylvania
605
West Chester, Pennsylvania, United States
United States, Texas
601
Austin, Texas, United States
Austria
101
Innsbruck, Austria
Finland
201
Helsinki, Finland
203
Tampere, Finland
France
302
Bordeaux Cedex, France
301
Montpellier Cédex 5, France
Germany
404
Berlin, Germany
401
Marburg, Germany
402
Schwerin, Germany
Italy
502
Pisa, Italy
Sponsors and Collaborators
UCB BIOSCIENCES GmbH
Investigators
Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)
  More Information

No publications provided

Responsible Party: UCB, Inc. ( UCB BIOSCIENCES GmbH )
ClinicalTrials.gov Identifier: NCT01537042     History of Changes
Other Study ID Numbers: SP0934, 2011-003486-15
Study First Received: February 16, 2012
Last Updated: October 30, 2013
Health Authority: Austria: Agency for Health and Food Safety
Finland: Finnish Medicines Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
United States: Food and Drug Administration

Keywords provided by UCB, Inc.:
Rotigotine
Neupro
Restless Legs Syndrome
RLS
End-Stage Renal Disease

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Restless Legs Syndrome
Psychomotor Agitation
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Nervous System Diseases
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Parasomnias
Mental Disorders
Dyskinesias
Neurologic Manifestations
Psychomotor Disorders
Neurobehavioral Manifestations
Signs and Symptoms
N 0437
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014