Rotigotine Effect on All-day Functioning and Quality of Life in Subjects With Moderate to Severe Restless Legs Syndrome (RLS) (RESTORE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB, Inc.
ClinicalTrials.gov Identifier:
NCT01569464
First received: March 30, 2012
Last updated: June 13, 2013
Last verified: June 2013
  Purpose

The purpose of the study is to show that Rotigotine improves Restless Legs Syndrome (RLS) symptoms in subjects with moderate to severe RLS during both day and evening.


Condition Intervention Phase
Restless Legs Syndrome
Drug: Rotigotine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3B, Double-Blind, Randomized, Placebo-Controlled Study of Rotigotine and Its Effect on All-Day Functioning and Quality of Life in Subjects With Moderate to Severe Idiopathic Restless Legs Syndrome

Resource links provided by NLM:


Further study details as provided by UCB, Inc.:

Primary Outcome Measures:
  • Change From Baseline To The End Of The Maintenance Period in International Restless Legs Scale (IRLS) Sum Score [ Time Frame: Baseline to End of Maintenance Period (approximately 7 weeks) ] [ Designated as safety issue: No ]

    The International Restless Legs Scale (IRLS) is intended to evaluate, in a standardized way, the subjective intensity of major symptoms of Restless Legs Syndrome (RLS) and, in 2 items (9 and 10), the impact of the disease on subjects functioning in daytime activities by use of a 5-point scale for each of a total of 10 items.

    In all items, the scores range from 0 (not present) to 4 (severe). A sum score across all 10 items is calculated for analysis, which varies between 0 (no RLS symptoms present at all) to 40 (maximum severity in all symptoms).


  • Change In Average Of Means Of Multiple Suggested Immobilization Test Discomfort Scale (m-SIT-DS) Values Of Each Individual Suggested Immobilization Test (SIT) For The Combination Of Multiple Suggested Immobilization Test (m SIT) [ Time Frame: Baseline to End of Maintenance Period (approximately 7 weeks) ] [ Designated as safety issue: No ]

    The Multiple Suggested Immobilization Test Discomfort Scale (m-SIT-DS) will be used for assessment of the sensory components of Restless Legs Syndrome (RLS) symptoms in order to provide a subjective score of the severity of RLS symptoms during each Suggested Immobilization Test (SIT).

    Scores range from 0 (no symptoms) to 10 (very severe symptoms) and will be assessed every 10 minutes within each SIT.



Secondary Outcome Measures:
  • Change In Average Of Means Of Periodic Limb Movement During Wakefulness Index (PLMWI) Change In Average Of Means Of Periodic Limb Movement During Wakefulness Index (PLMWI) For The Combination Of Multiple Suggested Immobilization Test (m SIT) [ Time Frame: Baseline to End of Maintenance Period (approximately 7 weeks) ] [ Designated as safety issue: No ]

    During each single Suggested Immobilization Test (SIT) PLMWI will be measured using a validated actigraphy device. Simultaneous actigraphy of the legs will be performed by an actigraphy device, which will be attached to the ankle prior to the start of the SIT. The PLMWI will be recorded while the subject is awake.

    Scores range from 0 (no symptoms) to 10 (very severe symptoms) and will be assessed every 10 minutes within each SIT.


  • Change In Item Score From Baseline To The End Of The Maintenance Period In Satisfaction With Sleep (Item 1 of Restless Legs Syndrome 6 Rating Scale [RLS 6]) [ Time Frame: Baseline to End of Maintenance Period (approximately 7 weeks) ] [ Designated as safety issue: No ]
    The RLS 6 is an 11-point scale. This 11-point scale is provided with ranges between (0 = not at all) to (10 = maximum).

  • Change In Item Score From Baseline To The End Of The Maintenance Period In Severity Of Restless Legs Syndrome (RLS) At Bedtime (Item 2 of Restless Legs Syndrome 6 Rating Scale [RLS 6]) [ Time Frame: Baseline to End of Maintenance Period (approximately 7 weeks) ] [ Designated as safety issue: No ]
    The RLS 6 is an 11-point scale. This 11-point scale is provided with ranges between (0 = not at all) to (10 = maximum).

