Results from three different clinical studies of Sifrol(R) / Mirapexin(R) (pramipexole), presented at the 20th annual meeting of the Associated Professional Sleep Societies (APSS), demonstrate significant improvement of a broad range of Restless Legs Syndrome (RLS) symptoms - throughout both the night and day. Study results included rapid and sustained relief from RLS symptoms, improved sleep quality, and overall enhanced quality of life.1,2,3,4,5

These results reflect the European Commission's recent approval of Sifrol(R)/ Mirapexin(R), for the treatment of moderate to severe Restless Legs Syndrome - the first treatment of its kind to be approved throughout the European Union for this indication.

"This data supports the efficacy and safety of Sifrol(R) / Mirapexin(R) as a treatment for RLS to help manage patients' symptoms," said lead investigator of one study, John W. Winkelman, MD, PhD, Medical Director, Sleep Health Center, Brigham and Women's Hospital, USA.

"Research findings and clinical experience have shown that RLS is typically very responsive to treatment, particularly with dopaminergic agents," he continued. "In our study, it was noteworthy that patients' RLS symptoms, as well as satisfaction with their sleep, were significantly improved when taking Sifrol(R) /Mirapexin(R). However, it is a common misconception that people with RLS suffer only at night whilst asleep. The reality is that patients often experience a multitude of night and day-time symptoms which impact on their quality of life. Treatment options like Sifrol(R)/Mirapexin(R) offer hope to the millions of RLS sufferers worldwide."

The symptoms of RLS include difficulty falling and staying asleep, which is the most common reason patients present to a physician yet the condition is still greatly underdiagnosed.

Efficacy and Tolerability of pramipexole

The data presented at this congress describe the favourable efficacy and tolerability profile of pramipexole in RLS treatment.

The patients global impression of improvement (PGI) scale* was utilised to assess the early benefit of low-dose pramipexole. After one week, 42.5 percent of the studied population rated themselves as "much" or "very much" better in the pramipexole group compared with only 14.1 percent of patients in the placebo group. This improvement in patient ratings was maintained throughout the 12-week treatment phase. The therapeutic effects of low-dose pramipexole were apparent already at the 0.125-mg dose, allowing patients to achieve a rapid onset of effectiveness with minimal side effects.3

Moreover, pramipexole significantly improved RLS symptoms while getting to sleep, during the night, and during the day, and it substantially improved satisfaction with sleep in patients with moderate to severe RLS.1

A special withdrawal design of one of the studies allowed assessment of the effect of removing pramipexole therapy on sleep satisfaction in pramipexole responders from a previous treatment period. Six months of treatment with pramipexole led to a substantial improvement in RLS symptoms and sleep disturbances. Continuation of pramipexole therapy maintained the treatment benefits up to nine months, while withdrawal of the effective pramipexole treatment led to a rapid and substantial worsening of RLS symptoms and sleep outcomes.2

Improvement of RLS-related Quality of Life

Patients with Restless Legs Syndrome, experience reduced Quality of Life (QoL) relative to the general population, and the impact of RLS is comparable to that of other major diseases when evaluated with the 36-item short-form health survey (SF-36) QoL scale.**6

Patients maintained on pramipexole up to nine months experienced significant and sustained improvements in QoL, whereas patients withdrawn from the effective treatment after six months experienced significant worsening of their condition.4

Reduction in Daytime Tiredness

One common adverse effect of RLS is daytime tiredness. The results of a multi-national study conducted in five European countries, involving 345 patients showed that pramipexole was effective in the treatment of moderate to severe RLS both after six weeks and was maintained up to 52 weeks of therapy. In addition to the benefits seen on the IRLS scale, Pramipexole significantly reduced daytime tiredness compared with placebo.5

About Restless Legs Syndrome (RLS)

RLS is a neurological disorder characterised by an uncontrollable urge to move the legs, usually accompanied by unpleasant and sometimes painful sensations in the legs. RLS affects up to ten percent of the population worldwide aged between 30 and 79 years7 and around one-third of sufferers experience symptoms more than twice weekly causing moderate to severe distress.8 The motor-restlessness worsens during the evening and night causing difficulty initiating and maintaining sleep. The sleep disruption can lead to excessive daytime sleepiness and compromise work performance. RLS also has considerable impact on social activities that require immobility.

