ATLANTA, April 25, 2012 /PRNewswire/ -- New post-hoc analyses of pivotal clinical trials of Neupro® (rotigotine transdermal system) in patients with Restless Legs Syndrome (RLS)/Willis Ekbom disease analysed the severity and impact of RLS symptoms using changes in individual International RLS Study Group Rating Scale (IRLS) item scores. Improvements with rotigotine versus placebo were observed in most of the single items from the IRLS, which measures sensory-motor dysfunction, severity of sleep disturbance, and impact of RLS on daily activities. The findings from the post-hoc analyses of the two pivotal trials carried out in US and Europe were presented today at the 64th American Academy of Neurology (AAN) Annual Meeting in New Orleans, LA.
"The total score of the IRLS is usually reported in clinical trials. These post-hoc analyses used a new approach and evaluated the core symptoms of RLS using single item data from the IRLS," said Dr. Richard Allen, Johns Hopkins University, Baltimore, MD. "The results suggested that rotigotine's effects appear to be related both to its broad action in improving core RLS symptoms and on reducing impact on sleep and daily activities. Additional prospective studies are needed to further our understanding in this area."
The post-hoc analyses were based on data from the two phase III, double-blind, 6 month placebo-controlled trials (SP792 in the U.S. [NCT00135993] and SP790 in Europe [NCT00136045]). They investigated the effect of rotigotine on specific features of RLS by examining single item scores from IRLS related to core RLS symptoms (sensory-motor dysfunction), degree of severity (days and hours within day with symptom), and symptom impact on sleep, mood and daily life.
The IRLS total score consists of 10 single items:
- Item 1: RLS discomfort in legs or arms
- Item 2: need to move around due to RLS symptoms
- Item 3: relief of leg or arm discomfort from moving around
- Item 4: severity of sleep disturbance due to RLS symptoms
- Item 5: tiredness or sleepiness during the day due to RLS symptoms
- Item 6: severity of RLS as a whole
- Item 7: frequency of RLS symptoms
- Item 8: average severity when RLS symptoms occurred
- Item 9: impact on ability to carry out daily affairs
- Item 10: severity of mood disturbance due to RLS symptoms
In these post-hoc analyses, the severity and impact of RLS symptoms were analysed using mean change from baseline to end of maintenance in individual IRLS item scores. Results presented below should be viewed in the context of the post-hoc analyses. In addition the p-values reported are exploratory and additional prospective studies are needed to further our understanding in this area.
Post-hoc analysis of the European study (SP790)
In the post-hoc analysis of the European study improvements were observed with rotigotine versus placebo in 9 of 10 individual IRLS items as listed below:
Core RLS symptoms
- Discomfort in legs or arms (treatment difference [LS mean (95% confidence interval)]: -0.8 [-1.1, -0.6]); p<0.0001
- Need to move around: (-0.8 [-1.1,-0.5]); p<0.0001
- Severity of RLS as a whole: (-0.8 [-1.1, -0.6]); p<0.0001
- Average severity when symptoms occurred: (-0.7 [-1.0, -0.5]); p<0.0001
- Frequency of symptoms: (-1.0 [-1.3, -0.6]); p<0.0001
Improvements in relief of 'RLS discomfort by movement' were numerically greater with rotigotine transdermal system versus placebo but did not reach significance (-0.1 [-0.3, 0.0], p=0.1216.
