BRUSSELS, July 28 UCB today announced the results of a 6-month, randomized, double-blind, placebo-controlled clinical study, published in the journal Movement Disorders, showing that NeuproŽ (rotigotine transdermal system, 2 and 3 mg/24 hours) provided sustained, clinically relevant improvements in symptoms of Restless Legs Syndrome (RLS). The study also showed high rates of complete remission seen with rotigotine 2 mg or 3 mg/24 hours.
Advertisement
"In this study rotigotine alleviated RLS symptoms in patients with moderate to severe RLS over a treatment period of six months, which is the longest reported double-blind treatment period maintained in the U.S. for the evaluation of RLS treatments," said Dr. Richard Allen, from Department of Neurology, John Hopkins University, Baltimore, Md., U.S. "One result from this study was a high rate of complete remission from all RLS symptoms. Approximately one of three previously moderately to severely ill patients was without any RLS symptoms after 6 months of treatment with either 2 or 3 mg of rotigotine."
Advertisement
In the 6-month, double-blind study, 505 patients with moderate to severe RLS were randomized to receive either placebo or rotigotine (0.5, 1, 2, 3 mg/24 hours) by transdermal administration, of whom 494 patients (98%) were included in the modified intention-to-treat (mITT) analysis+. The two co-primary efficacy endpoints were decreased from baseline to end of maintenance in International Restless Legs Syndrome (IRLS)++ sum score and in Clinical Global Impressions (CGI-1) score. The IRLS sum score ranges from 0 (no symptoms) to 40 (very severe symptoms) and the CGI-1 from 1 (not ill at all) to 7 (extremely ill). Secondary efficacy variables included the proportion of treatment responders for IRLS and CGI-1.
On both primary efficacy measures, rotigotine 2 and 3 mg/24 hour was shown to produce a statistically significant and clinically relevant improvement compared to placebo (p < 0.001), with sustained improvement observed throughout the six months of maintenance. Treatment differences between placebo and rotigotine for the IRLS sum score were -4.5 (95% Confidence Interval: -6.9, -2.2) for 2 mg/24 hour rotigotine, -5.2 (95% Confidence Interval: -7.5, -2.9) for 3 mg/24 hour rotigotine, and for CGI-1 -0.65 (95% Confidence Interval: -1.0, -0.3) and -0.9 (95% Confidence Interval: -1.3, -0.5) for the 2 and 3 mg/24 hour doses, respectively. Reductions in IRLS sum score and CGI-1 score were also seen with rotigotine 0.5 and 1 mg/24 hours, but differences from placebo were not statistically significant.
Secondary efficacy variables for IRLS or CGI-1 responders were defined by a minimum 50% improvement in the respective score at end of maintenance versus baseline. A total of 56.6% of all subjects receiving rotigotine were considered responders for the IRLS and 49.8% for CGI-1 score. In all rotigotine groups, responder rates were higher than in the placebo group and statistical significance was reached for the 1, 2 and 3 mg/24 hour doses. The number of patients needed to be treated with rotigotine instead of placebo for one of the patients to be classified as an IRLS responder was 4.4 and 3.4 for 2 and 3 mg/24 hour rotigotine, respectively, with similar numbers for CGI-1. An IRLS score of 0 (no symptoms) was documented for 9.1% of placebo and 23.3% of all rotigotine subjects (16.3% for 0.5 mg/24 hour, 17.2% for 1 mg/24 hour, 30.5% for 2 mg/24 hour and 29.1% for 3 mg/24 hour) with a number needed to treat of 4.7 for 2 mg/24 hour and 5.0 for 3 mg/24 hour rotigotine.
Most adverse events (AEs) were mild to moderate in intensity, the most common AEs being application site reactions (27% rotigotine versus 5% placebo), nausea (18.1% rotigotine versus 10% placebo) and headache (11.6% rotigotine versus 8% placebo).+++
+ The modified intention-to-treat (mITT) study population consisted of all randomly assigned patients with baseline data who received at least one dose of study medication and had at least one valid post-baseline set of data for both primary variables.
++ The International Restless Legs Syndrome Study Group Rating Scale (IRLS) is a ten-item scale developed and validated by The International Restless Legs Syndrome Study Group and considered to be the best scale for evaluating the severity and frequency of RLS symptoms and the degree to which they affect sleep and daily life. It is administered by clinicians and includes questions related to the severity of sensory and motor symptoms, sleep disturbance, daytime somnolence and impact of RLS on activities of daily living and mood.
+++ Please consult the NeuproŽ Summary of Product Characteristics for a full listing of adverse events.
Notes to Editors
About Restless Legs Syndrome
Restless Legs Syndrome (RLS) is a neurological disorder characterized by unpleasant sensations in the legs and an uncontrollable urge to move when at rest in order to relieve these feelings. It affects between 3 and 10% of the population to some extent. Most people with RLS have difficulty falling asleep and staying asleep. Left untreated the condition causes exhaustion and daytime fatigue. Many people with RLS report that their job, personal relations and activities of daily living are strongly affected as a result of their exhaustion. They are often unable to concentrate, have impaired memory, or fail to accomplish daily tasks. More than 80% of people with RLS also experience a more common condition known as periodic limb movement disorder (PLMD).
About NeuproŽ in the European Union
NeuproŽ (rotigotine) is approved in the European Union for the treatment of the signs and symptoms of early-stage idiopathic Parkinson's disease, as monotherapy (i.e. without levodopa) or in combination with levodopa, i.e. over the course of the disease, through to late stages when the effect of levodopa wears off or becomes inconsistent and fluctuations of the therapeutic effect occurs. NeuproŽ is also approved in the European Union for the symptomatic treatment of moderate to severe idiopathic restless legs syndrome in adults.