  • Change In Item Score From Baseline To The End Of The Maintenance Period In Severity Of Restless Legs Syndrome (RLS) During The Night (Item 3 of Restless Legs Syndrome 6 Rating Scale [RLS 6]) [ Time Frame: Baseline to End of Maintenance Period (approximately 7 weeks) ] [ Designated as safety issue: No ]
    The RLS 6 is an 11-point scale. This 11-point scale is provided with ranges between (0 = not at all) to (10 = maximum).

  • Change In Item Score From Baseline To The End Of The Maintenance Period In Severity Of Restless Legs Syndrome (RLS) At Daytime At Rest (Item 4 of Restless Legs Syndrome 6 Rating Scale [RLS 6]) [ Time Frame: Baseline to End of Maintenance Period (approximately 7 weeks) ] [ Designated as safety issue: No ]
    The RLS 6 is an 11-point scale. This 11-point scale is provided with ranges between (0 = not at all) to (10 = maximum).

  • Change In Item Score From Baseline To The End Of The Maintenance Period In Severity of Restless Legs Syndrome (RLS) At Daytime In Activity (Item 5 of Restless Legs Syndrome 6 Rating Scale [RLS 6]) [ Time Frame: Baseline to End of Maintenance Period (approximately 7 weeks) ] [ Designated as safety issue: No ]
    The RLS 6 is an 11-point scale. This 11-point scale is provided with ranges between (0 = not at all) to (10 = maximum).

  • Change In Item Score From Baseline To The End Of The Maintenance Period In Daytime Tiredness (Item 6 of Restless Legs Syndrome 6 Rating Scale [RLS 6]) [ Time Frame: Baseline to End of Maintenance Period (approximately 7 weeks) ] [ Designated as safety issue: No ]
    The RLS 6 is an 11-point scale. This 11-point scale is provided with ranges between (0 = not at all) to (10 = maximum).

  • Change From Baseline To The End Of Maintenance Period In Daytime Somnolence Domain Score Of The Medical Outcomes Study (MOS) Sleep Scale [ Time Frame: Baseline to End of Maintenance Period (approximately 7 weeks) ] [ Designated as safety issue: No ]
    The MOS Sleep Scale consists of 12 items. Subjects will answer each subscale in reference to the 4 weeks prior to their visit. If the timeframe since the last visit is less than 4 weeks, the subject will answer each subscale in reference to the days since their last visit. Subjects will self-report the length of time it took them to fall asleep and the average number of hours of sleep each night. Scores for all other items range from 1 (all of the time) to 6 (none of the time).

  • Change From Baseline To The End of Maintenance Period In Sleep Disturbance Domain Score Of The Medical Outcomes Study (MOS) Sleep Scale [ Time Frame: Baseline to End of Maintenance Period (approximately 7 weeks) ] [ Designated as safety issue: No ]
    The MOS Sleep Scale consists of 12 items. Subjects will answer each subscale in reference to the 4 weeks prior to their visit. If the timeframe since the last visit is less than 4 weeks, the subject will answer each subscale in reference to the days since their last visit. Subjects will self-report the length of time it took them to fall asleep and the average number of hours of sleep each night. Scores for all other items range from 1 (all of the time) to 6 (none of the time).

  • Change From Baseline To The End of Maintenance Period In Sleep Adequacy Domain Score Of The Medical Outcomes Study (MOS) Sleep Scale [ Time Frame: Baseline to End of Maintenance Period (approximately 7 weeks) ] [ Designated as safety issue: No ]
    The MOS Sleep Scale consists of 12 items. Subjects will answer each subscale in reference to the 4 weeks prior to their visit. If the timeframe since the last visit is less than 4 weeks, the subject will answer each subscale in reference to the days since their last visit. Subjects will self-report the length of time it took them to fall asleep and the average number of hours of sleep each night. Scores for all other items range from 1 (all of the time) to 6 (none of the time).

  • Change From Baseline To The End of Maintenance Period In Sleep Quantity Domain Score Of The Medical Outcomes Study (MOS) Sleep Scale [ Time Frame: Baseline to End of Maintenance Period (approximately 7 weeks) ] [ Designated as safety issue: No ]
    The MOS Sleep Scale consists of 12 items. Subjects will answer each subscale in reference to the 4 weeks prior to their visit. If the timeframe since the last visit is less than 4 weeks, the subject will answer each subscale in reference to the days since their last visit. Subjects will self-report the length of time it took them to fall asleep and the average number of hours of sleep each night. Scores for all other items range from 1 (all of the time) to 6 (none of the time).

