No Increased Risk of Treatment-Induced Augmentation in Restless Legs Syndrome (RLS) Demonstrated in Long-Term Placebo-Controlled Study With Mirapexin(R) / Sifrol(R) (Pramipexole)

Ingelheim, Germany (ots/PRNewswire) -

- For Healthcare Media outside the U.S.A.

New data presented today at the 61st Annual Meeting of the
American Academy of Neurology (AAN), in Seattle, U.S.A. show that
augmentation did not significantly differ in RLS patients treated
with Mirapexin(R) /Sifrol(R) (pramipexole*) versus the group
receiving placebo.(1) Augmentation, i.e. the worsening of RLS
symptoms due to pharmacological treatment, has been frequently
observed in patients treated with levodopa, a dopaminergic agent
sometimes used to treat RLS.(2-4) Existing data for pramipexole, a
non-ergot dopamine agonist, suggested that augmentation is less
frequent and less severe than with levodopa,(3) however, until now
there had been no well designed study to compare the frequency of
augmentation under pramipexole versus placebo.

"Although the phenomenon of augmentation in RLS has been widely
recognised by RLS experts, there was a lack of placebo-controlled
studies to differentiate the potential impact of the active drug in
causing symptoms worsening. Because of its already established safety
and efficacy profile in the treatment of RLS, pramipexole was used as
study drug for this trial. The results showed that the risk of
developing augmentation for RLS patients using pramipexole was
comparable to that of those who received a placebo," said Birgit
Högl, MD, assistant professor of neurology, head of the Sleep
Disorders Clinic at the Medical University of Innsbruck, Austria and
lead author of the study. "Diagnosing augmentation is a demanding
task, even for experts familiar with the subject. The results from
this trial, however, are quite reassuring and can support physicians
and patients in their treatment decisions."

Further results from this study presented at AAN reaffirmed
sustained efficacy for pramipexole over a long-term period (26
weeks).(5) Positive response to treatment in this randomised,
placebo-controlled, double-blind clinical trial was significantly
higher for pramipexole compared to placebo measured on the
International RLS Study Group Rating scale (58.6% vs. 42.8%,
P=0.0044), the Clinical Global Impressions-Improvement scale (68.5%
vs. 50.3%, P=0.0010), and the Patient Global Impression scale (62.3%
vs. 44.0%, P=0.0011).(5)

Overall, the data presented at AAN reaffirm the favourable
safety, efficacy and tolerability profile of pramipexole over the
long term for the treatment of Restless Legs Syndrome in patients
with moderate to severe symptoms.

*) See Notes to Editor for further trade names.

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Notes to the Editor:

Study Design

A 26-week randomised, double-blind, placebo-controlled trial to
assess the incidence of augmentation in RLS among recipients of
flexible-dose pramipexole versus placebo. Among the 152 pramipexole-
and 149 placebo- recipients treated for (greater than or equal to) 4
weeks, 47 (30.9%) and 40 (26.8%) qualified for expert-panel review.
Of these, 11.8% of pramipexole recipients and 9.4% of placebo
recipients were classified as augmentation. There was no
statistically significant difference between the two groups in time
to augmentation (P=0.8060).(1)

About Restless Legs Syndrome (RLS)

Restless Legs Syndrome is a neurological disorder characterised
by an uncontrollable urge to move the legs, usually accompanied by
unpleasant and sometimes painful sensations in the legs. Restless
Legs Syndrome affects up to ten percent of the population worldwide
aged between 30 and 79 years(6) and around one-third of sufferers
experience symptoms more than twice weekly causing moderate to severe
distress.(7) 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. Restless Legs Syndrome also has considerable impact
on social activities that require immobility.

More information on Restless Legs Syndrome can be found under
http://www.rlsunderthecovers.com.

