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New Studies on Once-Daily Extended Release Pramipexole Presented at American Academy of Neurology Annual Meeting

Posted on: Wednesday, 29 April 2009, 11:41 CDT

Data indicated comparable efficacy and safety for extended release and immediate release formulations of pramipexole

SEATTLE, April 29 /PRNewswire/ -- New findings from two double-blind studies investigating the efficacy, safety and tolerability of pramipexole dihydrochloride tablets in an extended release, once-daily formulation, for the treatment of Parkinson's disease (PD), are being presented today at the American Academy of Neurology (AAN) 61st Annual Meeting in Seattle.

The first study compared the efficacy, safety and tolerability of pramipexole extended release versus the currently available pramipexole immediate release formulation and placebo, in patients with early PD (those who have early symptoms), treated for up to 33 weeks. A statistical analysis conducted at week 18 demonstrated that the pramipexole extended release formulation was superior to placebo and had comparable efficacy to the pramipexole immediate release formulation. Further analysis among the 84 patients who completed the 33 weeks of treatment indicated maintenance of efficacy.

"It is important to provide patients with a treatment regimen that suits their individual needs," stated Robert Hauser, MD, Professor of Neurology, and Director, Parkinson's Disease & Movement Disorders Center at the University of South Florida College of Medicine, and a co-author on both studies. "These data suggest that this potential formulation may be as effective and as safe as the currently available three-times-a-day formulation."

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 extended release formulation, at the same daily dose. 84.5 percent of patients who completed the study were switched successfully, meeting the primary endpoint.

About the Studies

A randomized, double-blind trial comparing pramipexole extended 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 Unified Parkinson's Disease Rating Scale (UPDRS)* II+III score from baseline to week 18 was -5.1 points in the placebo group, -8.1 points in the pramipexole extended 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 extended 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).

*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).

A 9-week, double-blind, randomized, parallel-group study conducted in 156 patients with early PD on stable dose of pramipexole immediate release:

• Patients were randomized overnight to the pramipexole once-daily, extended 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 extended 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 extended release.

In both studies, adverse events observed in patients receiving pramipexole extended release were similar to those seen in previous studies with immediate release pramipexole.

About Parkinson's disease

Parkinson's disease is a progressive neurological disorder that affects nearly one million people in the U.S. It is the second most common chronic neurological disorder in older adults after Alzheimer's. Every nine minutes someone is diagnosed with Parkinson's disease. Symptoms include tremor, muscle rigidity, slowed motion, shuffling gait, and a loss of facial expression. The symptoms vary from individual to individual, but become more severe over time. Although promising research is being conducted, there is currently no cure for Parkinson's disease.

About pramipexole

Pramipexole dihydrochloride tablets, in an immediate release formulation, are indicated in the U.S. for the treatment of the signs and symptoms of idiopathic Parkinson's disease (PD) and for moderate-to-severe primary restless legs syndrome (RLS). Pramipexole is supported by more than a decade of real-world experience in the treatment of Parkinson's disease, with more than 10 million prescriptions written in the U.S. since its launch in 1997.

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. Hallucinations and postural (orthostatic) hypotension may occur. In clinical trials for early PD using immediate release tablets, the most commonly reported side effects of pramipexole that were more frequent than with placebo are nausea (28% vs. 18%), dizziness (25% vs. 24%), somnolence (22% vs. 9%), insomnia (17% vs. 12%), asthenia (14% vs. 12%), and constipation (14% vs. 6%). In clinical trials for advanced PD, the most commonly reported side effects of pramipexole that were more frequent than with placebo are postural hypotension (53% vs. 48%), dyskinesia (47% vs. 31%), extrapyramidal syndrome (28% vs. 26%), insomnia (27% vs. 22%), dizziness (26% vs. 25%), accidental injury (17% vs. 15%), hallucinations (17% vs. 4%), and dream abnormalities (11% vs. 10%).

Patients and caregivers should be informed that impulse control disorders and compulsive behaviors have been reported in patients taking dopamine agonists, including pramipexole.

A once-daily, extended release formulation of pramipexole dihydrochloride tablets is currently under review by the U.S. Food and Drug Administration for the treatment of the signs and symptoms of idiopathic Parkinson's disease (PD).

Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

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 approximately 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 US $17 billion (11.6 billion euro) while spending approximately one-fifth of net sales in its largest business segment, Prescription Medicines, on research and development.

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

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.

Source: PR Newswire

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