A double-blind, randomized, multicenter, phase 2b study of the safety and efficacy of suvecaltamide in essential tremor

Introduction: Effective treatments for essential tremor (ET) are needed. EveresT (NCT05122650) examined the efficacy and safety of suvecaltamide in patients with moderate to severe ET. Methods: In this phase 2 b, 12-week, double-blind, placebo-controlled, parallel-group, multicenter study, participants were equally randomized to once-daily placebo (n = 104) or suvecaltamide 10 mg (n = 105), 20 mg (n = 104), or 30 mg (n = 107). The primary endpoint was mean change from baseline to week 12 on The Essential Tremor Rating Assessment Scale (TETRAS) composite outcome score, which is a composite of the sum of modified items 1–11 of the TETRAS-Activities of Daily Living (TETRAS-ADL) subscale and modified items 6 and 7 of the TETRAS-Performance Subscale. The key secondary endpoint was the proportion of participants with ≥1-point improvement at week 12 on the Clinical Global Impression of Severity (CGI-S). Results: EveresT did not meet its primary endpoint; however, dose-related numerical improvements for suvecaltamide versus placebo were observed for the primary and multiple secondary endpoints, including TETRAS-ADL. At week 12, the mean difference between suvecaltamide 30 mg and placebo on the TETRAS composite score was −0.91 (95% confidence interval, −2.88, 1.06; P = 0.3626); 62.8% (52.9, 72.6) of participants improved ≥1 point at week 12 on the CGI-S with suvecaltamide 30 mg versus 50.0% (40.2, 59.8) with placebo (nominal P = 0.0771). Most common adverse effects with suvecaltamide 30 mg included dizziness (11.4%), paresthesia (8.6%), and insomnia, fatigue, somnolence, and worsening tremor (each 6.7%). Conclusion: Suvecaltamide did not achieve statistically significant improvements on the primary or key secondary efficacy endpoints compared with placebo.