  • Change In Total Score From Baseline To The End of Maintenance Period On Profile Of Mood States Questionnaire (POMS) [ Time Frame: Baseline to End of Maintenance Period (approximately 7 weeks) ] [ Designated as safety issue: No ]
    The POMS is a checklist of adjectives describing mood states. The subject rates the presence of each mood state in the past week on a 5-point scale from "not at all" to "extremely". The POMS is scored for 6 scales (fatigue, vigor, depression-dejection, anger-hostility, tension-anxiety, and confusion-bewilderment). In all scales but the vigor scale, higher scores reflect less mood disturbance; for the vigor scale, higher scores reflect less mood disturbance. The test is scored for each scale as well as for a total mood disturbance score derived from summing all scales.

  • Change from Baseline in SF-36 Mental Component Summary Score [ Time Frame: Baseline to End of Maintenance Period (approximately 7 weeks) ] [ Designated as safety issue: No ]
    The SF-36 is a 36-item general health-related Quality of Life (QOL) measure. It measures 8 general health concepts: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. These concepts are summarized as physical and mental components scores.

  • Change from Baseline in SF-36 Physical Component Summary Score [ Time Frame: Baseline to End of Maintenance Period (7 weeks) ] [ Designated as safety issue: No ]
    The SF-36 is a 36-item general health-related Quality of Life (QOL) measure. It measures 8 general health concepts: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. These concepts are summarized as physical and mental components scores.


Enrollment: 150
Study Start Date: March 2012
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Rotigotine
Rotigotine patches titrated from 1 mg/24 h - 3 mg/24 h or until effective or maximum dose is reached.
Drug: Rotigotine

Transdermal patch containing Rotigotine formulated in an adhesive matrix. Subjects will be treated with their optimal dose which consists of one of the dose strengths below:

Rotigotine 1 mg/24 h, Rotigotine 2 mg/24 h, Rotigotine 3 mg/24 h, One patch every 24 hours

7 weeks

Other Name: Neupro®
Placebo Comparator: Placebo
Placebo patches titrated from 1 mg/24 h - 3 mg/24 h or until effective or maximum dose is reached.
Drug: Rotigotine

Transdermal patch containing Rotigotine formulated in an adhesive matrix. Subjects will be treated with their optimal dose which consists of one of the dose strengths below:

Rotigotine 1 mg/24 h, Rotigotine 2 mg/24 h, Rotigotine 3 mg/24 h, One patch every 24 hours

7 weeks

Other Name: Neupro®

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • An Institutional Review Board (IRB)-approved written Informed Consent Form (ICF) is signed and dated by the subject
  • 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 male or female, and is ≥ 18 and ≤ 75 years of age
  • Subject is able to apply/remove the study patch correctly
  • Subject meets the diagnosis of Idiopathic Restless Legs Syndrome (IRLS) 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 the 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 down 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)
  • At Baseline (Visit 2), subject has a score of ≥ 11 on the RLS-Diagnostic Index (RLS-DI) (Benes and Kohnen, 2009)
  • Subject must attempt all 4 Suggested Immobilization Test (SIT) assessments at Baseline (Visit 2)
  • At Baseline (Visit 2) subject has an average Multiple Suggested Immobilization Test Discomfort Scale (m-SIT-DS) of at least 1.5 over the course of the Multiple Suggested Immobilization Test (m SIT)
  • The subject's Body Mass Index is ≥ 18 kg/m^2 and ≤ 35 kg/m^2 at Visit 1
  • At Baseline (Visit 2), subject has a score of ≥ 15 on the International Restless Legs Scale (IRLS) (indicating moderate to severe RLS)
  • At Baseline (Visit 2), subject has a score of "Severe" or "Very Severe" on Item 8 of the IRLS (Item 8: When you had RLS symptoms how severe were they on average?)
  • At Baseline (Visit 2), subject has a score of ≥ 4 points on the Clinical Global Impression (CGI) Item 1 assessment (indicating moderately ill)

Exclusion Criteria:

