Center for Psychiatry and Behavioral Medicine, Inc., Las Vegas, NV, USA.
Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA.
CNS Drugs. 2024 Nov;38(11):891-907. doi: 10.1007/s40263-024-01120-0. Epub 2024 Oct 7.
Viloxazine ER (extended-release capsules; Qelbree) is a nonstimulant medication that has been approved by the United States Food and Drug Administration (FDA) for treatment of attention-deficit/hyperactivity disorder (ADHD) in children (> 6 years old) and adults. This phase 3 open-label extension to a pivotal phase 3, double-blind trial evaluated the long-term safety and continued efficacy of viloxazine ER in adults with ADHD.
This was a multicenter, flexible-dose, open-label extension to a phase III, double-blind, placebo-controlled trial (NCT04016779). Viloxazine ER was initiated at 200 mg/day and adjusted (between 200 and 600 mg/day) to achieve optimal efficacy and tolerability. Trial enrollment was halted temporarily (24 March 2020 to 23 July 2020) due to the coronavirus disease 2019 (COVID-19) pandemic. Participants completing double-blind treatment during that time were offered delayed enrollment upon trial requalification. Safety outcomes were the primary objectives. Secondary objectives were efficacy outcomes, including the ADHD Investigator Symptom Rating Scale (AISRS), and were assessed relative to double-blind baseline (or trial re-entry baseline for those whose enrollment was delayed by the COVID-19 pandemic).
Overall, 159 participants (133 immediate and 26 delayed rollover) received viloxazine ER, with a mean exposure of 265 ± 254.9 days. Adverse events (AEs) included (> 10% incidence) insomnia (13.8%), nausea (13.8%), headache (10.7%), and fatigue (10.1%). AEs led to discontinuation for 17.6% of participants [most commonly insomnia (2.5%), nausea (2.5%), and fatigue (1.9%)]. AISRS total score [baseline mean ± standard deviation (SD): 37.9 ± 6.3] improved by the first follow-up visit (-11.4 ± 9.5; week 2) with continued improvement at subsequent visits (last on-study visit: -18.2 ± 11.54). Similar patterns of improvement were seen for other measures of efficacy, including quality of life and executive function. Following initial dose optimization, most participants (73%) used viloxazine ER doses ≥ 400 mg/day, with 36% using doses of 600 mg/day.
Long-term viloxazine ER use was well tolerated, with no new long-term safety findings. Improvements in ADHD symptoms and associated measures were sustained throughout trial participation. In total, 73% percent of adult participants in this long-term study used viloxazine ER doses of 400 mg or more during maintenance treatment.
Clinicaltrials.gov Identifier: NCT04143217.
Viloxazine ER（延长释放胶囊；Qelbree）是一种非兴奋剂药物，已被美国食品和药物管理局（FDA）批准用于治疗儿童（> 6 岁）和成人的注意力缺陷/多动障碍（ADHD）。这项关键性的 3 期双盲试验的 3 期开放标签扩展评估了 ADHD 成人中 Viloxazine ER 的长期安全性和持续疗效。
这是一项多中心、灵活剂量、开放标签的 3 期双盲、安慰剂对照试验（NCT04016779）的扩展。Viloxazine ER 起始剂量为 200mg/天，并进行调整（200-600mg/天）以达到最佳疗效和耐受性。由于 2019 年冠状病毒病（COVID-19）大流行，试验于 2020 年 3 月 24 日至 2020 年 7 月 23 日暂时停止入组。在这段时间内完成双盲治疗的参与者在重新符合条件后被提供延迟入组。安全性结果是主要目标。次要目标是疗效结果，包括 ADHD 研究者症状评定量表（AISRS），并相对于双盲基线（或对于因 COVID-19 大流行而延迟入组的参与者，相对于试验重新入组基线）进行评估。
共有 159 名参与者（133 名立即和 26 名延迟滚入）接受了 Viloxazine ER 治疗，平均暴露时间为 265 ± 254.9 天。不良事件（AE）包括（发生率> 10%）失眠（13.8%）、恶心（13.8%）、头痛（10.7%）和疲劳（10.1%）。AE 导致 17.6%的参与者停药[最常见的是失眠（2.5%）、恶心（2.5%）和疲劳（1.9%）]。AISRS 总分[基线平均值±标准差（SD）：37.9 ± 6.3]在第一次随访时下降了 11.4 ± 9.5（第 2 周），随后的随访中持续改善（最后一次研究访视：-18.2 ± 11.54）。其他疗效指标也出现了类似的改善模式，包括生活质量和执行功能。在初始剂量优化后，大多数参与者（73%）使用了≥400mg/天的 Viloxazine ER 剂量，其中 36%使用了 600mg/天的剂量。
长期使用 Viloxazine ER 耐受性良好，无新的长期安全性发现。ADHD 症状和相关指标的改善在整个试验过程中持续存在。总的来说，这项长期研究中有 73%的成年参与者在维持治疗期间使用了 400mg 或更高剂量的 Viloxazine ER。
ClinicalTrials.gov 标识符：NCT04143217。
