BOSTON – The addition of safinamide to ongoing dopamine agonist monotherapy lessened motor and cognitive symptoms in a group of patients with Parkinson's disease, according to the results of a randomized, placebo-controlled, multinational Phase III trial.
The higher dose tested offered no advantage over the lower dose, according to the presentation made by Dr. Fabrizio Stocchi at the 59th annual meeting of the American Academy of Neurology.
“Dopamine agonists tend to lose their effects [with extended use],” says Dr. Stocchi, a professor of neurology at the Institute of Neurology IRCCS San Raffaele Pisana in Rome. “We asked whether another compound can expand dopamine agonist monotherapy.”
Safinamide is a selective and reversible inhibitor of MAO-B. It inhibits dopamine reuptake and glutamate release, and does not potentiate the effects of tyramine.
A total of 270 patients with early Parkinson's disease (PD) maintained for at least 4 weeks on dopamine agonist monotherapy were randomized into three groups receiving either supplemental safinamide in low dose (50–100 mg/day), high dose (150–200 mg/day), or placebo.
The results showed that after 24 weeks of treatment with low-dose safinamide plus dopamine agonist, the Unified Parkinson's Disease Rating Scale (UPDRS) Part III motor score was significantly improved over the effect of dopamine monotherapy (mean change from baseline: low dose vs. control: −6.0 plus or minus 7.2 vs. −3.6 plus or minus 7.1; P=.0125).
Scores for the high-dose safinamide group (−3.9 plus or minus 6.0) were not significantly better than those of the controls. The number of responders (patients showing a 30% improvement or more) on the UPDRS III also increased with the low-dose combination therapy.
Safinamide/dopamine agonist combination therapy had other benefits.
Significant improvements with low-dose safinamide were also noted on the UPDRS Part II Activities of Daily Living Score, the EuroQoL, and the Clinical Global Impression-C. No clinically significant side effects were reported with either dose of safinamide.
Low-dose safinamide-treated patients also performed better on the Cogtest battery, designed to evaluate cognitive domains known to be impaired in Parkinson's patients.
Improved scores were noted in several cognitive domains, including spatial working memory, strategic target detection, and auditory number sequencing.
Dr. Stocchi is involved in a 1-year extension phase of the study. A Phase III pivotal study of safinamide as an add-on to levodopa in patients with mid- to late-stage Parkinson's is underway.