There is a previous thread about Rotigotine at
viewtopic.php?f=1&t=51315&p=472414&hili ... fe#p472414
If you want to know what Rotigotine is go to -
http://en.wikipedia.org/wiki/Rotigotine
and/or
http://www.health.gov.au/internet/main/ ... tine-mar08
So for those interested here is the latest from Medscape News at this link -
http://www.medscape.com/viewarticle/747 ... ws&spon=26
and the large print version is below -
5-Year Data on Rotigotine Patch for Restless Leg Syndrome
by Kate Johnson
August 4, 2011 — A new study is the first long-term prospective trial of dopamine agonist therapy in restless legs syndrome (RLS).
The study, funded by UCB BioSciences and Schwarz Pharma, manufacturers of transdermal rotigotine, assessed the safety, tolerability, and efficacy of the patch for up to 5 years in patients with RLS.
The findings suggest the rotigotine patch is "generally well tolerated with a good safety profile for up to 5 years," concluded lead study author Wolfgang Oertel, MD, from the University of Marburg, Germany, and colleagues.
However, there were substantial withdrawals among treated patients, with only 43% of patients still being treated at the end of follow-up; more than half of these withdrawals were due to adverse events (AEs).
Study coauthor Diego Garcia-Borreguero, MD, PhD, director of the Sleep Research Institute, in Madrid, Spain, said, "Given the level of disease burden normally seen in RLS and the fact that the study involved monotherapy with a single agent over many years (treatment changes/combination therapies are not rare in RLS), I do not consider the AE-related discontinuation rate as necessarily high."
Dr. Garcia-Borreguero is among 9 of the 11 study authors who have been paid as consultants or advisory board members for UCB BioSciences. Two other authors are employees of the company, with 1 holding stock options.
The results were published online June 27 and appear in the August issue of The Lancet Neurology.
However, in an editorial accompanying the publication, Christopher J. Earley, MD, PhD, associate director of the Sleep Disorders Center and professor of neurology at Johns Hopkins University School of Medicine in Baltimore, Maryland, points out that the benefits reported with 5 years of the daily rotigotine transdermal patch "are not unexpected," but of concern is that only 43% of subjects were able to finish the study.
"The long-term use of these agents is substantially limited by side effects, particularly augmentation or drug tolerance," he writes, adding that the 24-hour dosing "seems excessive" given that most patients' symptoms occur only at night.
"The circadian nature of symptom presentation in restless leg syndrome is one of the defining clinical features of this disease and, as such, should define treatment practice: treatment should be tailored to cover only the symptomatic period," he points out.
Open-Label Extension
Patients were extended into the single-arm, open-label study from a previous 6-week, randomized, double-blind, placebo-controlled trial only if their condition worsened within 7 days of no therapy to more than 50% of their baseline International Restless Legs Syndrome (IRLS) score.
A total of 295 patients aged 18 to 75 years were enrolled from 33 centers in Austria, Germany, and Spain between July 31, 2003, and April 15, 2009.
All patients were treated with the once-daily rotigotine transdermal patch, with the dose titrated in weekly increments from 0.5 mg/24 hours to 4 mg/24 hours and then followed up for up to 5 years of maintenance treatment at the optimum dose. The mean dose at the end of the study was 3.09 mg/24 hours.
Although 126 patients (43%) completed the 5 years of follow-up, 169 (57%) discontinued treatment — 53% of discontinuations (n = 89) because of adverse events, 18% (n = 31) for lack of efficacy, and the remaining 29% (n = 49) for other reasons (primarily protocol deviation, unsatisfactory compliance, or withdrawal of consent).
Of those who completed the study, 39% were classified as symptom free according to the IRLS, with the mean score for these patients decreasing from 27.8 at baseline to 9.0 at the end of the study.
Mean scores on the RLS-6 showed the greatest absolute changes from baseline in the categories of sleep satisfaction, severity of symptoms falling asleep, and severity of symptoms during the night — decreasing by 4.5, 4.3, and 5.1 points, respectively.
Scores for daytime symptoms decreased by a mean of 2.9 points while resting and 1.3 points while active, with a mean decrease of 2.6 points in daytime tiredness and sleepiness.
Overall, 93% of subjects (n = 273) had one or more treatment-emergent AE, and 33% of subjects (n = 97) had a severe AE. The most frequently reported treatment-emergent AE was application site reaction, reported by 172 subjects (58%). Overall, application site reactions resulted in discontinuation in 19% of patients.
Clinically significant drug-induced augmentation of symptoms was recorded in 13% of patients.
Long-Term Use 'Substantially Limited'
"The findings raise important questions as to what we are treating with dopamine agonists, what we are not treating, and how we induce the pharmaceutical industry to think differently about restless legs syndrome and, thus, push development towards truly new and improved treatments," Dr. Earley writes in his editorial, musing on "did we really need another dopaminergic drug" for RLS.
In the end, he concludes that the study findings suggest long-term use of dopamine agonists are "substantially limited" by side effects, augmentation, and drug tolerance in particular.
However, Dr. Garcia-Borreguero argued that the study actually suggests the opposite.
"The 5-year incidence of augmentation with rotigotine was consistent with that observed in a previous 6-month, placebo-controlled study on rotigotine and is far lower than the incidences of augmentation observed in shorter studies with other dopamine agonists," he told Medscape Medical News. "Augmentation led to discontinuation in only 4% of patients. The incidence of augmentation with rotigotine may be even lower when low doses are used."
In addition, he pointed out that "the most common adverse reactions were application site reactions (58% of total), and in most cases these were mild to moderate and also transient. Other dopaminergic side effects (nausea, etc) were lower than typically reported for this class of agents in RLS."
In response to the Dr. Earley's comment that treatment should be tailored to cover only the symptomatic nocturnal period, Dr. Garcia-Borreguero pointed out that daytime symptoms were prominent in the study cohort.
"In contrast to most trials of intermediate-acting oral dopamine agonists, our study did not use the presence of daytime symptoms occurring before 6 PM as an exclusion criterion. Daytime symptoms while at rest were present in 95.5% of patients entering the double-blind phase," he said.
"The available literature supports the view that a significant part of the RLS population suffers from RLS symptoms during the day. Thus, in a large multinational survey 61% of patients reported difficulties in sitting still or relaxing during the day, and 57% reported that their daytime activities were disturbed by the presence of symptoms. Similarly, in other studies performed in the general population, clinically significant daytime symptoms are described in up to 40% of RLS patients."
"It is particularly important to remind the public that this is by far the longest prospective study ever performed on RLS," he continued. "In comparison, other drugs (dopaminergic or other) have been investigated prospectively for RLS during periods of at most 1 year. Thus, when evaluating the long-term tolerability of any single agent in RLS, we must keep in mind that we do not have other treatment or naturalistic studies to compare with."
Nine of the 11 study authors have either worked as paid consultants or scientific advisory board members for UCB BioSciences or their institutions have received fees for these services. The 2 other authors are employees of UCB BioSciences, one of them owning stock. In collaboration with the study investigators, the study sponsor performed the statistical analysis and contributed to the study design, data collection, data interpretation, and reporting of results. The study authors had full access to all of the data in the study. Dr. Earley served on a safety monitoring board for a Merck-sponsored phase 3 trial of an insomnia drug.
Lancet Neurol. 2011;10:710-720, 675-677. Abstract Editorial
Medscape Medical News © 2011 WebMD, LLC
cheers
Mars
