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PROUD is the first study to combine early versus delayed pramipexole treatment with a parallel imaging arm to investigate potential clinical benefits of early treatment of patients with Parkinson’s disease
For medical media, outside the US only
Madrid, Spain, 25 August 2008 – Data presented during the 12th Congress of the European Federation of Neurological Sciences (EFNS), held in Madrid, Spain, from 23 to 26 August, highlight important new ongoing studies with pramipexole in a number of key research areas in Parkinson’s disease (PD): clinical benefits of early treatment initiation, management of PD-related depressive symptoms and a new formulation currently under investigation.
Professor Anthony Schapira, 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 and lead study investigator for PROUD*1,, presented a new approach to investigate the slowing of clinical progression in PD, a key focus of current research due to this important unmet need. Previous pramipexole studies have suggested a potential neuroprotective effect, such as the CALM-PD** study2,3 and in vitro studies. PROUD, however, is the first study to combine measurements of clinical outcomes in a PD patient with measurements of dopamine transporter density of certain brain areas (basal ganglia), through a SPECT imaging arm of the study.1
Commenting on the study so far, Professor Schapira said: “The debate on when and how to treat early Parkinson’s disease patients has been ongoing. Currently, treatment would typically be initiated when symptoms have caused disability. However, providing the medical evidence for a treatment to retard or prevent the progression of PD is a major therapeutic priority and the PROUD study aims to shed more light into this question. Pramipexole was considered an optimal candidate for this study due to evidence suggesting possible benefits to PD patients beyond treating the well-known core symptoms. Based on the unique technique used in this study, PROUD may provide a major breakthrough in our understanding of early PD treatment which would offer hope to the ever increasing number of patients diagnosed with Parkinson’s disease.”
Study results are expected to be available in 2009.
Pramipexole studies pursuing other new avenues of research to meet treatment needs
Further areas of current PD research with pramipexole are the management of PD-related depressive symptoms and ongoing studies to evaluate a new formulation so as to provide physicians and patients using pramipexole with an even broader treatment regimen to better meet differing patient needs and lifestyles.4,5,6
PD-related depressive symptoms
A new pramipexole study conducted in approximately 70 European centres aims to assess management of depressive symptoms in PD patients.7 Emerging data suggest that pramipexole may have a positive effect on depressive symptoms and motivation associated with PD, in addition to effectively controlling the motor symptoms of PD.8-16 The specific receptor profile of pramipexole may be responsible for the possible antidepressant properties of this compound and clinical research is ongoing to determine this aspect of pramipexole’s pharmacological profile in more detail.17,18,19
Professor Paolo Barone, Department of Neurological Sciences, University of Napoli-Federico II, Naples, Italy and lead investigator of both PRODEST4 and the new European study7 said: “Previously, the PRODEST study identified that PD-related depressive symptoms are common, with nearly half of those PD patients receiving anti-depressants continuing to experience depressive symptoms. These symptoms impact significantly on quality of life, both for PD patients and their carers. The new European study aims to provide answers on the role pramipexole may play in managing these commonly experienced PD-related depressive symptoms that are often under-recognised and consequently under-treated.”
Widening choice of pramipexole treatment options
Favourable results of pharmacokinetic phase I studies with a new once daily pramipexole extended release formulation were presented at EFNS and support the development of this new formulation.5,6 Pramipexole is the leading dopamine agonist treatment for PD and these ongoing studies aim to add to the existing treatment regimen with a once daily formulation to go one step further to meeting a broader range of patients’ needs.
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Notes to Editor:
About Parkinson’s disease (PD)
PD 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.20,21 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. The symptoms can vary from patient to patient, but worsen over time.
About PROUD1 (*Assessment of Potential ImPact of PRamipexole On Underlying Disease)
The PROUD study was designed to test the hypothesis that early administration of pramipexole can modify Parkinson’s disease and delay the progression of motor function deterioration in early PD patients. The PROUD study is unique in its design by including a parallel SPECT imaging arm to measure the level of neuron degeneration in the brain.
534 patients with early PD in 98 centres in ten countries were randomised to receive either 1.5mg/day pramipexole or placebo. After six to nine months all patients were given pramipexole for the remainder of the 15 months. The primary endpoint of the study is the change in UPDRS part I, II and III at 15 months compared to baseline values by a blinded rater. UPDRS part I, II and III relate to mentation, behaviour and mood (I), activities of daily living (II) and motor symptoms (III). Secondary endpoints include the change in motor, cognitive and quality of life indices and striatal dopamine transporter (DAT) density by [123I] FP-CIT SPECT in 158 patients between baseline and 15 months.
In the earlier performed CALM-PD trial, 301 patients were randomised to double-blind therapy with pramipexole or levodopa; adjuvant therapy was allowed as rescue if necessary. After four years, initial treatment with pramipexole reduced the risk of developing dyskinesias (involuntary jerking movements, themselves very disabling) by more than 50% versus initial treatment with levodopa.22 These results played a pivotal role in recent guidelines by the American Academy of Neurology which support the advantages of starting treatment with a dopamine agonist.23 While the CALM-PD trial compared the pooled analysis (both mono and combination therapy) after two and four years, this new analysis assessed the effects of mono vs. combination therapy separately in terms of the dyskinesia rate.
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 currently marketed in over 70 countries across the globe.
The most commonly reported adverse reactions in early and late Parkinson’s disease in clinical trials were dizziness, nausea, dyskinesia, hypotension, somnolence, insomnia, hallucination, constipation, headache and fatigue. The most commonly reported adverse reactions in clinical trials for Restless Legs Syndrome were nausea, headache, fatigue and dizziness.
Pramipexole may cause patients 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. It should be noted that impulse control disorders/compulsive behaviours may occur while taking medicines to treat Parkinson`s disease, including pramipexole.
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 135 affiliates in 47 countries and 39,800 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.
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1 Schapira A et al. PROUD: The impact of early vs. delayed treatment with pramipexole on new onset Parkinson’s disease. Poster P1366 presented at the 12th Congress of the European Federation of Neurological Sciences, Madrid, Spain, 24 August 2008
2 Parkinson Study Group. Dopamine transporter brain imaging to assess the effects of pramipexole vs. levodopa on Parkinson’s disease progression. JAMA 2002; 287(13): 1653-1661
3 Jennings DL et al. InSPECT: Investigating the effect of short-term treatment with pramipexole or levodopa on [123I] and SPECT imaging. Abstract 465 at 11th International Congress of Parkinson’s Disease and Movement Disorders, Istanbul 2007
4 Barone P et al. PRODEST – Depressive symptoms in Parkinson’s disease: Pattern across scales. Poster Presentation P-01 / 1.167. 10 December 2007 XVIIth WFN World Congress of Parkinson’s Disease and Related Disorders
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6 Haertter, S et al. A single dose five-way cross-over study to establish an in vitro/in vivo correlation (IVIVC) for oral extended release (ER) formulations with 0.375 mg pramipexole. Poster P1244 presented at the 12th Congress of the European Federation of Neurological Sciences, Madrid, Spain, 24 August 2008
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