17.10.2005 – 09:04

Boehringer Ingelheim

New Data Confirm Pramipexole Delivers Sustained Efficacy For Patients With Restless Legs Syndrome

Berlin, Germany (ots/PRNewswire)

• For Healthcare Professional Journalists - Not for distribution to US media
• Randomised, Placebo-Controlled Study Shows Discontinuation of Pramipexole Leads to Rapid Worsening of Symptoms -

Two new, randomised, placebo-controlled studies presented this
week at the inaugural conference of the World Association of Sleep
Medicine (WASM), demonstrate that pramipexole - the number one
dopamine agonist prescribed for Parkinson's Disease in the world -
can deliver powerful and sustained efficacy in treating patients
suffering from Restless Legs Syndrome  (RLS)[1,2] ew data from a
randomised, placebo-controlled pramipexole  'withdrawal' study[1],
report that when pramipexole is discontinued in  patients who have
been responding well for six months, this leads to rapid  worsening
of RLS symptoms - confirming for the first time, in a placebo-
controlled trial, that pramipexole can deliver sustained, long-term
symptom  improvement for RLS patients beyond six months. New data
from a 12-weeks,  double-blind, fixed-dose study of 345 patients
further confirm pramipexole  can provide significantly greater
improvement in symptoms of RLS, when  measured by two standard
clinical assessment tools, when compared to  placebo[2].

These new data add to the growing body of clinical evidence that
pramipexole is a well tolerated treatment that can deliver rapid and
significant relief from the symptoms of RLS and bring about
significant improvements in patients' quality of life. Clinical
guidelines recommend dopamine agonists as first-line treatment for
RLS, yet there has been limited data to confirm how long the
treatments continue to relieve symptoms. Restless Legs Syndrome is a
common, but poorly recognized and under-treated neurological disease
that predominantly affects adults.

Proven for the first time: pramipexole delivers sustained efficacy

Although previous clinical evidence has provided a strong
indication that pramipexole has the potential to deliver sustained
efficacy, this evidence has been based on open-label or retrospective
data. Professor Claudia Trenkwalder (Kassel, Germany) et al presented
results from a prospective, placebo-controlled 'randomised
withdrawal' study with pramipexole, which has shown for the first
time that blinded discontinuation of pramipexole in RLS patients who
are responding well, led to rapid worsening of symptoms in most
patients[1]. The study set out to determine how 147 patients with
moderate to severe RLS, who had already been receiving pramipexole
treatment and who had responded well for six months, fared when they
were randomised after six months to receive either a placebo
treatment or to continue to receive pramipexole treatment. The
primary endpoint of the study was assessment of 'Time to Worsening'
of RLS symptoms measured using the International RLS Rating Scale
(IRLS) and the Clinical Global Impressions - Global Improvement
(CGI-I) scale. The results showed: <start_table

BERLIN, Germany, October 17 /PRNewswire/ --

- RLS patients who were randomised to continue treatment with

pramipexole experienced a significantly longer time before their

symptoms worsened than those patients who were randomised on to
placebo

(p<0.0001)

- The proportion of patients that experienced worsening of their

RLS symptoms in the pramipexole group was statistically
significantly

smaller compared to those randomized to receive placebo
(pramipexole

20.5 percent vs. placebo 85.5 percent; p<0.0001)

- After just one week more than 70.0 percent of patients on
placebo

worsened as compared to just 9.0 percent of patients in the
pramipexole

group.

- In addition to the outstanding efficacy on RLS symptoms,

pramipexole also significantly improved the disease-specific
quality of

life score to 90 percent (70 percent for placebo; p<0.0001)

"This is an important study as it represents the first time that
pramipexole has been confirmed in a placebo-controlled RLS trial to
deliver sustained efficacy beyond six months. We have known from
previous studies that pramipexole can provide marked and rapid relief
from RLS symptoms - which is important for patients who want their
treatment to work quickly - but what we could not confirm until now
was whether pramipexole keeps working over a long period of time.
This is good news for people suffering from the distressing symptoms
of Restless Legs Syndrome," commented Professor Trenkwalder.

