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Rasagiline Slows Functional Decline in Patients With Parkinson's: Presented 
at ANA
By Andrew N. Wilner, MD

SALT LAKE CITY, Utah -- September 24, 2008 -- Early treatment with 
rasagiline 1 mg slows functional decline in patients with Parkinson's 
disease, according to research presented here at the American Neurological 
Association (ANA) 133rd Annual Meeting.

The ADAGIO delayed-start trial was the first prospectively-designed clinical 
trial to test the potential of rasagiline to delay the progression of 
Parkinson's disease.

Rasagiline is a selective, irreversible, second-generation monoamine oxidase 
B inhibitor and may possess neuroprotective properties, possibly due to its 
propargyl moiety, said Warren Olanow, MD, Mount Sinai School of Medicine, 
New York, New York.

"Neuroprotection is the holy grail of treatment for Parkinson's disease," 
Dr. Olanow observed in a presentation on September 23. "Symptoms such as 
falling, freezing, and dementia are nondopaminergic and a major cause of 
disability in the later stages of Parkinson's disease. We need 
neuroprotective therapies to address these symptoms."

For their study, Dr. Olanow and colleagues enrolled 1,176 patients with 
early, previously untreated Parkinson's disease. Diagnosis was based on the 
presence of resting tremor, bradykinesia, or rigidity. The study used a 
delayed-start design with 4 treatment arms: rasagiline 1 or 2 mg/day for 72 
weeks (early start) or placebo for 36 weeks followed by rasagiline 1 or 2 
mg/day for 36 weeks (delayed start).

At the end of the first, double-blind, placebo-controlled, 36-week phase, if 
there were a difference in outcome as measured by the Total Unified 
Parkinson's Disease Rating Scale (UPDRS), the placebo group would be 
switched to rasagiline.

Results at the end of 36 weeks show a significant benefit with rasagiline 1 
mg compared with placebo in the UPDRS score as measured by the slope of 
rasagiline minus the slope of placebo = -0.05 (P = .0133). At that time, the 
placebo patients were switched to rasagiline 1 mg and both groups were 
followed for another 36 weeks.

At the end of 72 weeks, the early rasagiline group maintained its 
superiority. Further, there was noninferiority of the slopes of the 2 
active-treatment groups, which suggests that the group that began treatment 
late could not catch up to the benefits achieved in UPDRS by the early 
treated group.

With rasagiline 2 mg, there was significant benefit at the end of 36 weeks 
compared to placebo. However, at the end of an additional 36 weeks, both 
groups had similar efficacy, suggesting there was no advantage of starting 
rasagiline 2 mg early. Dr. Olanow acknowledged that there was not a ready 
explanation why the 1 mg dose but not the 2 mg dose demonstrated persistent 
superiority to the late-start treatment.

Dr. Olanow concluded, "Early treatment with rasagiline 1 mg provides a 
benefit that cannot be achieved with later introduction of the same drug. 
This may be evidence of neuroprotection or preservation or enhancement of 
supportive, compensatory mechanisms."

[Presentation title: Early Rasagiline Treatment Slows UPDRS Decline in the 
ADAGIO Delayed Start Study. Abstract WIP-11]

Rayilyn Brown
Director AZNPF
Arizona Chapter National Parkinson Foundation
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