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Agilect Demonstrates Improvement in Parkinson's Disease Symptoms in Levodopa-Treated Patients
The positive effects seen with once-daily AGILECT® were similar to those seen in patients treated with entacapone, given with each levodopa dose, when compared to placebo. The results of the "LARGO" study (Lasting effect in Adjunct therapy with Rasagiline Given Once daily) will be published in the March 12 issue of The Lancet.
"Motor fluctuations are among the most common disabling complications of levodopa therapy," according to Professor Oliver Rascol, M.D., Ph.D., Department of Clinical Pharmacology, University Hospital, Toulouse, France, and principal investigator of the LARGO trial. "Treatment regimens with other medications, such as a COMT inhibitor or dopamine agonists, have been shown to have some positive effect but also carry a more complicated administration and titration schedule," he said. "The positive results seen in this trial, together with a once-daily dose that does not require titration, means that AGILECT® may offer patients a new treatment option for moderate-to-advanced PD."
The LARGO study was a multicenter, 18-week randomized, placebo-controlled, double-blind, parallel trial implemented at 74 sites in Europe, Israel, and Argentina. The study included 687 PD patients with a clinical diagnosis of idiopathic PD, who were experiencing motor fluctuations despite receiving optimized levodopa therapy with or without stable doses of other additional anti-PD drugs, including dopamine agonists and anticholinergic agents. All patients received optimized levodopa and were randomized to receive AGILECT® (rasagiline tablets) 1mg once-daily, entacapone 200mg with each levodopa dose or placebo.
Patients receiving either AGILECT® or entacapone in addition to levodopa had similar significant reductions from baseline in average total "off" time of 1.20 hours compared with a 0.4 hour reduction in "off" time with placebo. Treatment also resulted in an increase in "on" time, the majority of which was without troublesome dyskinesia (a distortion or impairment of voluntary movement that interferes with daily activities). Additionally, patients treated with once-daily AGILECT® demonstrated significant improvements in PD symptoms based on the Unified Parkinson's Disease Rating Scale (UPDRS) motor sub-scale during "on" and "off" periods. UPDRS ADL (activities of daily living) score at "off" time and Clinical Global Improvement (CGI) score were also significantly improved. The UPDRS is a commonly used research tool that measures a patient's ability to perform simple motor tasks and activities of daily living. There were improvements in tremor, rigidity and bradykinesia (abnormal slowness of movement) in those patients receiving AGILECT® compared to placebo. The results seen with AGILECT® were similar to those seen with entacapone. Only the AGILECT® group demonstrated improvement in gait/instability, UPDRS-freezing, and UPDRS- motor scores in the "practically defined" "off" state.
"The results from this study show that AGILECT® reduces motor fluctuations for patients with PD. Reducing 'off' time and easy to use therapy remain important unmet needs for the treatment of patients with PD," said David Brooks, M.D., DSc., Division of Neuroscience, Hammersmith Hospital, London, England. "These results, along with simple once-daily administration without the need to titrate dosing, are relevant factors in treating patients who may already be receiving complicated treatment regimens."
Patients taking once-daily AGILECT® (rasagiline tablets) experienced adverse events at a rate similar to placebo. The most common events observed with rasagiline versus placebo (at an incidence of 2% or greater in the rasagiline group and greater than or equal to placebo) were postural hypotension (2% versus 0%), peripheral edema (2% versus 1%), depression (3% versus 3%), dizziness (3% versus 2%), dyskinesia (5% versus 4%), hallucinations (2% versus 1%), dry mouth (2% versus 1%) and sleep disorder (3% versus 2%). A lower number of discontinuations due to adverse events were observed in the AGILECT® group (7%) compared to placebo (11%). Overall, the AGILECT® group was comparable with respect to the incidence of dopaminergic adverse events to the placebo and entacapone groups.
The results from the LARGO study are consistent with another pivotal adjunct therapy trial comparing AGILECT® versus placebo published in the February 2005 issue of the Archives of Neurology.
AGILECT® 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 AGILECT® 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 AGILECT® as 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 Americans have PD, which usually initially affects people over the age of 50.
Source: Teva Neuroscience, Inc.