American Academy of Neurology (AAN) 63rd Annual Meeting

April 9-16, 2011; Honolulu, HI

Poster

Investigators Update 2-Year Data on Safinamide Use in Patients With Parkinson’s Disease

A 2-year trial of patients with Parkinson’s disease (PD) and motor fluctuations found that the addition of daily safinamide increased the amount of time each day in which patients experienced symptom relief with levodopa (ON time) and little to no dyskinesia. Safinamide is a novel agent being investigated as an adjunct therapy to dopamine agonists for patients who have early PD and as an adjunct to levodopa therapy for patients in the mid- to late stages of PD. The oral drug has dopaminergic and nondopaminergic mechanisms of action and increases dopamine levels through selective inhibition of monoamine oxidase (MAO)-B, dopamine reuptake, and glutamate release.

In a two-part investigation of safinamide use, consisting of a 6-month phase 3 clinical trial (Study 016) and an 18-month extension study (Study 018), investigators assessed the safety and efficacy of 50-mg and 100-mg daily doses of safinamide in patients with mid- to late-stage PD. Updated 24-month data were presented in a poster session at the AAN meeting. The poster was titled First Long-Term (2-year) Controlled Study to Evaluate Treatment with Safinamide as Add-on to Levodopa in Patients with Parkinson’s Disease and Motor Fluctuations.

Study 016 included 669 patients aged 30 to 80 years who had idiopathic PD (<stage V on the Hoehn and Yahr scale) for at least 3 years and had received a prescription for levodopa during that time. Study investigators randomized participants to receive 6 months of daily safinamide 50 mg (n=223), safinamide 100 mg (n=224), or placebo (n=222). Patients who completed all 24 weeks of the clinical trial and who were adherent to their assigned therapeutic regimen, experienced no significant adverse events, and were still <stage V on the Hoehn and Yahr scale at trial completion could elect to continue with Study 018 (n=544). Protocol called for patients continuing on with Study 018 to receive the same therapy that had been assigned to them in Study 016; patients who had been taking safinamide 100 mg but were unable to tolerate the regimen were permitted to switch to the 50-mg dose of safinamide in Study 018. The 18-month extension study allowed for changes in dosing for levodopa and other PD medications and allowed patients to be initiated on new PD medications, with the exception of  MAO inhibitors.

The primary end point of study 018 was the degree of improvement from baseline level in Dyskinesia Rating Scale (DRS) scores during ON time, and the final analyses considered data for Study 016’s entire intent-to-treat population. Although DRS scores worsened for those patients assigned to placebo and improved slightly for patients randomized to either safinamide dose, the change observed in mean DRS score from baseline did not differ significantly between the three cohorts. The authors hypothesized that the low number of participants who had been experiencing severe dyskinesia at enrollment likely contributed to the failure of Study 018 to meet its primary end point.

A post hoc analysis of data for patients who had a DRS score >4 at baseline showed significant improvement in ON time DRS scores at 24 weeks with safinamide 100 mg versus placebo (P=.03). Patients in this subgroup assigned to safinamide 100 mg were more likely to have their levodopa dose decreased compared with patients randomized to safinamide 50 mg or placebo (15.8% vs 19.8% vs 26.3%, respectively). The authors noted that, overall, patients in the safinamide 100-mg arm demonstrated greater improvement in motor function, nonmotor symptoms such as depression and activities of daily living, and clinical status compared with patients in the other study groups.

At the end of Study 016, patients taking safinamide experienced an increase in the average amount of ON time each day with no/minor dyskinesia and a decrease in the average amount of OFF time (time during which the medication was wearing off or ineffective and failed to control dyskinesia) compared with patients given placebo. The authors noted that the benefits seen with safinamide persisted at 2 years, with a mean increase in daily ON time with no/minor dyskinesia at 24 months of 0.67 hours in the 50-mg cohort and 0.83 hours in the 100-mg arm as compared with placebo. Daily OFF time decreased a mean of 0.62 hours in the safinamide 50-mg arm and 0.75 hours in the 100-mg group as compared with placebo.

A safety analysis found similar 2-year rates of serious adverse events, deaths, and discontinuations due to adverse events across all study arms. Completion rates among all three groups were also high. The authors reported no new safety concerns during the extension study.

This study was funded by Newron and Merck Serono S.A.-Geneva.