:Study Objective:SPN-812 (extended-release viloxazine) is a structurally distinct, bicyclic, Serotonin Norepinephrine Modulating Agent (SNMA) in development as a treatment for attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. This Phase 3, randomized, double-blind study (P301) evaluated the efficacy and safety of once-daily SPN-812 at doses of 100 and 200 mg compared to placebo in children ages 6-11yrs with ADHD.Method:Inclusion criteria required subjects have a confirmed Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) ADHD diagnosis, ADHD-Rating Scale-5 (ADHD-RS-5) score ≥28, a Clinical Global Impression-Severity score ≥4, and be free of ADHD medication ≥1 week before randomization. This investigation was conducted at 34 study sites in the United States. Subjects (N=477) were randomized 1:1:1 to placebo:100 mg SPN-812:200 mg SPN-812. The 6-week treatment period included up to 1 week of titration and 5 weeks of maintenance (intent-to-treat population: N=460; placebo=155, 100 mg=147, 200 mg=158). The primary efficacy endpoint was the change from baseline (CFB) at end of study (EOS) in ADHD-RS-5 total score. Key secondary endpoints included Clinical Global Impression-Improvement (CGI-I) scores at EOS, and CFB at EOS in Conners 3-Parent Short Form (Conners 3-PS) Composite T-score and in Weiss Functional Impairment Rating Scale-Parent Version (WFIRS-P) total average score. Safety assessments included adverse events (AEs), laboratory tests, vital signs, physical exams, electrocardiograms, and the Columbia-Suicide Severity Rating Scale.Results:Compared to placebo, a significantly greater improvement in ADHD-RS-5 total score was observed in the 100 mg and 200 mg SPN-812 treatment groups beginning at week 1 (p=0.0004, p=0.0244; respectively) through EOS (p=0.0004, p<0.0001; respectively). Significant improvement at EOS for both 100 mg and 200 mg SPN-812 compared to placebo was also observed in CGI-I score (p=0.0020, p<0.0001; respectively), Connors 3-PS Composite T-score (p=0.0003, p=0.0002; respectively), and in WFIRS-P total average score (p=0.0019, p=0.0002, respectively). The most common (≥5%) treatment-related AEs reported were somnolence, decreased appetite, and headache.Conclusions:In this study, SPN-812 at 100 mg and 200 mg doses met the primary and secondary objectives with statistical significance. AE-related dropouts were ≤5%, indicating SPN-812 treatment was well tolerated.This study is an encore of a poster presentation at the 2019 Annual Meeting of the American Academy of Child and Adolescent Psychiatry (AACAP).Funding Acknowledgements:This research was funded by Supernus Pharmaceuticals, Inc., Rockville, MD.

中文翻译：

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111 3 期、随机、双盲、安慰剂对照研究 (P301) 评估缓释维洛沙嗪对 ADHD 儿童的疗效和安全性

：研究目的：SPN-812（缓释维恶嗪）是一种结构独特的双环血清素去甲肾上腺素调节剂 (SNMA)，正在开发用于治疗儿童和青少年注意力缺陷/多动障碍 (ADHD)。这项 3 期、随机、双盲研究 (P301) 在 6-11 岁患有 ADHD 的儿童中评估了每日一次 SPN-812 在 100 和 200 毫克剂量下与安慰剂相比的疗效和安全性。方法：纳入标准要求受试者已确认《精神疾病诊断和统计手册》第 5 版 (DSM-5) ADHD 诊断，ADHD-Rating Scale-5 (ADHD-RS-5) 评分≥28，临床总体印象严重程度评分≥4，并且是随机分组前 1 周以上未服用 ADHD 药物。这项调查是在美国的 34 个研究地点进行的。受试者 (N=477) 以 1:1 的比例随机分配：1 至安慰剂：100 毫克 SPN-812：200 毫克 SPN-812。6 周的治疗期包括长达 1 周的滴定和 5 周的维持（意向治疗人群：N=460；安慰剂=155、100 mg=147、200 mg=158）。主要疗效终点是 ADHD-RS-5 总分在研究结束时 (EOS) 与基线 (CFB) 的变化。关键的次要终点包括 EOS 的临床全球印象改善 (CGI-I) 分数，以及 EOS 的 CFB 在 Conners 3-Parent Short Form (Conners 3-PS) Composite T-score 和 Weiss 功能障碍评定量表 - 父母版 ( WFIRS-P) 总平均分。安全性评估包括不良事件 (AE)、实验室测试、生命体征、体格检查、心电图和哥伦比亚自杀严重程度评定量表。结果：与安慰剂相比，从第 1 周开始（p=0.0004，p=0.0244；分别）到 EOS（p=0.0004，p< 0.0001；分别）。在 CGI-I 评分（分别为 p=0.0020，p<0.0001）、Connors 3-PS 综合 T 评分（p=0.0003， p=0.0002；分别）和 WFIRS-P 总平均分（分别为 p=0.0019，p=0.0002）。报告的最常见 (≥5%) 与治疗相关的 AE 是嗜睡、食欲下降和头痛。结论：在本研究中，100 mg 和 200 mg 剂量的 SPN-812 达到了具有统计学意义的主要和次要目标。与 AE 相关的辍学率≤5%，表明 SPN-812 治疗耐受性良好。