Back to resultsRotigotine Effect on All-day Functioning and Quality of Life in Subjects With Moderate to Severe Restless Legs Syndrome (RLS) (RESTORE)
Primary Purpose
Restless Legs Syndrome
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Rotigotine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Restless Legs Syndrome focused on measuring Rotigotine, Restless Legs Syndrome, Neupro®
Eligibility 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
Sites / Locations
- 006
- 013
- 021
- 014
- 010
- 004
- 002
- 012
- 008
- 017
- 016
- 019
- 015
- 007
- 018
- 009
- 003
- 005
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Rotigotine
Placebo
Arm Description
Rotigotine patches titrated from 1 mg/ 24 hr - 3 mg /24 hr or until effective or maximum dose is reached.
Placebo patches titrated from 1 mg/ 24 hr - 3 mg/ 24 hr or until effective or maximum dose was reached. Placebo 1 mg/ 24 hr, Placebo 2 mg/ 24 hr, Placebo 3 mg/ 24 hr, one patch every 24 hours 7 weeks
Outcomes
Primary Outcome Measures
Change From Baseline To The End Of The Maintenance Period in International Restless Legs Scale (IRLS) Sum Score
The International Restless Legs Scale (IRLS) was 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 ranged from 0 (not present) to 4 (severe). A sum score across all 10 items was calculated for analysis, which varied 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)
The Multiple Suggested Immobilization Test Discomfort Scale (m-SIT-DS) was 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 ranged from 0 (no symptoms) to 10 (very severe symptoms) and were 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)
During each single Suggested Immobilization Test (SIT) PLMWI was measured using a validated actigraphy device. Simultaneous actigraphy of the legs was performed by an actigraphy device, which was attached to the ankle prior to the start of the SIT. The PLMWI was recorded while the subject was awake.
Scores ranged from 0 (no symptoms) to 10 (very severe symptoms) and were 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 Scales [RLS-6])
The RLS-6 is an 11-point scale. This 11-point scale was provided with ranges between (0 = completely satisfied) to (10 = completely dissatisfied).
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 Scales [RLS-6])
The RLS-6 is an 11-point scale. This 11-point scale was provided with ranges between (0 = none) to (10 = very severe).
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 Scales [RLS-6])
The RLS-6 is an 11-point scale. This 11-point scale was provided with ranges between (0 = none) to (10 = very severe).
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 Scales [RLS-6])
The RLS-6 is an 11-point scale. This 11-point scale was provided with ranges between (0 = none) to (10 = very severe).
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 Scales [RLS-6])
The RLS-6 is an 11-point scale. This 11-point scale was provided with ranges between (0 = none) to (10 = very severe).
Change In Item Score From Baseline To The End Of The Maintenance Period In Daytime Tiredness (Item 6 of Restless Legs Syndrome 6 Rating Scales [RLS-6])
The RLS-6 is an 11-point scale. This 11-point scale was provided with ranges between (0 = not at all) to (10 = very severe).
Change From Baseline To The End Of Maintenance Period In Daytime Somnolence Domain Score Of The Medical Outcomes Study (MOS) Sleep Scale - Revised (MOS Sleep-R)
The Medical Outcomes Study (MOS) Sleep Scale-Revised (MOS Sleep-R) is a self-administered questionnaire measuring several important aspects of sleep that have been validated in both general and patient populations.
The MOS Sleep-R consists of 12-items. Responses for 10 of the 12 items are on a 5-point frequency scale with options ranging from "all of the time" to "none of the time". The other two items ask about the length of time to fall asleep and the average number of hours slept per night. The sleep problems index I allows for the summary of sleep problems using an abbreviated six-item index, whereas the sleep problems index II uses nine of the 12 items of the scale to compute an overall sleep problem summary. A higher score on each scale in summary index represents a lack of sleep problems (better sleep quality). All scores are transformed linearly to range from 0 to 100, with the exception of the sleep quantity subscale, which is scored in hours.
Change From Baseline To The End of Maintenance Period In Sleep Disturbance Domain Score Of The Medical Outcomes Study (MOS) Sleep Scale - Revised (MOS Sleep-R)
The Medical Outcomes Study (MOS) Sleep Scale-Revised (MOS Sleep-R) is a self-administered questionnaire measuring several important aspects of sleep that have been validated in both general and patient populations.
