Neupro® (Rotigotine) Provided Clinically Relevant Improvements in Health-Related Quality of Life for People with Parkinson's Disease

BRUSSELS, Sept. 30 /PRNewswire/ -- People with Parkinson's disease who used once-daily Neupro® (rotigotine) in the RECOVER trial achieved improvements in quality of life, in addition to previously reported beneficial effects on motor and non-motor symptoms.

Data presented this week at the 2nd World Parkinson Congress in Glasgow, UK, showed that Neupro® provided clinically relevant improvements in PDQ-8 score. This is a self-administered health-related quality of life questionnaire (HRQL) for Parkinson's disease comprising eight items – mobility, activities of daily living, emotional well-being, social support, cognition, communication, bodily discomfort and stigma.

"Data from the RECOVER trial demonstrated improvements in motor and non-motor symptoms for people living with Parkinson's disease as well as worthwhile changes in the quality of their everyday lives, including their daily activities, their emotional well being and their cognitive and communication abilities," said Herve Lilliu, Head of Health Outcomes and Access, UCB.

The RECOVER trial was a multicenter, multinational, double-blind, placebo-controlled study designed to assess the effects of rotigotine in controlling early morning motor function and non-motor symptoms that affect the everyday lives of people with early- and late-stage Parkinson's disease. Patients were randomized (2:1) to receive rotigotine (2-16 mg/24 h) or placebo during a titration period lasting up to 8 weeks, followed by a 4-week maintenance period.

PDQ-8 data were obtained from measurements taken at baseline and at the end of the 12 week study from 89 placebo- and 176 rotigotine-randomized patients. Mean change from baseline PDQ-8 total score was greater in the rotigotine group (-6.9 [SD: 11.9]) than the placebo group (-1.2 [SD: 13.7]; p<0.001). Both the rotigotine effect size (-0.41) and standardized response mean (-0.58) were moderate based on the Cohen definition of change (0.20 small, 0.50 moderate, and 0.80 large effect). In the placebo group, the effect size (-0.06) and standardized response mean (-0.09) were low.

In a study of Asian patients, the PDQ-8 minimal important difference (MID) – defined as the smallest difference in score that informed patients/proxies would perceive as important and would lead the patient or clinician to consider a change in therapy – has been shown to range from 5.8-7.4 points.

"The change from baseline in PDQ-8 score in the rotigotine group was within the previously established MID range, suggesting that patients in the current study would consider the improvement in HRQL achieved by rotigotine to be important. The effect sizes indicate that the PDQ-8 is a responsive instrument and that rotigotine has a clinically relevant effect on HRQL," concluded Mr. Lilliu.

In the RECOVER study, the most frequently reported adverse events were nausea (rotigotine 21%, placebo 9%), application site reactions (rotigotine 15%, placebo 4%), and dizziness (rotigotine 10%, placebo 6%). In general, 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.

Preclinical data showed rotigotine increased depth of sleep in rats

Preclinical data presented at the Congress showed that continuous administration of rotigotine or pulsatile L-DOPA had beneficial effects on wakefulness and sleep patterns in a rat model of Parkinson's disease, but only continuous rotigotine decreased the ratio of alpha to delta wave sleep during slow wave sleep, indicative of increased depth of sleep. To date the clinical significance of this finding has not been established.

The study was carried out to investigate the effects of rotigotine and pulsatile L-DOPA on sleep-wake patterns in a preclinical rat model of Parkinson's disease.

After two days of baseline recording, the study compared the effects of rotigotine administered as a slow-release formulation of 0.5 or 5 mg/kg every second day for 6 days and L-DOPA/benserazide administered daily at 10/7.5 mg/kg s.c., for 6 days in 6-OHDA lesioned rats.

Latency to slow wave sleep (SWS) and paradoxical sleep (REM) onset, duration of waking, SWS and REM sleep and the alpha and delta frequency ratio during SWS were analyzed off-line. No effects were seen with low dose rotigotine or with a placebo vehicle. Pulsatile L-DOPA and continuous rotigotine at 5 mg/kg caused an increase in active waking and a decrease in SWS duration. While L-DOPA had no effect on the alpha/delta power ratio, the high dose of continuous rotigotine decreased the alpha/delta ratio towards an increase in delta power during SWS.

Other UCB sponsored presentations at the 2nd World Parkinson Congress

Fresh insights into the lives of people living with Parkinson's disease, and their differing needs for information and support were reported in analyses sponsored by UCB and presented at the Congress:

• Lindvall S, Graham L, O'Brien E, Davis U. A Qualitative Assessment of the Educational and Support Needs of People Living with Parkinson's Disease
• Verhaeghe A. & Elleboudt L. Learning from Online Discussions about Parkinson's Disease Amongst People with Parkinson's and Their Carers
• Wullner U, Fuchs G, Reketat N, Randerath O, Kassubek J. Pharmacotherapy for Parkinson's Disease — Patients' Priorities

Data from a retrospective cohort study, also presented at the Congress, investigated the clinical and health economic impact of gastrointestinal disorders in patients with Parkinson's disease:

• Richy F, Gunn A, Makaroff L, Gervasoni C, Helmers S. Disorders in Patients with Parkinson's Disease (PD): A Double-Edged Sword

About Neupro® in Europe

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 occurs. Neupro® is also approved in the European Union for the symptomatic treatment of moderate to severe idiopathic restless legs syndrome in adults.

Neupro® in Europe 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.

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.

Neupro® has been associated with somnolence episodes of sudden sleep onset episodes. Patients treated with dopamine agonists including Neupro®, 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.

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.

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® 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 Neupro® are nausea, vomiting, application site reactions, somnolence, dizziness and headache.

Adverse drug reactions reported in more than 10% of RLS patients treated with Neupro® are nausea, application site reactions, asthenic conditions and headache.

All Neupro® supply should be stored in a refrigerator.

Please refer to the European Summary of Product Characteristics for full prescribing information (Approved 18th August 2010): http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000626/WC500026397.pdf

About Neupro® in the U.S.

Neupro® (rotigotine) 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 Neupro® from the U.S. market after ongoing monitoring revealed that specific batches of Neupro® had deviated from their approved specification. Recently the U.S. Food and Drug Administration (FDA) has recommended that UCB reformulate Neupro® patches and UCB is working on the development of a new formulation. Patients and physicians with questions about the status of Neupro®, or about UCB's Patient Access program for Neupro®, may contact UCB Medical Information at 1-866-822-0068 (option 9).

Important Safety Information – U.S.

Some patients treated with Neupro® 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 Neupro® compared to 0.7% of patients on placebo. Neupro® contains metabisulfite. Neupro® 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 Neupro® 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 Neupro®. Please refer to http://www.neupro.com/documents/Neupro+PI_071207.pdf for full prescribing information.

Neupro® 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.

SOURCE UCB