[RxPG] Patients with moderate-to-advanced Parkinson's disease (PD) experiencing motor complications who added once-daily AGILECT(R) (rasagiline tablets) to their treatment with optimized levodopa with or without stable doses of other anti-PD medications experienced a significant improvement in their PD symptoms and a significant reduction in "off" time according to the "PRESTO" study published in the February issue of Archives of Neurology.Rasagiline was dosed once-daily and required no titration.
"Results from this study show benefits of rasagiline compared with placebo in moderate-to-advanced levodopa-treated PD patients experiencing motor complications. During disease progression and after months or years of levodopa therapy, these patients commonly experience motor complications, such as unpredictable fluctuations between 'on' and 'off' time," said Ira Shoulson,M.D., professor of neurology at the University of Rochester School of Medicine and principal investigator of the Parkinson Study Group (PSG),the organization that conducted the "PRESTO" trial. "This study showed that rasagiline demonstrated significant benefit in reducing 'off' time, increasing 'on' time, and improving features of Parkinson's disease."
The multicenter, randomized, placebo-controlled, double-blind, parallel
group "Parkinson's Rasagiline: Efficacy and Safety in the Treatment of 'Off'" (PRESTO) study included 472 PD patients who were experiencing at least 2.5 hours of daily "off" time despite optimized treatment with levodopa with or without stable doses of other anti-PD medications at 57 PSG sites in the United States and Canada.
Many patients enrolled were treated, in addition to levodopa, with
dopamine agonists, entacapone and/or anticholinergic medications. Patients received 1 mg or 0.5 mg Rasagiline tablets or placebo once daily.The average reduction in "off" time among patients using Rasagiline was 1.85 hours daily for the 1 mg group and 1.41 hours daily in the 0.5 mg group,while placebo provided a reduction of 0.91 hours daily.
Additionally, rasagiline significantly improved motor function during "on"time (time when medication effectively manages symptoms of PD) and activities of daily living during "off" state based on the Unified Parkinson's Disease Rating Scale (UPDRS). The UPDRS is a research tool commonly used to measure a PD patient's ability to perform motor and mental tasks and activities of daily life.Rasagiline also showed significant improvement on Clinical Global Improvement (CGI) scale scores rated by the examiner. Quality of life,as measured by the PD -- Quality of Life (PDQUALIF) scale, showed a trend toward improvement in patients treated with rasagiline 0.5 mg/day, but not with rasagiline 1 mg/day.
"Rasagiline decreased 'off' time and increased the amount of 'on' time,"
said Matt Stern, M.D., professor of neurology at the University of
Pennsylvania and co-principal investigator for the PRESTO study. "The efficacy and tolerability of rasagiline, as demonstrated in this trial, combined with its once-daily dosing, suggest it may be a promising new treatment for PD."
Patients on rasagiline experienced side effects similar to those of
patients on placebo.Adverse events significantly more common with rasagiline than with placebo were balance difficulty in the 0.5 mg rasagiline group, and weight loss, vomiting, and anorexia in the 1 mg rasagiline group.
Balance difficulty occurred slightly more often in the rasagiline treated patients, but did not appear to be dose-related.Dyskinesias were reported as an adverse event in 10 percent of patients receiving placebo and 18 percent of patients receiving either dosage of rasagiline but did not lead to early terminations.
Rasagiline is a novel, potent, second-generation, selective, irreversible
monoamine oxidase type-B (MAO-B) inhibitor that blocks the breakdown of dopamine, a substance in the brain needed to facilitate movement. A new drug application for rasagiline for the treatment of PD was submitted to the U.S.Food and Drug Administration (FDA) Sept. 5, 2003. Indications are being sought for once-daily rasagiline as a monotherapy in early PD and as an adjunct to levodopa in moderate-to-advanced disease.
Parkinson's disease is a degenerative disorder of the brain. Symptoms can include tremor, stiffness, slowness of movement and impaired balance. An estimated one million North Americans have PD, which usually affects people over the age of 50.
Teva Neuroscience, Inc. and Eisai Inc. will co-promote rasagiline in the United States, once approved by the FDA, as part of a long-term strategic alliance between Teva Pharmaceutical Industries Ltd. and Eisai Co., Ltd. Teva and H. Lundbeck A/S will co-promote the product in Europe, upon expected receipt of Marketing Authorization in Q1 2005.
