New Study Results Support Once Daily, Prolonged Release Formulation of Mirapexin(R)/Sifrol(R) (Pramipexole) for the Treatment of Parkinson's Disease

Ingelheim, Germany (ots/PRNewswire) -

- Data for the Once Daily Mirapexin(R)/Sifrol(R) (Pramipexole)
Formulation Under Development Show Efficacy, Safety and Tolerability
Outcomes Comparable to the Current Immediate Release Formulation for
the Treatment of Parkinson's Disease

For non-US Healthcare Media

First data showing outcomes of two double-blind studies
investigating the efficacy, safety and tolerability of
Mirapexin(R)/Sifrol(R) (pramipexole(*)) in a prolonged release, once
daily formulation, for the treatment of Parkinson's disease (PD),
were presented at the American Academy of Neurology Annual Meeting
(AAN) in Seattle, U.S.A.

The first study compared the efficacy, safety and tolerability of
pramipexole prolonged release versus pramipexole immediate release
and placebo, in patients with early PD treated for up to 33 weeks. A
confirmatory statistical analysis conducted at week 18 demonstrated
that the pramipexole prolonged release formulation was superior to
placebo and had a comparable efficacy to the pramipexole immediate
release formulation, at the same daily dosage. A descriptive
statistical analysis showed maintenance of efficacy after 33 weeks of
treatment compared to 18 weeks of treatment in both pramipexole
groups, while placebo patients worsened from week 18 to week 33.(1,2)

Commenting on the study, Werner Poewe, MD, Professor of Neurology
and Director of the Department of Neurology, University Hospital
Innsbruck, Austria said: "Every patient with Parkinson's disease will
have a different range of symptoms or requirements. Bearing this in
mind, it is important to provide patients with a treatment regimen
that not only suits their individual needs, but also gives
reassurance to physicians that new formulations are as good as their
current formulations when it comes to efficacy, safety and
tolerability."

The second study, also conducted in patients with early PD,
assessed the efficacy and safety of an overnight switch from
pramipexole immediate release to a pramipexole prolonged release
formulation, at the same daily dose. The study showed that 84.5
percent of patients were switched successfully from pramipexole
immediate release to pramipexole prolonged release (a successful
switch was defined as no worsening by more than 15 percent from
baseline in the Unified Parkinson's Disease Rating Scale (UPDRS)
II+III score and no drug-related adverse events leading to
discontinuation).(3)

Results from trials in patients with advanced PD will be
presented later this year and are expected to further support a
Mirapexin(R)/Sifrol(R) (pramipexole) once daily, prolonged release
formulation. The new formulation for pramipexole is currently under
evaluation by the U.S. and European regulatory agencies.

(Note: Pramipexole is currently registered as immediate release
formulation only.)

Please be advised

This release is from Boehringer Ingelheim Corporate Headquarters
in Germany. Please be aware that there may be national differences
between countries regarding specific medical information, including
licensed uses. Please take account of this when referring to the
information provided in this document. This press release is not
intended for distribution within the U.S.A.

Notes to Editor:

About the pramipexole prolonged release, once daily formulation
studies

- A randomised, double-blind trial comparing pramipexole
prolonged release and immediate release formulations versus placebo
after 18 weeks and 33 weeks of treatment, in patients with early PD:

A total of 253 patients were included in the 18-week confirmatory
analysis. In these patients, the adjusted mean change in the UPDRS
II+III score from baseline to week 18 was -5.1 points in the placebo
group, -8.1 points in the pramipexole prolonged release group
(p=0.0282 vs. placebo), and -8.4 points in pramipexole immediate
release group (p=0.0153 vs. placebo). A sub-group of 84 patients had
completed 33 weeks of treatment at the interim analysis cut-off and
were included in the descriptive analysis of maintenance of efficacy.
The UPDRS II+III score was almost unchanged from week 18 to week 33
in both pramipexole groups, while a worsening was observed in placebo
patients. In the pramipexole prolonged release group, the adjusted
mean change from baseline in the UPDRS II+III score was -11.5 points
at week 33 and -11.8 points at week 18, a difference of +0.3 point
(or 2.5 percent). For the pramipexole immediate release group, both
changes (week 33 and week 18) were -11.9 points, a difference of 0
percent. For the placebo group, the mean change was -2.7 points at
week 33 versus -4.2 points at week 18, a worsening of +1.5 points (or
35.7 percent).(1,2)

