Effects of Neupro on Cardiovascular Observations in Patients With Restless Legs Syndrome

NCT01455012 | Completed Phase 4 Results

• 2 other identifiers: SP09772011-000053-23
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 6

Brief Summary

Periodic Limb Movements (PLMs) during sleep in patients with Restless Legs Syndrome (RLS) have been shown to be associated with elevations in Blood Pressure (BP). Rotigotine has been shown to effectively reduce the incidence of PLMs in patients with RLS. The current study aims to demonstrate that treatment with Rotigotine could help reduce the number of nocturnal BP elevations associated with PLMs in patients with RLS.

Conditions

Restless Legs Syndrome

Keywords

Rotigotine; Neupro; RLS; Cardiovascular Risk; Nocturnal Blood Pressure

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the Number of Elevations of Systolic Blood Pressure (BP) During the Night That Are Associated With Periodic Limb Movements (PLMs) at the End of the 4-week Maintenance Period

  Polysomnography (PSG) recordings, including the assessment of continuous Blood Pressure and 12-lead Electrocardiogram (ECG), were obtained on 2 consecutive nights prior to Baseline Visit and prior to End of Maintenance Period (Visit 7) for up to 8 hours per night. Readings from the first night of the PSG were only used for analysis if the PSG from the second night was determined to be not valid for evaluation. Influence of Periodic Limb Movements (PLMs) on sleep is reflected in the Periodic Limb Movement-Related Arousal Index (PLMAI). Arousal is defined as sudden change in the EEG activity and the index illustrates to what degree the PLMs contribute to arousal from sleep. Sleep stages and time spent in each sleep stage were determined from Electroencephalogram (EEG) readings. A negative value in Change from Baseline indicates an improvement from Baseline. The higher the negative value the better the improvement.

  Baseline to the end of the 4-week Maintenance Period

Secondary Outcomes (13)

• Change From Baseline in the Total Number of Elevations of Systolic Blood Pressure (BP) During the Night at the End of the 4-week Maintenance Period

  Baseline to the end of the 4-week Maintenance Period

• Change From Baseline in the Periodic Limb Movements Index (PLMI) at the End of the 4-week Maintenance Period

  Baseline to the end of the 4-week Maintenance Period

• Change From Baseline in the International Restless Legs Syndrome Rating Scale (IRLS) at the End of the 4-week Maintenance Period

  Baseline to the end of the 4-week Maintenance Period

• Change From Baseline in Restless Legs Syndrome-Quality of Life (RLS-QoL) at the End of the 4-week Maintenance Period

  Baseline to the end of the 4-week Maintenance Period

• Clinical Global Impressions (CGI) Item 2 (Change of Condition) at the End of the 4-week Maintenance Period

  At the end of the 4-week Maintenance Period

Study Arms (2)

Rotigotine

EXPERIMENTAL

Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h)

Drug: Rotigotine

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Rotigotine DRUG

Rotigotine 1 mg/24 h, 2 mg/24 h, and 3 mg/24 h. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.

Rotigotine

Placebo DRUG

Matching Placebo. Subjects will be titrated to their optimal/maximal dose in weekly increments of 1 mg/24 h during a Titration Period. During Maintenance Period the subjects will continue on their optimal/maximal dose for 28 days. Following the Maintenance Period, subjects will be de-escalated over 7 days, depending on their optimal/maximal dose.

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:

• Subject is informed and given ample time and opportunity to think about her/his participation and give her/his written informed consent
• 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 able to apply/remove the study patch correctly
• Subject is male or female, and is ≥18 and ≤75 years of age
• Subject meets the diagnosis of idiopathic Restless Legs Syndrome (RLS) 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 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 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)
• Subject has a score of ≥11 on the RLS-Diagnostic Index (RLS-DI) (Benes and Kohnen, 2009)
• Subject has an initial response to previous dopaminergic treatment for RLS or has no previous dopaminergic treatment (ie, de novo)
• The subject's Body Mass Index (BMI) is ≥18 kg/m\^2 and ≤35 kg/m\^2
• At Baseline subject has a score of ≥15 on the IRLS (indicating moderate to severe RLS)
• At Baseline subject has a score of ≥4 points on the CGI Item 1 assessment (indicating moderately ill)
• At Baseline subject has a score of ≥15 PLM/h on the Periodic Limb Movements Index (PLMI) based on polysomnography (PSG) (recorded during the second night) as assessed by the investigator
• Subjects are on a concomitant dose of antihypertensives that is at a stable dose for at least 4 weeks prior to Baseline and hypertension is reasonably controlled while the subject agrees to continue at this dose for the duration of the study, or subject has not received concomitant treatment with antihypertensives for at least 4 weeks prior to Baseline and does not intend to start such use during the study

You may not qualify if:

• Subject has RLS due to renal insufficiency (uremia), iron deficiency anemia, or rheumatoid arthritis
• Subject has RLS associated with previous or concomitant therapy with dopamine D2 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 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 PSG (local PSG evaluations) or evidenced by subject history
• 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, akathisia, 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 previous 12 months
• Subject has any medical or psychiatric condition, which in the opinion of the investigator, can jeopardize or would compromise the subject's ability to participate in this study
• Subject has clinically relevant cardiac dysfunction and/or arrhythmias (eg, suspected conduction system dysregulations, second or third degree atrioventricular block, complete left or right bundle branch block, sick sinus syndrome, New York Heart Association Class III or IV congestive heart failure, or had a myocardial infarction within 12 months prior to Screening \[Visit 1\])
• Subject has 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 effective 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

Sponsors & Collaborators

• UCB BIOSCIENCES GmbH: lead

Study Sites (6)

Unknown Facility

Berlin, Germany

Location

Unknown Facility

Kassel, Germany

Location

Unknown Facility

Marburg, Germany

Location

Unknown Facility

München, Germany

Location

Unknown Facility

Münster, Germany

Location

Unknown Facility

Schwerin, Germany

Location

Related Links

• FDA Safety Alerts and Recalls

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: UCB Clinical Trial Call Center
• Organization: UCB

+1 877 822 9493 (UCB)

Study Officials

• UCB Clinical Trial Call Center

  +1 877 822 9493 (UCB)

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2011
• First Posted: October 19, 2011
• Study Start: September 1, 2011
• Primary Completion: May 1, 2012
• Study Completion: June 1, 2012
• Last Updated: July 26, 2013
• Results First Posted: July 18, 2013

Record last verified: 2013-07

Locations

DE (6)