Safinamide improves "on time" and other symptoms and reduces dyskinesias in patients with Parkinson's disease.
Safinamide improves symptoms and reduces dyskinesias for at least 24 months in Parkinson's disease patients who experience disability because of these movements, according to a study presented at the 63rd Annual Meeting of the American Academy of Neurology.
Safinamide dosed at 100 mg/day reduced dyskinesias by 24% in patients with the worst initial dyskinesias, when compared to placebo. Patients in all groups gained approximately 50 minutes of additional “on” time from safinamide treatment. “On” time is the time the patient is experiencing symptomatic benefit of drug treatment.
Safinamide is an alpha-aminoamide with both dopaminergic and non-dopaminergic actions, explained lead investigator Ravi Anand, MD, of Newron Pharmaceuticals, Switzerland. Its non-dopaminergic actions include MAO-B inhibition (another mechanism of symptomatic benefit exploited in PD), blockade of sodium channels, and inhibition of glutamate release.
A prior six-month placebo-controlled study of safinamide in PD showed its ability to improve “on” time without exacerbating dyskinesias. Dyskinesias are aberrant movements that develop in advanced PD in response to levodopa therapy, and represent a major challenge to management.
Five hundred forty-four patients from the six-month study enrolled in the current study, an 18-month double-blind, placebo-controlled extension study. Patients were randomized to safinamide at 50 mg or 100 mg per day, or to placebo. Patients were allowed other anti-PD medications, including levodopa but excluding other MAO-B inhibitors.
Four hundred forty (81%) patients completed the study, with approximately equal numbers in each arm.
The primary outcome measure was change from baseline in the Dyskinesia Rating Scale during “on” time. There were a variety of secondary measures, including scales of motor function, quality of life, and depression.
At the end of the trial, dyskinesias in the placebo-treated group had worsened slightly, while in the safinamide-treated groups, they had improved slightly. However, neither of the differences between the active treatment groups and placebo were significant. “This may have been due to the low baseline DRS scores and the low incidence of troublesome dyskinesias,” Anand said.
In a post-hoc analysis, he showed that patients with the most severe baseline dyskinesias did significantly benefit from safinamide compared to placebo.
Both doses of safinamide improved total “on” time with no or minor dyskinesias. Patients on the low dose improved “on” time by 0.67 hours versus placebo, and those on the high dose improved by 0.83 hours versus placebo. “Off” time was significantly reduced in both active-treatment groups as well.
Significant improvements were also seen for both doses in activities of daily living, and for the higher dose in depression and motor scores. No new safety concerns emerged in this extension study, and adverse effects were similar among all three treatment groups.
“Our findings over a two-year treatment period suggest that taking safinamide in addition to levodopa and other dopaminergic treatments could help patients who continue to experience tremors and involuntary movement problems,” Anand said
The study was funded by Newron /Merck Serono of Switzerland.