Impact of RLS symptoms
- Severity of sleep disturbance: (-0.9 [-1.1, -0.6]); p<0.0001
- Tiredness or sleepiness during the day: (-0.5 [-0.8, -0.3]); p<0.0001
- Impact on ability to carry out daily affairs: (-0.6 [-0.8, -0.3); p<0.0001
- Severity of mood disturbance: (-0.6 [-0.9, -0.4]); p<0.0001
Post-hoc analysis of the US study (SP792)
In the post-hoc analysis of the US study improvements were observed with rotigotine versus placebo in 9 of 10 individual IRLS items as listed below:
Core RLS symptoms
- Discomfort in legs or arms (treatment difference [LS mean (95% confidence interval)]): (-0.4 [-0.6, -0.2]), p=0.0009
- Need to move around: (-0.5 [-0.7, -0.2]), p=0.0002
- Relief of RLS discomfort by movement: (-0.4 [-0.6, -0.1]), p=0.0017
- Severity of RLS as a whole: (-0.4 [-0.6, -0.2]), p=0.0003
- Average severity when symptoms occurred: (-0.5 [-0.7, -0.2]), p<0.0001
- Frequency of symptoms: (-0.9 [-1.2, -0.6]), p<0.0001
Impact of RLS symptoms
- Severity of sleep disturbance: (-0.4 [-0.6, -0.1]), p=0.0026
- Tiredness or sleepiness during the day: (-0.3 [-0.5, -0.1]), p=0.0066
- Impact on ability to carry out daily affairs: (-0.3 [-0.4, 0.1]), p=0.0021
Improvements in 'severity of mood disturbance due to RLS symptoms' were numerically greater with rotigotine versus placebo but did not reach significance (-0.1 [-0.3, 0.0]), p=0.1536.
Notes to Editors
About Neupro® in the U.S.
Neupro® (Rotigotine Transdermal System) is indicated for the treatment of the signs and symptoms of idiopathic Parkinson's disease and moderate-to-severe primary Restless Legs Syndrome (RLS). For more information about Neupro visit www.neupro.com.
Neupro® in the U.S. Important Safety Information
Neupro® contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life threatening or less severe asthmatic episodes in certain susceptible people.
Patients treated with Neupro® have reported falling asleep while engaged in activities of daily living and somnolence. In clinical trials for the highest recommended Neupro® dose, the incidence of the treatment difference between Neupro® and placebo for somnolence was 16% for early-stage Parkinson's disease, 4% for advanced-stage Parkinson's disease, and 6% for Restless Legs Syndrome. Some patients perceived no warnings signs, such as excessive drowsiness. Patients should be advised to exercise caution while driving, operating heavy machinery or working at heights during treatment with Neupro®.
There is an increased risk for hallucinations in patients with advanced-stage Parkinson's disease treated with Neupro®. In clinical trials for the highest recommended Neupro® dose, the incidence of the treatment difference between Neupro® and placebo for hallucinations was 4%, and this difference increased with increasing dose. Patients also may experience new or worsening mental status and behavioral changes, which may be severe, including psychotic-like behavior during Neupro® treatment or after starting or increasing the dose of Neupro®.
Neupro® may cause symptomatic postural/orthostatic hypotension and syncope, especially during dose escalation, elevated blood pressure, elevated heart rate, weight gain and fluid retention. Neupro® should be used with caution in patients with severe cardiovascular disease.
Case reports suggest that patients can experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge eating, and other intense urges, and the inability to control these urges while taking medications, including Neupro®, that increase central dopaminergic tone and that are generally used for the treatment of Parkinson's disease. Patients should be monitored for the development of new or increased urges while being treated with Neupro®. Dose reduction or discontinuation of Neupro® should be considered if such urges develop.
Neupro® may increase the dopaminergic side effects of levodopa and may cause and/or exacerbate pre-existing dyskinesia. In clinical trials for the highest recommended Neupro® dose, the incidence of the treatment difference between Neupro® and placebo for dyskinesia was 7% for advanced-stage Parkinson's disease, and this difference increased with increasing dose.
Neupro® can cause application site reactions, and some may be severe. In clinical trials for the highest recommended Neupro® dose, the incidence of the treatment difference between Neupro® and placebo for application site reactions was 15% for early-stage Parkinson's disease, 23% for advanced-stage Parkinson's disease, and 39% for Restless Legs Syndrome. Most reactions were mild or moderate in intensity and were limited to the patch area.
Patients with Parkinson's disease have a higher risk of developing melanoma than the general population. Patients should be monitored for melanomas frequently when using Neupro®. Dopaminergic medicinal products, including Neupro®, may cause augmentation and rebound in RLS patients.