Reinforcing previously reported efficacy with pramipexole

A second study presented this week at WASM confirms the excellent
short-term efficacy and tolerability of pramipexole in a 12-week,
placebo-controlled, randomised study[2]. This study sought to compare
the efficacy and safety of pramipexole at different doses (0.25mg;
0.5mg and 0.75mg) when compared to placebo. After 12 weeks, patients
who received pramipexole - across all three doses - experienced
significantly greater improvements in symptoms of RLS compared to
placebo. Three hundred and forty five patients were randomised and
339 patients were assessed at the end of 12 weeks for improvement in
RLS symptoms using the IRLS and CGI-I scales.

- IRLS scores at week 12 demonstrated that across all three
      pramipexole doses the IRLS score was significantly improved for
      patients when compared to placebo
    - CGI-I scores also demonstrated that significantly more patients
      who received pramipexole treatment reported themselves as 'much
      improved ' or 'very much improved' at the end of 12 weeks of treatment
      compared to patients treated with placebo.

In both studies pramipexole was generally well tolerated and the
most frequent adverse events were nausea, headache and fatigue.
Pramipexole is currently approved for the treatment of early and
advanced Parkinson's Disease and is being evaluated in clinical
trials as a treatment for reducing the severity and symptoms of RLS.

About pramipexole

Pramipexole, a compound from Boehringer Ingelheim research, was
jointly developed by Boehringer Ingelheim and Pharmacia Corp. (today
Pfizer). Currently, pramipexole is approved for the treatment of the
signs and symptoms of idiopathic Parkinson's Disease, as monotherapy
or in combination with levodopa. The most commonly reported adverse
events in early and late Parkinson's disease in clinical trials were
dizziness, dyskinesia, extrapyramidal syndrome, headache, insomnia,
somnolence, and nausea. Hallucinations and postural (orthostatic)
hypotension may occur. As described in the literature for dopamine
agonists, patients have been reported as showing compulsive behavior.
Patients have reported falling asleep without perceived warning signs
during activities of daily living, including operation of a motor
vehicle, which sometimes resulted in accidents.

Boehringer Ingelheim

The Boehringer Ingelheim group is one of the world's 20 leading
pharmaceutical companies. Headquartered in Ingelheim, Germany, it
operates globally with 144 affiliates in 45 countries and nearly
36,000 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 2004, Boehringer Ingelheim posted net sales of 8.2 billion euro
while spending nearly one fifth of net sales in its largest business
segment Prescription Medicines on research and development.

For more information please visit www.boehringer-ingelheim.com

Notes to Editors

    RLS      Restless Legs Syndrome
             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 adult population aged between
             30 and 79 years [3] and around one-third of sufferers experience
             symptoms more than twice weekly causing moderate to severe
             distress[4]. 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[5,6].
    IRLS     International RLS Rating Scale
    CGI      Clinical Global Impression Scale
             The CGI scale is a clinical-rated instrument that
             consists of four subscales. The CGI-Improvement is
             traditionally used as an endpoint in clinical trials for
             responder analyses while the other subscales are less
             used. The global assessment of overall severity of
             illness, of the overall therapeutic effect and of
             interference of side effects with functioning, provides
             additional information of the overall effectiveness of a
             drug treatment

References

[1]. C. Trenkwalder, K. Stiasny-Kolster and the German
RLS-Pramipexole Study Group. Sustained efficacy of Pramipexole in
Restless Legs Syndrome. WASM 2005; Berlin, Germany; Oral
presentation, Abstract # 057; 16 Oct 2005

[2]. Winkelman J, Sethi K, Kushida C, Becker P, Mahowald M.
Pramipexole  is efficacious and safe in treating RLS patients:
Results of a 12 weeks  placebo controlled, fixed dose study. WASM
2005; Berlin, Germany; Oral  presentation, Abstract # 058; 16 Oct
2005

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

[4]. Hening W et al Impact, diagnosis and treatment of restless
legs syndrome in a primary care population: the REST (RLS
epidemiology, symptoms and treatment) primary care study Sleep Med
2004; 5(3): 237-246

[5]. Allen RP Earley CJ Restless legs syndrome: a review of
clinical and pathophysiologic features J Clin Neurophysiol 2001;
18(2): 128-147

[6]. Earley CJ Clinical practice. Restless legs syndrome New Engl
J Med 2003: 348(21) ; 2103-2109