Efficacy and safety of safinamide as an add-on therapy to L-DOPA for patients with Parkinson's disease: A randomized, double-blind, placebo-controlled, phase II/III study

Abstract

Introduction: Safinamide is a reversible and selective monoamine oxidase-B (MAO-B) and sodium channel inhibitor with demonstrated efficacy in mid-to late-stage Parkinson's disease (PD) as an adjunct to L-DOPA. This study aimed to confirm the efficacy and safety of safinamide in PD patients with wearing-off. Methods: This 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study included Japanese PD patients with wearing-off on L-DOPA treatment. Patients were randomized to receive placebo (P), safinamide 50 mg/day (S50), or safinamide 100 mg/day (S100). The primary endpoint was the change from baseline in mean daily ON-time without troublesome dyskinesias (ON-time). Other measures included the changes in mean daily OFF-time, the unified Parkinson's disease rating scale (UPDRS) score, and the PDQ-39 summary index. Results: A total of 406 subjects were randomized, of whom 349 completed the study. Baseline characteristics were balanced. Differences in the change of mean daily ON-time at Week 24 compared with the P group were 1.39 h (p = 0.0002) in the S50 group and 1.66 h (p < 0.0001) in the S100 group. Changes from baseline in mean daily OFF-time, UPDRS Part II total score (OFF phase), UPDRS Part III total score (ON phase), and UPDRS Part I also showed significant improvements. Adverse events occurred in 58.9%, 60.2%, and 61.4% of the P, S50, and S100 groups, respectively. The most common adverse drug reactions were dyskinesias (2.1%, 8.3%, and 10.6%) and visual hallucinations (1.4%, 3.0%, and 4.5%). Conclusion: As an adjunct to L-DOPA, safinamide safely increased ON-time and improved PD symptoms/signs in PD patients with wearing-off.

Impact of SAfinamide on Depressive Symptoms in Parkinson’s Disease Patients (SADness-PD Study): A Multicenter Retrospective Study

“…Based on the UPDRS analysis, our real clinical practice study confirms that safinamide may improve motor symptoms, motor complications, and daily life activities in PD patients, which is in agreement with previous reports [2][3][4][5]29,30]. Supporting these findings, a recent meta-analysis that evaluated both motor function and the activities of daily life in PD patients treated with safinamide suggested that the drug not only improves scores for UPDRS Parts II and III over placebo [31] but also improves motor function, motor fluctuations, and quality of life in PD [31].…”

“…Safinamide is a reversible and selective monoamine oxidase B inhibitor (MAOIB) and glutamate release modulator [1]. Several trials have demonstrated that in advanced Parkinson's disease (PD), safinamide significantly improves "ON" time without causing troublesome dyskinesia, reduces "OFF" time, and improves scores on the Unified Parkinson's Disease Rating Scale (UPDRS), improving quality of life [2][3][4][5][6]. Thus, it is approved for the treatment of mid-to-late fluctuating PD patients as an add-on therapy alongside stable doses of levodopa alone or in combination with others drugs.…”

Overall Efficacy and Safety of Safinamide in Parkinson’s Disease: A Systematic Review and a Meta-analysis

“…Therefore, six studies met the inclusion criteria for qualitative and quantitative synthesis (009, 015, 016, MOTION, SETTLE, and ME2125-3) (Fig. 1) [28][29][30][31][32]. The screening process retrieved one completed study with not yet published data, NCT00605683 (MOTION).…”

“…2) and daily OFF-time (Fig. 3) were assessed in PDwMF patients treated with l-dopa [30][31][32]. Safinamide 100 mg significantly increased ON-time without troublesome dyskinesia (MD = 0.95 h; 95% CI from 0.41 to 1.49; p = 0.0006; I 2 = 70%) and decreased OFF-time (MD = − 1.06 hours; 95% CI from − 1.60 to − 0.51; p = 0.0001; I 2 = 76%).…”

“…ON-time with troublesome dyskinesia was evaluated only in two studies in PDwMF [30,32]. Nonsignificant differences were observed for both safinamide 100 mg (MD = 0.14 h; 95% CI from − 0.03 to 0.30; p = 0.10; I 2 = 0%) and 50 mg (MD = 0.00 h; 95% CI from − 0.17 to 0.18; p = 0.96; I 2 = 0%) (Fig.…”