Objective: To evaluate the efficacy of safinamide for mood and pain by a post-hoc analysis of the Japanese phase 2/3 double-blind study (JapicCTI-153056) in patients with Parkinson’s disease (PD) and wearing-off phenomenon.

Background: Safinamide is a sodium channel blocker with selective and reversible MAO-B inhibitory effects. Mood symptoms and pain in PD have been shown to affect quality of life significantly. The non-dopaminergic and dopaminergic actions of safinamide may alleviate depressive symptom and pain in patients with PD [1, 2].

Method: The endpoints for this analysis were calculated as least square mean (LSM) changes from baseline at Week 24 (LOCF) in the UPDRS Part I item 3 (depression), item 4 (apathy), and Part II item 17 (sensory symptoms including pain). Subgroup analyses by improvement in wearing-off, baseline symptoms and concomitant drug were also performed. For the comparison between groups, analysis of covariance was performed with the treatment groups as a fixed effect and the baseline values as a covariance.

Results: LSM changes in the depression score in the placebo (PBO), safinamide 50-mg and 100-mg groups were 0.07, −0.06 (p = 0.0095 vs PBO), and −0.09 (p = 0.0024), respectively. The 100-mg dose improved apathy scores in the population with apathy at baseline (p = 0.0127). LSM changes in the sensory symptoms score during the OFF phase were 0.08 in the PBO, −0.15 (p = 0.0133) in the 50-mg, and −0.18 (p = 0.0054) in the 100-mg group. We observed an interrelationship between depression and wearing-off: Notable reductions in depression were associated with a change in daily ON-time ≥ 1 hour, and the presence of depression and/or apathy at baseline was associated with a greater increase in daily ON-time in the 100-mg group. On the other hand, the changes in the sensory symptoms were irrespective of the improvement in wearing-off. Rather, the presence of moderate-to-severe bradykinesia or early-morning dystonia at baseline resulted in numerically greater effect sizes in the sensory symptoms during the OFF phase.

Conclusion: Safinamide could provide particular benefits for patients with PD who have depression, apathy and/or who have pain during the OFF phase.

References: [1] Huang YH, Chen JH, Loh EW, Chan L, Hong CT. The effect of monoamine oxidase-B inhibitors on the alleviation of depressive symptoms in Parkinson’s disease: meta-analysis of randomized controlled trials. Ther Adv Psychopharmacol. 2021;11:1-9. [2] Qureshi AR, Rana AQ, Malik SH, Rizvi SFH, Akhter S, Vannabouathong C, Sarfraz Z, Rana R. Comprehensive Examination of Therapies for Pain in Parkinson’s Disease: A Systematic Review and Meta-Analysis. Neuroepidemiology. 2018;51(3-4): 190-206.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/effects-of-safinamide-adjunct-therapy-on-non-motor-symptoms-in-patients-with-parkinsons-disease-a-post-hoc-analysis-of-the-japanese-phase-2-3-study/