  • Subject has previously participated in this study or has received previous treatment with Rotigotine
  • Subject has participated in another study of an investigational medicinal product (IMP) or a medical device within the last 30 days prior to Visit 1, or is currently participating in another study of an IMP or a medical device
  • Subject has secondary RLS (eg, due to Renal Insufficiency [Uremia], Iron Deficiency Anemia or Rheumatoid Arthritis)
  • Subject has had a Ferritin value of ≤ 18 µg/L within the last 3 months prior to Baseline (Visit 2)
  • Subject has RLS associated with previous or concomitant therapy with Dopamine 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 evidence of an Impulse Control Disorder according to the Modified Minnesota Impulsive Disorders Interview (mMIDI) at Screening (Visit 1)
  • 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 Polysomnography (PSG) (local PSG evaluations) or evidenced by subject history
  • Subject has a 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 Suicide Severity Rating Scale (C-SSRS) at Screening (Visit 1)
  • 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, 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 last 12 months prior to Visit 1
  • Subject has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the subject's well being or ability to participate in this study
  • Subject has a clinically relevant Venous or Arterial Peripheral Vascular Disease
  • Subject has a malignant Neoplastic Disease requiring therapy within 12 months prior to Screening (Visit 1)
  • Subject is currently receiving treatment with any of the following drug classes: Neuroleptics, Hypnotics, Antidepressants, Anxiolytic Drugs, Anticonvulsive Therapy, Budipine, Dopamine Antagonist Antiemetics (except Domperidone), Opioids, Benzodiazepines, Monoamine Oxidase (MAO) Inhibitors, Catechol-O-Methyltransferase (COMT) Inhibitors, Sedative Antihistamines, Psychostimulates, or Amphetamines. If subject has received such therapy, a Washout Period of at least 7 days prior to Baseline (Visit 2) is required before starting treatment in this study
  • 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 medically acceptable methods of contraception, including at least 1 barrier method, unless sexually abstinent
  • Subject is a shift worker or performs other continuous non-disease-related life conditions which do not allow regular sleep at night
  • At Screening Visit (Visit 1) or Baseline Visit (Visit 2), subject has Symptomatic Orthostatic Hypotension with a decrease of Blood Pressure (BP) from supine to standing position of ≥ 20 mmHg in systolic BP or of ≥ 10 mmHg in diastolic BP taken from the 5-minute supine and 1- and/or 3-minute standing measurements at Visit 1 or Visit 2
  • Subject is treated with Dopamine Agonists within a period of 7 days prior to Baseline (Visit 2) or L-Dopa within 3 days prior to Baseline (Visit 2)
  • Subject has a known history indicating intolerability to prior Dopaminergic therapy (if pretreated) when previously treated with any Dopaminergic agent
  • Subject has a known hypersensitivity to any components of the study medication, such as a history of significant skin hypersensitivity to adhesives, known hypersensitivity to other transdermal medications, or has 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: NCT01569464

Locations
United States, Alabama
006
Birmingham, Alabama, United States
013
Jasper, Alabama, United States
United States, Arizona
021
Gilbert, Arizona, United States
United States, Arkansas
014
Little Rock, Arkansas, United States
United States, California
010
Oceanside, California, United States
004
Orange, California, United States
United States, Florida
002
Tampa, Florida, United States
United States, Georgia
012
Macon, Georgia, United States
United States, Louisiana
008
Destrehan, Louisiana, United States
United States, Massachusetts
017
Brighton, Massachusetts, United States
016
Brockton, Massachusetts, United States
United States, Michigan
019
Kalamazoo, Michigan, United States
United States, Missouri
015
St. Louis, Missouri, United States
United States, New York
007
West Seneca, New York, United States
United States, Ohio
018
Cincinnati, Ohio, United States
United States, Pennsylvania
009
West Chester, Pennsylvania, United States
United States, Texas
003
Austin, Texas, United States
005
San Antonio, Texas, United States
Sponsors and Collaborators
UCB, Inc.
Investigators
Study Director: UCB Clinical Trial Call Center 1-877-822-9493
  More Information

No publications provided

Responsible Party: UCB, Inc.
ClinicalTrials.gov Identifier: NCT01569464     History of Changes
Other Study ID Numbers: RL0003
Study First Received: March 30, 2012
Last Updated: June 13, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by UCB, Inc.:
Rotigotine
Restless Legs Syndrome
Neupro®

Additional relevant MeSH terms:
Restless Legs Syndrome
Psychomotor Agitation
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Nervous System Diseases
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 July 28, 2014