About pramipexole

Pramipexole (known in Europe under the trade names Sifrol(R) and Mirapexin(R) and in the U.S.A. as Mirapex(R) ), is a compound from Boehringer Ingelheim research first licensed in 1997 for the treatment of the signs and symptoms of idiopathic Parkinson`s Disease, as monotherapy or in combination with levodopa. In April 2006, Sifrol(R)/ Mirapexin(R) was approved for the treatment of moderate to severe Restless Legs Syndrome throughout the European Union.

The most commonly reported adverse reactions in clinical trials in early and late Parkinson's disease were dizziness, involuntary movement, postural hypotension, constipation, hallucinations, headache, difficulty falling asleep, sleepiness, nausea and fatigue. The most commonly reported adverse reactions in clinical trials for Restless Legs Syndrome were nausea, headache, and tiredness.

Pramipexole may cause patients to fall asleep without any warning, even while doing normal daily activities such as driving. When taking pramipexole hallucinations may occur and sometimes patients may feel dizzy, sweaty or nauseated upon standing up. It should be noted that impulse control disorders/compulsive behaviours can occur while taking medicines to treat Parkinson`s disease, including pramipexole.

Boehringer Ingelheim

The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 143 affiliates in 47 countries and almost 37,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2005, Boehringer Ingelheim posted net sales of 9.5 billion euro while spending almost one fifth of net sales in its largest business segment Prescription Medicines on research and development.

*The Patient Global Impression Scale (PGI) is a seven point self rating scale in which patients rate themselves from "very much better" (score =1) to "very much worse" (score = 7).

It is similar to the Clinical Global Impressions Scale (CGI) scale, which is an assessment completed by a physician.

**SF-36(R)

The SF-36 is a multi-purpose, short-form health survey with 36 questions, used as a measure of generic health status in the general population. From the 36 items, 8 health profiles are derived from summarised scores.

The SF-36 has been translated and adapted in 29 countries.

References:

1 Winkelman JW, Sethi KD, Kushida CA, Becker PM, Koester J, Cappola JJ, Reess J. Effects of Pramipexole on Subjective Measures of Sleep Quality and Symptom Severity in Patients with Restless Legs Syndrome. APSS 2006; Salt Lake City, UT; Poster presentation #P137, To be presented, June 21, 2006.

2 Trenkwalder C, Stiansny-Kolster K, Kupsch A, Ortel WH, Koester J, Rees J, Rebound of Sleep Disturbances After Rapid Discontinuation of Pramipexole in Patients with Restless Legs Syndrome. Movement Disorders. Published online 5 Jun 2006. Accessed via http://www3.interscience.wiley.com/cgi-bin/abstract/112650134/ABSTRACT. 8 Jun 2006.

3 Corbin AE, Sethi KD, Kushida CA, Becker PM, Koester J, Cappola JJ, Reess J, Winkelman JW JW, Pramipexole Treatment Rapidly Improves Patient Ratings of Restless Legs Syndrome Symptoms; APSS 2006; Salt Lake City, UT; Poster presentation, #P140; To be presented, June 21, 2006.

4 Hoegl B, Stiasny-Kolster K, Kupsch A, Oertel W, Koester J, Reess, J. Pramipexole Produces Sustained Improvements in Quality of Life in Patients With Restless Legs Syndrome. APSS 2006; Salt Lake City, UT; Poster presentation, # P137; To be presented, June 21, 2006.

5 Oertel W, Stiasny-Kolster K, Bergtholdt B, Hallstrom Y, Albo J, Leissner L, Schindler T, Koester J, Reess J. Pramipexole Does Not Cause Daytime Sleepiness In Patients Treated For Restless Legs Syndrome. APSS 2006; Salt Lake City, UT; Poster presentation, #P139; To be presented, June 21, 2006.

6 L Abetz et al. Evaluating the quality of life of patients with restless legs syndrome. Clinical Therapeutics 2004 26: 925-935.

7 Phillips B et al Epidemiology of restless legs symptoms in adults Arch Intern Med 2000; 160(14): 2137-2141.

8 Allen RP, Walters AS, Montplaisir J, Hening W, Myers A, Bell TJ, et al. Restless legs syndrome prevalence and impact: REST general population study. Arch Intern Med 2005; 165 :1286 -1292.

http://www.boehringer-ingelheim.com