Effects of Neupro on Cardiovascular Observations in Patie... | NCT01455012

NCT01455012

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

ID	Type	Description	Link
2011-000053-23	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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	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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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
At Screening Visit or Baseline Visit subject has symptomatic orthostatic hypotension
Subject is treated with dopamine agonists within a period of 14 days prior to Baseline or L-dopa within 7 days prior to Baseline
Subject has a medical history indicating intolerability to prior dopaminergic therapy (if pretreated)
Subject has received previous treatment with Rotigotine
Subject has participated in another study of an investigational drug or device within the 28 days prior to Visit 2 (Baseline) or is currently participating in another study of an investigational drug
Subject has a 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 has unresolved contact dermatitis
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)

Contacts/Locations Module

Name	Affiliation	Role
UCB Clinical Trial Call Center	+1 877 822 9493 (UCB)	Study Director

References Module

Label	URL
FDA Safety Alerts and Recalls	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Participant Flow refers to the Randomized Set (RS). RS consists of all subjects randomized into this study.

Arm/Group Information

ID	Title	Description
FG000	Placebo	Placebo Placebo : 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.
FG001	Rotigotine	Rotigotine, optimal dose (minimum dose 1 mg/24 h, maximum dose 3 mg/24 h) Rotigotine : 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.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG00041 subjects FG00140 subjects
COMPLETED		FG00030 subjects FG00136 subjects
NOT COMPLETED		FG00011 subjects FG0014 subjects

Type	Comment	Reasons
Adverse Event		FG0000 subjects FG0012 subjects
Lack of Efficacy		FG0006 subjects FG001

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Placebo	Placebo Placebo : 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.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	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.	Full Analysis Set (FAS) includes all randomized subjects having both a Baseline and a post-Baseline measurement for the primary efficacy variable. All 66 subjects in the FAS are included in the analysis of this Outcome Measure.	Posted		Least Squares Mean	95% Confidence Interval	Nocturnal Elevations of Systolic BP		Baseline to the end of the 4-week Maintenance Period

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Placebo Placebo : 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.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 9.1	Non-systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
UCB Clinical Trial Call Center	UCB	+1 877 822 9493 (UCB)

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

ID	Term
D012148	Restless Legs Syndrome

ID	Term
D009422	Nervous System Diseases
D020919	Sleep Disorders, Intrinsic
D020920	Dyssomnias
D012893	Sleep Wake Disorders

Intervention Browse Module

ID	Term
C047508	rotigotine

Masking Info

EG0003 events3 affected40 at risk

EG00111 events9 affected40 at risk

Facility	Status	City	State	ZIP	Country	Contacts
		Berlin			Germany