New study results support once daily, prolonged release formulation of Mirapexin®/ Sifrol®(pramipexole) for the treatment of Parkinson`s disease

Ingelheim/Germany, 29 April 2009 – First data showing outcomes of two double-blind studies investigating the efficacy, safety and tolerability of Mirapexin® / Sifrol® (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®/Sifrol® (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.)

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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 neurologicaldisorder in older adults after Alzheimer`s. Its worldwide prevalence isestimated to be approximately one to two percent of those over 65 years.4,5,6 Although traditionally PD is associated withmotor 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 sleepdisorders can be significant. Symptoms can vary from patient topatient, but worsen over time.

About Mirapexin®/Sifrol® (pramipexole)
Pramipexole (known under the trade names Mirapexin®, Sifrol®, Mirapex® and Pexola®) 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 (≥ 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.

* See Notes to Editor for further trade names