- A 9-week, double-blind, randomised, parallel-group study
conducted in 156 patients with early PD on stable dose of pramipexole
immediate release: Patients were randomised overnight to the
pramipexole once daily, prolonged release or to the pramipexole
immediate release formulation (2:1 ratio). Primary efficacy endpoint
was the proportion of patients successfully switched (no worsening of
UPDRS II+III >15 percent from baseline and no drug-related adverse
event leading to withdrawal). 95.5 percent of patients completed the
trial, of which 84.5 percent were successfully switched (with or
without dose adaptation) to the once daily formulation. Mean
pramipexole prolonged release dosage increased from 2.63 to 2.75mg/d
(a ratio of 1:1.05) and mean pramipexole immediate release dosage
from 2.74 to 2.83mg/d (a ratio of 1:1.03); these data support a 1:1
switch from pramipexole immediate release to pramipexole prolonged
release.(3)

Unified Parkinson's Disease Rating Scale (UPDRS)

The Unified Parkinson's Disease Rating Scale (UPDRS) is a
comprehensive tool, which was developed to follow the longitudinal
course of PD-related disability and impairment. The UPDRS II+III
score was used as the primary efficacy endpoint in both trials. UPDRS
Part II relates to activities of daily living and UPDRS Part III
relates to motor symptoms. The UPDRS II+III score ranges from 0 (no
disability) to 160 (worst disability).

About Parkinson's disease (PD)

Parkinson's disease is the second most common chronic
neurological disorder in older adults after Alzheimer's. Its
worldwide prevalence is estimated to be approximately one to two
percent of those over 65 years.(4,5,6) Although traditionally PD is
associated with motor symptoms (such as tremor, rigidity, slowed
motion, imbalance, shuffling gait, loss of facial expression), the
non-motor symptoms, including depressive symptoms, pain, cognitive
impairment and sleep disorders can be significant. Symptoms can vary
from patient to patient, but worsen over time.

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 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.

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.

Related links:

Further information on Parkinson's disease and pramipexole can be
found at http://www.PDKnowledgeGuide.com.

References

1. Hauser R et al. Double-blind evaluation of pramipexole
extended-release (ER) in early Parkinson's disease. Abstract S43.003
presented on 30 April 2009 at 61st Annual Meeting, Seattle, USA.

2. Salin L et al. Double-blind evaluation of maintenance of
efficacy of pramipexole extended-release in early Parkinson's
disease. Abstract P06.150 presented on 29 April 2009 at AAN 61st
Annual Meeting, Seattle, USA.

3. Rascol O et al. Overnight switching from immediate- to
extended-release pramipexole in early Parkinson's disease. Abstract
P06.152 presented on 29 April 2009 at AAN 61st Annual Meeting,
Seattle, USA, 30 April - 02 May 2009.

4. Nussbaum R et al. Alzheimer's disease and Parkinson's disease.
N Engl J Med 2003;348:1356-64.

5. de Rijk MC et al. Prevalence of Parkinsonism and Parkinson's
disease in Europe: the EUROPARKINSON Collaborative Study. European
Community Concerted Action on the Epidemiology of Parkinson's
disease. J Neurol Neurosurg Psychiatry. 1997;62:10-5.

6. Parkinson Study Group, Holloway RG et al. Pramipexole vs
levodopa as initial treatment for Parkinson disease. Arch Neurol
2004; 61(7): 1044-1053.

(*) See Notes to Editor for further trade names

Contact:
Ursula Bardon
Corporate Division Communications
Boehringer Ingelheim GmbH
55216 Ingelheim/Germany
Phone: +49-6132-77 2622
Fax: +49-6132-72 2622
E-mail: press@boehringer-ingelheim.com

ots Originaltext: Boehringer Ingelheim
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Contact:
Contact: Ursula Bardon, Corporate Division Communications, Boehringer
Ingelheim GmbH, 55216 Ingelheim/Germany, Phone: +49-6132-77 2622,
Fax: +49-6132-72 2622, E-mail: press@boehringer-ingelheim.com