The most common adverse reactions (greater than or equal to 5% greater than placebo) for the highest recommended doses of Neupro® for treatment of Parkinson's disease are nausea, vomiting, somnolence, application site reactions, dizziness, anorexia, hyperhidrosis, and insomnia. The most common adverse reactions (greater than or equal to 5% greater than placebo) for the highest recommended dose of Neupro® for treatment of Restless Legs Syndrome are application site reactions, nausea, somnolence, and headache.
Additional important safety information for Neupro® can be accessed at www.neupro.com/pi.
Notes to Editors
About Neupro® in the European Union
Neupro® (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 occur (end of dose or on-off fluctuations). Neupro® is also approved in the European Union for the symptomatic treatment of moderate to severe idiopathic Restless Legs Syndrome in adults.
Neupro® in the European Union Important Safety Information
Neupro® 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. Neupro® should be removed if the patient has to undergo MRI or cardioversion to avoid skin burns.
It is recommended to monitor blood pressure, especially at the beginning of treatment, due to the risk of postural/orthostatic hypotension associated with dopaminergic therapy and reported during Neupro® treatment.Neupro® has been associated with somnolence and episodes of sudden sleep onset. Patients treated with dopamine agonists including Neupro®, have been reported 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.
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 Neupro® is observed, Neupro® 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 Neupro®.
Neupro® 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.
Neupro® should not be used during pregnancy. Breast-feeding should be discontinued.
In restless legs syndrome augmentation may occur. Augmentation refers to the earlier onset of symptoms in the evening (or even the afternoon), increase in severity of symptoms, and spread of symptoms to involve other body parts.
At the beginning of therapy, dopaminergic adverse reactions, such as nausea and vomiting, may occur. These are usually mild or moderate in intensity and transient, even if treatment is continued.
Adverse drug reactions reported in more than 10% of Parkinson's patients treated with Neupro® are nausea, vomiting, application site reactions, somnolence, dizziness and headache. The majority of these application site reactions are mild or moderate in intensity.
Adverse drug reactions reported in more than 10% of RLS patients treated with Neupro® are nausea, application site reactions, asthenic conditions (including fatigue, asthenia, malaise) and headache. The majority of these application site reactions are mild or moderate in intensity.
All Neupro® supply should be stored in a refrigerator (2 degrees C-8 degrees C). There is no need for patients to transport Neupro® 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 (Revised August 2011):
For further information
Andrea Levin, Associate Director, Public Relations and Communications, UCB
T +1.770.970.8352, [email protected]
Eimear O'Brien, Director, Brand Communications, UCB
T +32.2.559.9271, [email protected]
Antje Witte, Investor Relations, UCB
T +32.2.559.9414, [email protected]
France Nivelle, Global Communications, UCB
T +32.2.559.9178, [email protected]
UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With more than 8,500 people in about 40 countries, the company generated revenue of EUR 3.2 billion in 2011. UCB is listed on Euronext Brussels (symbol: UCB).
Forward looking statements
This press release contains forward-looking statements based on current plans, estimates and beliefs of management. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial information, expected legal, political, regulatory or clinical results and other such estimates and results. By their nature, such forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and assumptions which could cause actual results to differ materially 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, the inability to obtain necessary regulatory approvals or to obtain them on acceptable terms, costs associated with research and development, changes in the prospects for products in the pipeline or under development by UCB, effects of future judicial decisions or governmental investigations, product liability claims, challenges to patent protection for products or product candidates, changes in laws or regulations, exchange rate fluctuations, changes or uncertainties in tax laws or the administration of such laws and hiring and retention of its employees. UCB is providing this information as of the date of this press release and expressly disclaims any duty to update any information contained in this press release, either to confirm the actual results or to report a change in its expectations.
There is no guarantee that new product candidates in the pipeline will progress to product approval or that new indications for existing products will be developed and approved. Products or potential products which are the subject of partnerships, joint ventures or licensing collaborations may be subject to differences between the partners. Also, UCB or others could discover safety, side effects or manufacturing problems with its products after they are marketed.
Moreover, sales may be impacted by international and domestic trends toward managed care and health care cost containment and the reimbursement policies imposed by third-party payers as well as legislation affecting biopharmaceutical pricing and reimbursement.