Ingelheim/Germany -- New data presented today at the Movement Disorder Society’s 13th International Congress of Parkinson’s Disease and Movement Disorders (MDS) further confirms high therapeutic benefit of Mirapexin®/Sifrol® (pramipexole) once-daily, extended release formulation (also referred to as prolonged release formulation).

The trial, performed in patients with advanced Parkinson’s disease (PD), showed results comparable to pramipexole’s already long-established immediate release formulation.1 This study supports data from a previous trial that demonstrated the efficacy, safety and tolerability of the once daily formulation in the treatment of early PD at 18 weeks,2 and non-inferiority between pramipexole extended release and pramipexole immediate release at 33 weeks as presented for the first time today at the MDS.4

The randomised, placebo-controlled trial assessed the efficacy and safety of a once-daily, extended release formulation of pramipexole - administered as adjunctive therapy in advanced PD - compared to its immediate formulation when administered under the same therapeutic conditions. Both the primary and the key secondary endpoints were met in the study as measured by the change from baseline in UPDRS II+III and percentage of off-time during waking hours.

"These most recent study data show that the pramipexole once-daily, extended release formulation is effective not only in early but also in the more advanced stages of Parkinson’s disease. The improvement seen in ‘off-time’ (known as a period of dramatically reduced motor functioning at the end of the dosing interval), as well as the convenience of a once-daily formulation, is a benefit both patients and physicians will welcome. Having a once-daily pill is especially important for those in an advanced stage of the disease when the need for multiple medications often increases,” commented Professor Anthony Schapira, lead investigator of the study, Chairman of the University Department of Clinical Neurosciences, Institute of Neurology, Queen Square, UCL and Professor of Neurology at the National Hospital and Royal Free Hospital, London, UK.

(Note: Mirapexin®/Sifrol® (pramipexole) is currently registered as immediate release formulation only.)

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Summary of early PD and advanced PD pramipexole trial results

A randomised, placebo-controlled, double-blind trial comparing pramipexole extended.release (ER) and immediate release (IR) formulations versus placebo, as adjunctive therapy, after 18 weeks of treatment, in patients with advanced PD: o A total of 507 patients were included in the efficacy analyses at week 18.

• In these patients, the adjusted mean change in UPDRS* II+III score from baseline to week 18 was -6.1 points for placebo, -11.0 points for prolonged release (p=0.0001 vs. placebo) and -12.8 points for immediate release (p<0.0001 vs. placebo).
• The adjusted mean change in percentage off-time was -8.8 points for placebo, -13.3 points for prolonged release (corresponding to an improvement of -2.1 hours from baseline; p=0.0122 vs. placebo) and -15.9 for immediate release (corresponding to an improvement of -2.5 hours from baseline p<0.0001 vs. placebo).
• Adverse event rates were similar for pramipexole ER (54.9%) compared to placebo (55.6%) and numerically lower than pramipexole IR (64.0%).

A randomised, placebo-controlled trial double-blind trial comparing pramipexole extended release (ER) and immediate release (IR) 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 analysis testing for superiority of pramipexole extended release versus placebo.
• 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 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 first 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 versus –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).3
• Non-inferiority between pramipexole extended release and pramipexole immediate release was assessed at week 33. The adjusted mean change in the UPDRS II+III score from baseline to week 33 were –8.6 points in the pramipexole extended release group (n = 213) and –8.8 points in the pramipexole immediate-release group (n = 223), a between-group difference of –0.2 points, 95% CI=[–2.2; 1.7]. The lower bound of the 95% CI (–2.2 points) was higher than the pre-defined non-inferiority margin of –3 points, demonstrating non-inferiority between pramipexole extended release and pramipexole immediate release at week 33.4

*The 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.5-7 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®/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.

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

Related links: Further information on Parkinson’s disease and pramipexole

References:
1 Schapira, A et al. Efficacy and safety of pramipexole extended-release for advanced Parkinson’s disease. Poster We-199, presented at13th International Congress of Parkinson’s Disease and Movement Disorders (MDS), Paris, France, 09 June 2009)
2 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.
3 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.
4 Poewe, W et al. Pramipexole Extended-Release is Effective in Early Parkinson’s Disease. Poster We-185, presented at13th International Congress of Parkinson’s Disease and Movement Disorders (MDS), Paris, France, 10 June 2009
5 Nussbaum R et al. Alzheimer’s disease and Parkinson’s disease. N Engl J Med 2003;348:1356-64.
6 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.
7 Parkinson Study Group, Holloway RG et al. Pramipexole vs levodopa as initial treatment for Parkinson disease. Arch Neurol 2004; 61(7): 1044-1053.

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