The MOS Sleep-R consists of 12-items. Responses for 10 of the 12 items are on a 5-point frequency scale with options ranging from "all of the time" to "none of the time". The other two items ask about the length of time to fall asleep and the average number of hours slept per night. The sleep problems index I allows for the summary of sleep problems using an abbreviated six-item index, whereas the sleep problems index II uses nine of the 12 items of the scale to compute an overall sleep problem summary. A higher score on each scale in summary index represents a lack of sleep problems (better sleep quality). All scores are transformed linearly to range from 0 to 100, with the exception of the sleep quantity subscale, which is scored in hours.
Change From Baseline To The End of Maintenance Period In Sleep Adequacy Domain Score Of The Medical Outcomes Study (MOS) Sleep Scale - Revised (MOS Sleep-R)
The Medical Outcomes Study (MOS) Sleep Scale-Revised (MOS Sleep-R) is a self-administered questionnaire measuring several important aspects of sleep that have been validated in both general and patient populations.
The MOS Sleep-R consists of 12-items. Responses for 10 of the 12 items are on a 5-point frequency scale with options ranging from "all of the time" to "none of the time". The other two items ask about the length of time to fall asleep and the average number of hours slept per night. The sleep problems index I allows for the summary of sleep problems using an abbreviated six-item index, whereas the sleep problems index II uses nine of the 12 items of the scale to compute an overall sleep problem summary. A higher score on each scale in summary index represents a lack of sleep problems (better sleep quality). All scores are transformed linearly to range from 0 to 100, with the exception of the sleep quantity subscale, which is scored in hours.
Change From Baseline To The End of Maintenance Period In Sleep Quantity Domain Score Of The Medical Outcomes Study (MOS) Sleep Scale - Revised (Sleep Scale-R)
The Medical Outcomes Study (MOS) Sleep Scale-Revised (MOS Sleep-R) is a self-administered questionnaire measuring several important aspects of sleep that have been validated in both general and patient populations.
The MOS Sleep-R consists of 12-items. Responses for 10 of the 12 items are on a 5-point frequency scale with options ranging from "all of the time" to "none of the time". The other two items ask about the length of time to fall asleep and the average number of hours slept per night. The sleep problems index I allows for the summary of sleep problems using an abbreviated six-item index, whereas the sleep problems index II uses nine of the 12 items of the scale to compute an overall sleep problem summary. A higher score on each scale in summary index represents a lack of sleep problems (better sleep quality). All scores are transformed linearly to range from 0 to 100, with the exception of the sleep quantity subscale, which is scored in hours.
Change In Total Score From Baseline To The End of Maintenance Period On Profile Of Mood States Questionnaire (POMS)
The Profile of Mood States questionnaire (POMS) total score will be calculated as the sum of the scores for the following 5 scale scores (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Fatigue-Inertia, and Confusion-Bewilderment) and then subtracting the Vigor-Activity score. All factors have to be available for the total score to be calculated; otherwise the total score will be set to missing. The range for the POMS is 0 - 200 with a high score being negative and a low score being positive.
For the POMS questionnaire total score, descriptive statistics will be presented on both the observed and the change from Baseline to the end of the Maintenance Period values for the Full Analysis Set (FAS).
Change From Baseline in SF-36 Mental Component Summary Score
The SF-36 is a 36 item generic human research quality of life instrument that uses a recall period of 4 weeks. Items are grouped into 8 domains as follows: Physical Functioning (10 items), Role Physical (4 items), Bodily Pain (2 items), General Health (5 items), Vitality (4 items), Social Functioning (2 items), Role Emotional (3 items), Mental Health (5 items), and a further unscaled single item (question 2) for perceived stability or change in health (Health Transition) during the last year. The norm-based scores (based on the US general population) were used for analysis. For the MCS, the lowest and highest possible scores are -9 and 82 (rounded).
The SF-36 domains (subscores) are scored so that a higher score indicates a better health state.
Change From Baseline in SF-36 Physical Component Summary Score
The SF-36 is a 36 item generic human research quality of life instrument that uses a recall period of 4 weeks. Items are grouped into 8 domains as follows: Physical Functioning (10 items), Role Physical (4 items), Bodily Pain (2 items), General Health (5 items), Vitality (4 items), Social Functioning (2 items), Role Emotional (3 items), Mental Health (5 items), and a further unscaled single item (question 2) for perceived stability or change in health (Health Transition) during the last year. The norm-based scores (based on the US general population) were used for analysis. For the PCS, the lowest and highest possible scores are 1 and 81 (rounded).