NeuproŽ in the European Union Important Safety Information
NeuproŽ is contraindicated in case of hypersensitivity to the active substance or to any of its excipients, and in case of magnetic resonance imaging (MRI) or cardioversion. NeuproŽ should be removed if the patient has to undergo MRI or cardioversion.
It is recommended to monitor blood pressure, especially at the beginning of treatment, due to the general risk of orthostatic hypotension associated with dopaminergic therapy.
NeuproŽ has been associated with somnolence episodes of sudden sleep onset episodes. Patients treated with dopamine agonists including NeuproŽ, have been reported as exhibiting signs of pathological gambling, increased libido and hypersexuality.
Symptoms suggestive of neuroleptic malignant syndrome have been reported with abrupt withdrawal of dopaminergic therapy. Therefore it is recommended to taper treatment.
NeuproŽ contains sodium metabisulphite, a sulphite that may cause allergic-type reactions including anaphylactic symptoms and life threatening or less severe asthmatic episodes in certain susceptible people.
Hallucinations have been reported, and patients should be informed that hallucinations can occur.
Cases of cardiopulmonary fibrotic complications have been reported in some patients treated with ergot-derived dopaminergic agents. Neuroleptics given as antiemetic should not be given to patients taking dopamine agonists. Ophthalmologic monitoring is recommended at regular intervals or if vision abnormalities occur.
External heat, from any source should not be applied to the area of the patch. Exposure of a skin rash or irritation to direct sunlight could lead to changes in the skin color. If a generalized skin reaction (e.g. allergic rash) associated with the use of NeuproŽ is observed, NeuproŽ should be discontinued.
Caution is advised when treating patients with severe hepatic impairment or acute worsening of renal function, a dose reduction might be needed.
The incidence of some dopaminergic adverse events, such as hallucinations, dyskinesia and peripheral oedema generally is higher when given in combination with L-dopa. This should be considered when prescribing NeuproŽ.
NeuproŽ should not be used during pregnancy. Breast-feeding should be discontinued.
Augmentation may occur in Restless Legs Syndrome patients. Augmentation refers to the earlier onset of symptoms in the evening (or early afternoon), increase in severity of symptoms and spread of symptoms to involve other body parts.
Adverse drug reactions reported in more than 10% of Parkinson's patients treated with NeuproŽ are nausea, vomiting, application site reactions, somnolence, dizziness and headache.
Adverse drug reactions reported in more than 10% of RLS patients treated with NeuproŽ are nausea, application site reactions, asthenic conditions and headache.
All NeuproŽ supply should be stored in a refrigerator. There is no need for patients to transport NeuproŽ patches in special containers and they must not be stored in a freezer compartment.
Please refer to the European Summary of Product Characteristics for full prescribing information (Approved 15th March 2010): http://www.emea.europa.eu/humandocs/PDFs/EPAR/neupro/emea-combined-h626en.pdf
About NeuproŽ in the U.S.
NeuproŽ (rotigotine transdermal system) is indicated in the U.S. for the treatment of the signs and symptoms of early-stage idiopathic Parkinson's disease. In April 2008, UCB recalled NeuproŽ from the U.S. market after ongoing monitoring revealed that specific batches of NeuproŽ had deviated from their approved specification. Recently the U.S. Food and Drug Administration (FDA) has recommended that UCB reformulate NeuproŽ patches and UCB is working on the development of a new formulation. Patients and physicians with questions about the status of NeuproŽ, or about UCB's Patient Access program for NeuproŽ, may contact UCB Medical Information at 1-866-822-0068 (option 9).
Important Safety Information - U.S.
Some patients treated with NeuproŽ reported falling asleep while engaged in activities of daily living, including operation of motor vehicles, which sometimes resulted in accidents. Some patients perceived no warning signs, such as excessive drowsiness. Hallucinations were reported in 2.0% of patients treated with NeuproŽ compared to 0.7% of patients on placebo. NeuproŽ contains metabisulfite. NeuproŽ should be used with caution in patients, especially those at risk for cardiovascular disease, because of the potential for symptomatic hypotension, syncope, elevated heart rate, elevated blood pressure, fluid retention and/or weight gain. All Parkinson's disease patients are at a higher risk for melanoma and should be monitored regularly. The most commonly reported side effects in clinical trials were nausea, application site reactions, somnolence, dizziness, headache, vomiting and insomnia. Some subjects who received NeuproŽ experienced a decline in blood hemoglobin levels (about 2% relative to subjects who received placebo). It is not known whether this change is readily reversible with discontinuation of NeuproŽ.
NeuproŽ is a registered trademark of the UCB Group of companies.
About UCB
UCB, Brussels, Belgium (www.ucb.com) is a biopharmaceutical company dedicated to the research, development and commercialization of innovative medicines with a focus on the fields of central nervous system and immunology disorders. Employing more than 9 000 people in over 40 countries, UCB produced revenue of EUR 3.1 billion in 2009. UCB is listed on Euronext Brussels (symbol: UCB).
Forward looking statement
This press release contains forward-looking statements based on current plans, estimates and beliefs of management. Such statements are subject to risks and uncertainties that may cause actual results to be materially different from those that may be implied by such forward-looking statements contained in this press release. Important factors that could result in such differences include: changes in general economic, business and competitive conditions, effects of future judicial decisions, changes in regulation, exchange rate fluctuations and hiring and retention of its employees.
For further information Eimear O Brien, Associate Director, Global CNS Communications T +32 2 559 9271, [email protected] Andrea Levin / Public Relations Manager, CNS, UCB, Inc. Office: 770.970.8352 /Mobile: 404.483.7329 /Email: [email protected]
SOURCE UCB
