Objective: This study evaluated the efficacy and safety outcomes of safinamide as a levodopa adjunct therapy in Asian and Caucasian patients with Parkinson’s disease.

Background: Safinamide is a selective and reversible monoamine oxidase B (MAO-B) inhibitor with a sodium channel inhibitory effect, and it inhibits stimulated glutamate release in the basal ganglia [1, 2]. In the SETTLE study, safinamide adjunct therapy significantly improved wearing-off in patients with PD and motor fluctuations [3].

Method: This is a post-hoc analysis of SETTLE study, a 24-week, double-blind, randomized, placebo-controlled study. The dose of safinamide was increased from 50 mg to 100 mg if no tolerability issues arose at Week 2. Primary outcome was change from baseline to Week 24 in daily ON-time without troublesome dyskinesia (ON-time). Unified Parkinson’s Disease Rating Scale (UPDRS) scores were also assessed as secondary outcomes.

Results: This analysis included 173 Asian and 371 Caucasian patients. Asian patients received higher doses of daily levodopa by body weight than Caucasian patients (13.09 mg/kg/day vs 10.41 mg/kg/day, P=0.0001). At Week 24, safinamide significantly increased daily ON-time relative to placebo by an LS mean of 0.83 hours in Asians and 1.05 hours in Caucasians. UPDRS Part III motor function benefits were statistically significant in Asians (-2.65 points relative to placebo, P=0.0118), but not Caucasians (-1.44 points relative to placebo, P=0.0576). Dyskinesia, the most common adverse event, was mostly mild among safinamide-treated Asians (mild/moderate/severe = 8.0%/3.4%/2.3%) and moderate among safinamide-treated Caucasians (mild/moderate/severe = 4.4%/9.3%/1.6%). None of the Asian safinamide-treated patients experienced treatment-emergent adverse events (TEAE) leading to study discontinuation, while 6.6% of Caucasian safinamide-treated patients discontinued the study due to TEAE.

Conclusion: Safinamide as a levodopa adjunct therapy is well-tolerated and effective in reducing motor fluctuations in both Asian and Caucasian patients.

References: [1] Morari M, Brugnoli A, Pisanò CA, et al. Sardina M, Safinamide differentially modulates in vivo glutamate and GABA release in the rat hippocampus and basal ganglia. J Pharmacol Exp Ther. 2018;364(2):198–206.
[2] Salvati P, Maj R, Caccia C, et al. Biochemical and electrophysiological studies on the mechanism of action of PNU-151774E, a novel antiepileptic compound. J Pharmacol Exp Ther. 1999;288(3):1151–1159 .
[3] Schapira AHV, Fox SH, Hauser RA, et al. Assessment of Safety and Efficacy of Safinamide as a Levodopa Adjunct in Patients With Parkinson Disease and Motor Fluctuations. JAMA Neurol. 2017;74(2):216-224.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/safinamide-as-an-adjunct-to-levodopa-therapy-in-asian-and-caucasian-patients-with-parkinsons-disease-and-motor-fluctuations-a-post-hoc-analysis-of-the-settle-study/