[MadRiverTurtle]

By Richard Robinson, Contributing Writer, MedPage Today
Published: June 12, 2009
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and


PARIS, June 12 -- The investigational drug safinamide improves "on" time in advanced Parkinson's disease without an increase in troublesome dyskinesias, researchers here said.

Compared with placebo, low-dose safinamide provided 0.5 hours additional "on" time daily, while high-dose safinamide provided 0.7 hours more than placebo (P=0.007), Rupam Borgohain, M.D., of Nizam's Institute of Medical Sciences in Hyderabad, India, reported at the International Congress of Parkinson's Disease and Movement Disorders meeting.

"Safinamide provides an extra half hour of 'on' time to patients who have maxed out their other treatment options," he said.

Patients with advanced Parkinson's disease typically develop motor complications, including a reduction in "on" time (time spent responsive to levodopa). They also develop dyskinesias. Several adjunct medications provide some benefit, but patients are often left with residual "off" time, Dr. Borgohain said.

Safinamide is a novel drug with a dual mechanism: it enhances dopaminergic activity through inhibiting monoamine oxidase B-catalyzed dopamine breakdown, and reduces overactivity of glutamatergic signaling by inhibiting glutamate release.

The latter function is important, Dr. Borgohain said, because it is thought this system may be responsible for development of dyskinesias.

Safinamide has been tested successfully in early Parkinson's disease. To test its efficacy in advanced cases, researchers enrolled 669 patients, average age 60, with disease duration of eight years. They had approximately five hours of daily "off" time despite taking levodopa and one or more adjunct medications.

Patients received placebo or one of two doses of safinamide. They were assessed over 24 weeks by a daily diary of "on" time without dyskinesias or with only minor dyskinesias (the primary efficacy variable).

Other assessments included the Unified Parkinson's Disease Rating Scale (UPDRS), Hamilton Depression Scale, and Dyskinesia Rating Scale.

Total daily "on" time increased by 1.0 hours for patients receiving placebo, by 1.5 hours for those on low-dose safinamide (P=0.0082 versus placebo), and by 1.6 hours for those on high-dose safinamide (P=0.0048 versus placebo).

Neither "on" time with minor dyskinesias, "on" time with troublesome dyskinesias, nor time asleep was significantly different between groups.

Treatment also improved the UPDRS score versus placebo. There was no change in dyskinesias in any group.

Depression improved from safinamide treatment as well, although only in the higher-dose group. Those patients experienced a 1.0-point improvement in the Hamilton score, versus 0.3 points for the placebo-treated patients (P=0.018).

This effect on depression, Dr. Borgohain said, is potentially important for this type of patient. Patients with moderate depression were excluded from the study, he noted, but mild depression is quite common in advanced Parkinson's disease.

The only emergent adverse effect affecting safinamide-treated patients more than placebo-treated patients were dyskinesias, but these were mild and nontroublesome.

There were six deaths during the study -- two in the placebo group, two in the low-dose safinamide group not attributable to treatment, and two in the same group of unknown cause.

Based on the results of this study, Dr. Borgohain said, "Safinamide may be a valuable adjunct to levodopa treatment in more advanced Parkinson's disease patients."

http://www.medpagetoday.com/Neurolog...sDisease/14673