About Mirapexin(R)/Sifrol(R) (pramipexole)

Pramipexole (known under the trade names Mirapexin(R), Sifrol(R),
Mirapex(R) and Pexola(R)) is a compound from Boehringer Ingelheim
research first approved in 1997 for the treatment of the signs and
symptoms of idiopathic Parkinson's disease, as monotherapy or in
combination with levodopa. Pramipexole was approved in 2006 for the
symptomatic treatment of moderate to severe idiopathic Restless Legs
Syndrome (RLS). Pramipexole is available in over 70 countries across
the globe.

The most commonly ([greater than or equal to] 5%) reported
adverse drug reactions in patients with Restless Legs Syndrome
treated with pramipexole were nausea, headache, dizziness and
fatigue. The most commonly ([greater than or equal to] 5%) reported
adverse drug reactions in patients with Parkinson's disease treated
with pramipexole were nausea, dyskinesia, hypotension, dizziness,
somnolence, insomnia, constipation, hallucination, headache and
fatigue.

Pramipexole may cause patients, particularly with Parkinson's
disease, 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.

Patients and caregivers should be aware of the fact that abnormal
behaviour (reflecting symptoms of impulse control disorders and
compulsive behaviours) such as binge eating, compulsive shopping,
hypersexuality and pathological gambling have been reported in
patients treated with dopaminergic drugs, including pramipexole. Dose
reduction/tapered discontinuation should be considered.

About Boehringer Ingelheim

The Boehringer Ingelheim group is one of the world's 20 leading
pharmaceutical companies. Headquartered in Ingelheim, Germany, it
operates globally with 138 affiliates in 47 countries and 41,300
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 2008, Boehringer Ingelheim posted net sales of 11.6 billion
euro while spending one fifth of net sales in its largest business
segment Prescription Medicines on research and development.

For more information please visit
http://www.boehringer-ingelheim.com.

References

1. Högl B et al. Similar incidences of augmentation during 26
weeks of double-blind pramipexole treatment for Restless Legs
Syndrome in comparison to placebo. Oral presentation # S07.003
presented on 28 April 2009 at the 61st Annual Meeting of the American
Academy of Neurology, Seattle, U.S.A.

2. Allen R et al. Augmentation of the Restless Legs Syndrome with
carbidopa/levodopa. Sleep 1996; 19(3): 205-213.

3. Trenkwalder C et al. Treatment of Restless Legs Syndrome: an
evidence-based review and implications for clinical practice. Mov Dis
2008; 23(16): 2267-2302.

4. Garcia-Borreguero D et al. Diagnostic standards for
dopaminergic augmentation of Restless Legs Syndrome: report from a
World Association of Sleep Medicine - International Restless Legs
Syndrome Study Group consensus conference at the Max Planck
Institute. Sleep Med 2007; 8(5): 520-530.

5. Högl B et al. Efficacy and safety of pramipexole for Restless
Legs Syndrome: a 26 Week randomised, placebo-controlled clinical
trial in the European Union. Poster # P07.056 presented on 30 April
2009 at the 61st Annual Meeting of the American Academy of Neurology,
Seattle, U.S.A.

6. Phillips B et al. Epidemiology of Restless Legs Symptoms in
adults. Arch Intern Med 2000; 160(14): 2137-2141.

7. Hening W et al. Impact, diagnosis and treatment of Restless
Legs Syndrome in a primary care population: REST (RLS epidemiology,
symptoms and treatment) primary care study. Sleep Med 2004; 5(3):
237-246.

Contact:
Ursula Bardon
Corporate Division Communications
Boehringer Ingelheim GmbH
55216 Ingelheim/Germany
E-mail: press@boehringer-ingelheim.com
Phone: +49-6132-77-2622

ots Originaltext: Boehringer Ingelheim
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Contact:
Contact: Ursula Bardon, Corporate Division Communications, Boehringer
Ingelheim GmbH, 55216 Ingelheim/Germany, E-mail:
press@boehringer-ingelheim.com, Phone: +49-6132-77-2622