The SF-36 domains (subscores) are scored so that a higher score indicates a better health state.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01569464
Brief Title
Rotigotine Effect on All-day Functioning and Quality of Life in Subjects With Moderate to Severe Restless Legs Syndrome (RLS)
Acronym
RESTORE
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
March 2012 (undefined)
Primary Completion Date
April 2013 (Actual)
Study Completion Date
April 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UCB Pharma
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Restless Legs Syndrome
Keywords
Rotigotine, Restless Legs Syndrome, Neupro®
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
150 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rotigotine
Arm Type
Active Comparator
Arm Description
Rotigotine patches titrated from 1 mg/ 24 hr - 3 mg /24 hr or until effective or maximum dose is reached.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo patches titrated from 1 mg/ 24 hr - 3 mg/ 24 hr or until effective or maximum dose was reached.
Placebo 1 mg/ 24 hr, Placebo 2 mg/ 24 hr, Placebo 3 mg/ 24 hr, one patch every 24 hours
7 weeks
Intervention Type
Drug
Intervention Name(s)
Rotigotine
Other Intervention Name(s)
Neupro®
Intervention Description
Transdermal patch containing Rotigotine formulated in an adhesive matrix. Subjects were to be treated with their optimal dose which consisted of one of the dose strengths below:
Rotigotine 1 mg /24 hr, Rotigotine 2 mg/ 24 hr, Rotigotine 3 mg/ 24 hr, One patch every 24 hours
7 weeks (titration plus maintenance)
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo patches titrated from 1 mg/ 24 hr - 3 mg/ 24 hr or until effective or maximum dose was reached.
Placebo 1 mg/ 24 hr, Placebo 2 mg/ 24 hr, Placebo 3 mg/ 24 hr, one patch every 24 hours.
7 weeks (titration plus maintenance)
Primary Outcome Measure Information:
Title
Change From Baseline To The End Of The Maintenance Period in International Restless Legs Scale (IRLS) Sum Score
Description
The International Restless Legs Scale (IRLS) was 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 ranged from 0 (not present) to 4 (severe). A sum score across all 10 items was calculated for analysis, which varied between 0 (no RLS symptoms present at all) to 40 (maximum severity in all symptoms).
Time Frame
Baseline to End of Maintenance Period (approximately 7 weeks)
Title
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)
Description
The Multiple Suggested Immobilization Test Discomfort Scale (m-SIT-DS) was 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 ranged from 0 (no symptoms) to 10 (very severe symptoms) and were assessed every 10 minutes within each SIT.
Time Frame
Baseline to End of Maintenance Period (approximately 7 weeks)
Secondary Outcome Measure Information:
Title
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)
Description
During each single Suggested Immobilization Test (SIT) PLMWI was measured using a validated actigraphy device. Simultaneous actigraphy of the legs was performed by an actigraphy device, which was attached to the ankle prior to the start of the SIT. The PLMWI was recorded while the subject was awake.
Scores ranged from 0 (no symptoms) to 10 (very severe symptoms) and were assessed every 10 minutes within each SIT.
Time Frame
Baseline to End of Maintenance Period (approximately 7 weeks)
Title
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 Scales [RLS-6])
Description
The RLS-6 is an 11-point scale. This 11-point scale was provided with ranges between (0 = completely satisfied) to (10 = completely dissatisfied).
Time Frame
Baseline to End of Maintenance Period (approximately 7 weeks)
Title
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 Scales [RLS-6])
Description
The RLS-6 is an 11-point scale. This 11-point scale was provided with ranges between (0 = none) to (10 = very severe).
Time Frame
Baseline to End of Maintenance Period (approximately 7 weeks)
Title
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 Scales [RLS-6])
Description
The RLS-6 is an 11-point scale. This 11-point scale was provided with ranges between (0 = none) to (10 = very severe).
Time Frame
Baseline to End of Maintenance Period (approximately 7 weeks)
Title
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 Scales [RLS-6])
Description
The RLS-6 is an 11-point scale. This 11-point scale was provided with ranges between (0 = none) to (10 = very severe).
Time Frame
Baseline to End of Maintenance Period (approximately 7 weeks)
Title
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 Scales [RLS-6])
Description
The RLS-6 is an 11-point scale. This 11-point scale was provided with ranges between (0 = none) to (10 = very severe).
Time Frame
Baseline to End of Maintenance Period (approximately 7 weeks)
Title
Change In Item Score From Baseline To The End Of The Maintenance Period In Daytime Tiredness (Item 6 of Restless Legs Syndrome 6 Rating Scales [RLS-6])
Description
The RLS-6 is an 11-point scale. This 11-point scale was provided with ranges between (0 = not at all) to (10 = very severe).
