Mattingly Gregory W, Turkoglu Osman, Chang Denise, Ward Caroline, Skubiak Taisa, Zhang Zhen, Cutler Andrew J
Washington University School of Medicine, Midwest Research Group, St. Louis, MO.
Otsuka Pharmaceutical Development and Commercialization, Inc., Princeton, NJ.
J Clin Psychopharmacol. 2025;45(5):454-462. doi: 10.1097/JCP.0000000000002020. Epub 2025 Jul 2.
Centanafadine (CTN) is a potential first-in-class norepinephrine, dopamine, and serotonin reuptake inhibitor (NDSRI) currently in development for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults. Safety, tolerability, and exploratory efficacy of CTN sustained release (SR) in adults were assessed over 52 weeks.
Adults were enrolled after completing a phase 3 pivotal trial or de novo. The monitoring schedule employed a screening (up to 28 d for de novo group only), 52-week open-label, and 10-day safety follow-up periods. Participants received CTN SR 400 mg total daily dose, twice daily. Safety assessments included treatment-emergent adverse events (TEAEs), clinical laboratories, vital signs, electrocardiogram measures, the Study Medication Withdrawal Questionnaire, and the Columbia-Suicide Severity Rating Scale. Exploratory efficacy was assessed using the Adult Investigator Symptom Rating Scale (AISRS) and the Clinical Global Impression of Severity (CGI-S). Safety was analyzed with a mixed-effect model; efficacy was reported using summary statistics.
Of 662 adults enrolled [mean (SD) age, 36.7 (10.1) y; 51.1% female; 82.9% white], 653 received CTN SR, and 345 completed the trial. Altogether, 61.4% reported ≥1 TEAE, mostly mild or moderate in severity; insomnia (8.0%), nausea (7.7%), diarrhea and headache (7.0% each) were most common. Eighty (12.3%) discontinued because of TEAEs. Serious adverse events occurred in 12 (1.8%) participants; none were CTN SR-related per investigators. AISRS total scores improved up to 57% and CGI-S by 1.5 points from baseline.
Results from this trial demonstrate that CTN SR 400 mg is safe and effective for long-term treatment of adults with ADHD.
森他法定（CTN）是一种潜在的一流去甲肾上腺素、多巴胺和5-羟色胺再摄取抑制剂（NDSRI），目前正处于研发阶段，用于治疗成人注意力缺陷多动障碍（ADHD）。对CTN缓释制剂（SR）在成人中的安全性、耐受性和探索性疗效进行了为期52周的评估。
成人在完成一项3期关键试验后入组或重新入组。监测计划包括一个筛查期（仅重新入组组最长为28天）、一个为期52周的开放标签期和一个为期10天的安全性随访期。参与者接受CTN SR，每日总剂量400mg，分两次服用。安全性评估包括治疗中出现的不良事件（TEAE）、临床实验室检查、生命体征、心电图测量、研究药物撤药问卷以及哥伦比亚自杀严重程度评定量表。使用成人研究者症状评定量表（AISRS）和临床总体印象严重程度量表（CGI-S）评估探索性疗效。安全性采用混合效应模型进行分析；疗效采用汇总统计数据报告。
在入组的662名成人中[平均（标准差）年龄为36.7（10.1）岁；51.1%为女性；82.9%为白人]，653人接受了CTN SR治疗，345人完成了试验。总计，61.4%的人报告了≥1次TEAE，大多为轻度或中度；失眠（8.0%）、恶心（7.7%）、腹泻和头痛（各7.0%）最为常见。80人（12.3%）因TEAE停药。12名（1.8%）参与者发生了严重不良事件；根据研究者判断，均与CTN SR无关。AISRS总分从基线改善了高达57%，CGI-S改善了1.5分。
该试验结果表明，400mg的CTN SR对成人ADHD的长期治疗是安全有效的。
