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

NCT01569464 | Completed Phase 3 Results

• 1 other identifier: RL0003
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 18

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.

Conditions

Restless Legs Syndrome

Keywords

Rotigotine; Restless Legs Syndrome; Neupro®

Outcome Measures

Primary Outcomes (2)

• 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).

  Baseline to End of Maintenance Period (approximately 7 weeks)

• 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.

  Baseline to End of Maintenance Period (approximately 7 weeks)

Secondary Outcomes (14)

• 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)

  Baseline to End of Maintenance Period (approximately 7 weeks)

• 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])

  Baseline to End of Maintenance Period (approximately 7 weeks)

• 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])

  Baseline to End of Maintenance Period (approximately 7 weeks)

• 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])

  Baseline to End of Maintenance Period (approximately 7 weeks)

• 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])

  Baseline to End of Maintenance Period (approximately 7 weeks)

Study Arms (2)

Rotigotine

ACTIVE COMPARATOR

Rotigotine patches titrated from 1 mg/ 24 hr - 3 mg /24 hr or until effective or maximum dose is reached.

Drug: Rotigotine

Placebo

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Rotigotine DRUG

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)

Also known as: Neupro®

Rotigotine

Placebo OTHER

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)

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):
• \. 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)
• \. The urge to move or unpleasant sensations begin or worsen during periods of rest or inactivity such as lying down or sitting
• \. 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
• \. 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?)

You may not qualify if:

• 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

Sponsors & Collaborators

• UCB Pharma: lead

Study Sites (18)

006

Birmingham, Alabama, United States

Location

013

Jasper, Alabama, United States

Location

021

Gilbert, Arizona, United States

Location

014

Little Rock, Arkansas, United States

Location

010

Oceanside, California, United States

Location

004

Orange, California, United States

Location

002

Tampa, Florida, United States

Location

012

Macon, Georgia, United States

Location

008

Destrehan, Louisiana, United States

Location

017

Brighton, Massachusetts, United States

Location

016

Brockton, Massachusetts, United States

Location

019

Kalamazoo, Michigan, United States

Location

015

St Louis, Missouri, United States

Location

007

West Seneca, New York, United States

Location

018

Cincinnati, Ohio, United States

Location

009

West Chester, Pennsylvania, United States

Location

003

Austin, Texas, United States

Location

005

San Antonio, Texas, United States

Location

Related Publications (1)

• 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.

  PMID: 26569149 DERIVED

MeSH Terms

Conditions

Restless Legs Syndrome

Interventions

rotigotine

Condition Hierarchy (Ancestors)

Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Parasomnias; Mental Disorders

Results Point of Contact

• Title: Study Director
• Organization: UCB Clinical Trial Call Center

+1 887 822 9493

Study Officials

• UCB Clinical Trial Call Center

  1-877-822-9493

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2012
• First Posted: April 3, 2012
• Study Start: March 1, 2012
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: August 26, 2014
• Results First Posted: August 26, 2014

Record last verified: 2014-08

Locations

US (18)