Time Frame
Baseline to End of Maintenance Period (approximately 7 weeks)
Title
Change From Baseline To The End Of Maintenance Period In Daytime Somnolence Domain Score Of The Medical Outcomes Study (MOS) Sleep Scale - Revised (MOS Sleep-R)
Description
The Medical Outcomes Study (MOS) Sleep Scale-Revised (MOS Sleep-R) is a self-administered questionnaire measuring several important aspects of sleep that have been validated in both general and patient populations.
The MOS Sleep-R consists of 12-items. Responses for 10 of the 12 items are on a 5-point frequency scale with options ranging from "all of the time" to "none of the time". The other two items ask about the length of time to fall asleep and the average number of hours slept per night. The sleep problems index I allows for the summary of sleep problems using an abbreviated six-item index, whereas the sleep problems index II uses nine of the 12 items of the scale to compute an overall sleep problem summary. A higher score on each scale in summary index represents a lack of sleep problems (better sleep quality). All scores are transformed linearly to range from 0 to 100, with the exception of the sleep quantity subscale, which is scored in hours.
Time Frame
Baseline to End of Maintenance Period (approximately 7 weeks)
Title
Change From Baseline To The End of Maintenance Period In Sleep Disturbance Domain Score Of The Medical Outcomes Study (MOS) Sleep Scale - Revised (MOS Sleep-R)
Description
The Medical Outcomes Study (MOS) Sleep Scale-Revised (MOS Sleep-R) is a self-administered questionnaire measuring several important aspects of sleep that have been validated in both general and patient populations.
The MOS Sleep-R consists of 12-items. Responses for 10 of the 12 items are on a 5-point frequency scale with options ranging from "all of the time" to "none of the time". The other two items ask about the length of time to fall asleep and the average number of hours slept per night. The sleep problems index I allows for the summary of sleep problems using an abbreviated six-item index, whereas the sleep problems index II uses nine of the 12 items of the scale to compute an overall sleep problem summary. A higher score on each scale in summary index represents a lack of sleep problems (better sleep quality). All scores are transformed linearly to range from 0 to 100, with the exception of the sleep quantity subscale, which is scored in hours.
Time Frame
Baseline to End of Maintenance Period (approximately 7 weeks)
Title
Change From Baseline To The End of Maintenance Period In Sleep Adequacy Domain Score Of The Medical Outcomes Study (MOS) Sleep Scale - Revised (MOS Sleep-R)
Description
The Medical Outcomes Study (MOS) Sleep Scale-Revised (MOS Sleep-R) is a self-administered questionnaire measuring several important aspects of sleep that have been validated in both general and patient populations.
The MOS Sleep-R consists of 12-items. Responses for 10 of the 12 items are on a 5-point frequency scale with options ranging from "all of the time" to "none of the time". The other two items ask about the length of time to fall asleep and the average number of hours slept per night. The sleep problems index I allows for the summary of sleep problems using an abbreviated six-item index, whereas the sleep problems index II uses nine of the 12 items of the scale to compute an overall sleep problem summary. A higher score on each scale in summary index represents a lack of sleep problems (better sleep quality). All scores are transformed linearly to range from 0 to 100, with the exception of the sleep quantity subscale, which is scored in hours.
Time Frame
Baseline to End of Maintenance Period (approximately 7 weeks)
Title
Change From Baseline To The End of Maintenance Period In Sleep Quantity Domain Score Of The Medical Outcomes Study (MOS) Sleep Scale - Revised (Sleep Scale-R)
Description
The Medical Outcomes Study (MOS) Sleep Scale-Revised (MOS Sleep-R) is a self-administered questionnaire measuring several important aspects of sleep that have been validated in both general and patient populations.
The MOS Sleep-R consists of 12-items. Responses for 10 of the 12 items are on a 5-point frequency scale with options ranging from "all of the time" to "none of the time". The other two items ask about the length of time to fall asleep and the average number of hours slept per night. The sleep problems index I allows for the summary of sleep problems using an abbreviated six-item index, whereas the sleep problems index II uses nine of the 12 items of the scale to compute an overall sleep problem summary. A higher score on each scale in summary index represents a lack of sleep problems (better sleep quality). All scores are transformed linearly to range from 0 to 100, with the exception of the sleep quantity subscale, which is scored in hours.
