Azetukalner, a Novel K V 7 Potassium Channel Opener, in Adults With Major Depressive Disorder

作者：Noam N. Butterfield, Constanza Luzon Rosenblut, Maurizio Fava, Christoph U. Correll, Anthony J. Rothschild, James W. Murrough, Sanjay J. Mathew, Gregory N. Beatch, Celene Grayson, Cynthia L. Harden, Jenny Qian, Joe McIntosh, Rostam Namdari, Christopher Kenney · 发表于：JAMA Network Open · 年份：2025 · DOI：10.1001/jamanetworkopen.2025.14278 · 被引用次数：9 · 研究领域：Treatment of Major Depression、Electroconvulsive Therapy Studies、Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes

Importance: Available antidepressants provide inadequate therapeutic responses in many patients with major depressive disorder (MDD), highlighting a substantial unmet need. Objective: To evaluate the efficacy and safety of azetukalner, a novel, potent KV7 potassium channel opener, in participants with MDD. Design, Setting, and Participants: X-NOVA was a multicenter, proof-of-concept, phase 2, randomized, double-blind, parallel-group, placebo-controlled clinical trial that evaluated azetukalner in participants (adults aged ≥18 to ≤65 years) with moderate to severe MDD in a current depressive episode. Participants were enrolled between April 2022 and October 2023, and data analysis occurred from January 2023 to January 2024. Intervention: Participants were randomized (1:1:1) to 10 mg of azetukalner, 20 mg of azetukalner, or placebo orally once daily with food for 6 weeks, with a 4-week follow-up. Concomitant antidepressant medications were not permitted. Main Outcomes and Measures: The primary efficacy end point was change in Montgomery-Åsberg Depression Rating Scale (MADRS) score at week 6. Secondary end points included change from baseline at week 6 in the Snaith-Hamilton Pleasure Scale (SHAPS) and Beck Anxiety Inventory. Exploratory end points included change in the Hamilton Depression Rating Scale, 17-Item (HAM-D17) score and change in MADRS at week 1. Frequency and severity of treatment-emergent adverse events (TEAEs) were recorded. Results: Altogether, 168 participants we...