Time Frame
Baseline to End of Maintenance Period (approximately 7 weeks)
Title
Change In Total Score From Baseline To The End of Maintenance Period On Profile Of Mood States Questionnaire (POMS)
Description
The Profile of Mood States questionnaire (POMS) total score will be calculated as the sum of the scores for the following 5 scale scores (Tension-Anxiety, Depression-Dejection, Anger-Hostility, Fatigue-Inertia, and Confusion-Bewilderment) and then subtracting the Vigor-Activity score. All factors have to be available for the total score to be calculated; otherwise the total score will be set to missing. The range for the POMS is 0 - 200 with a high score being negative and a low score being positive.
For the POMS questionnaire total score, descriptive statistics will be presented on both the observed and the change from Baseline to the end of the Maintenance Period values for the Full Analysis Set (FAS).
Time Frame
Baseline to End of Maintenance Period (approximately 7 weeks)
Title
Change From Baseline in SF-36 Mental Component Summary Score
Description
The SF-36 is a 36 item generic human research quality of life instrument that uses a recall period of 4 weeks. Items are grouped into 8 domains as follows: Physical Functioning (10 items), Role Physical (4 items), Bodily Pain (2 items), General Health (5 items), Vitality (4 items), Social Functioning (2 items), Role Emotional (3 items), Mental Health (5 items), and a further unscaled single item (question 2) for perceived stability or change in health (Health Transition) during the last year. The norm-based scores (based on the US general population) were used for analysis. For the MCS, the lowest and highest possible scores are -9 and 82 (rounded).
The SF-36 domains (subscores) are scored so that a higher score indicates a better health state.
Time Frame
Baseline to End of Maintenance Period (approximately 7 weeks)
Title
Change From Baseline in SF-36 Physical Component Summary Score
Description
The SF-36 is a 36 item generic human research quality of life instrument that uses a recall period of 4 weeks. Items are grouped into 8 domains as follows: Physical Functioning (10 items), Role Physical (4 items), Bodily Pain (2 items), General Health (5 items), Vitality (4 items), Social Functioning (2 items), Role Emotional (3 items), Mental Health (5 items), and a further unscaled single item (question 2) for perceived stability or change in health (Health Transition) during the last year. The norm-based scores (based on the US general population) were used for analysis. For the PCS, the lowest and highest possible scores are 1 and 81 (rounded).
The SF-36 domains (subscores) are scored so that a higher score indicates a better health state.
Time Frame
Baseline to End of Maintenance Period (7 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
UCB Clinical Trial Call Center
Organizational Affiliation
1-877-822-9493
Official's Role
Study Director
Facility Information:
Facility Name
006
City
Birmingham
State/Province
Alabama
Country
United States
Facility Name
013
City
Jasper
State/Province
Alabama
Country
United States
Facility Name
021
City
Gilbert
State/Province
Arizona
Country
United States
Facility Name
014
City
Little Rock
State/Province
Arkansas
Country
United States
Facility Name
010
City
Oceanside
State/Province
California
Country
United States
Facility Name
004
City
Orange
State/Province
California
Country
United States
Facility Name
002
City
Tampa
State/Province
Florida
Country
United States
Facility Name
012
City
Macon
State/Province
Georgia
Country
United States
Facility Name
008
City
Destrehan
State/Province
Louisiana
Country
United States
Facility Name
017
City
Brighton
State/Province
Massachusetts
Country
United States
Facility Name
016
City
Brockton
State/Province
Massachusetts
Country
United States
Facility Name
019
City
Kalamazoo
State/Province
Michigan
Country
United States
Facility Name
015
City
St. Louis
State/Province
Missouri
Country
United States
Facility Name
007
City
West Seneca
State/Province
New York
Country
United States
Facility Name
018
City
Cincinnati
State/Province
Ohio
Country
United States
Facility Name
009
City
West Chester
State/Province
Pennsylvania
Country
United States
Facility Name
003
City
Austin
State/Province
Texas
Country
United States
Facility Name
005
City
San Antonio
State/Province
Texas
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
26569149
Citation
Garcia-Borreguero D, Allen R, Hudson J, Dohin E, Grieger F, Moran K, Schollmayer E, Smit R, Winkelman J. Effects of rotigotine on daytime symptoms in patients with primary restless legs syndrome: a randomized, placebo-controlled study. Curr Med Res Opin. 2016;32(1):77-85. doi: 10.1185/03007995.2015.1103216. Epub 2015 Nov 16.
Results Reference
derived
Learn more about this trial
Rotigotine Effect on All-day Functioning and Quality of Life in Subjects With Moderate to Severe Restless Legs Syndrome (RLS)
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