Division of Pulmonary, Critical Care and Sleep Medicine, University of California San Diego, La Jolla.
University of Toronto, ON, Canada.
Sleep. 2020 Feb 13;43(2). doi: 10.1093/sleep/zsz220.
To evaluate long-term safety and maintenance of efficacy of solriamfetol treatment for excessive daytime sleepiness in narcolepsy and obstructive sleep apnea (OSA).
Participants with narcolepsy or OSA who completed a prior solriamfetol study were eligible. A 2-week titration period was followed by a maintenance phase (up to 50 weeks). Efficacy was assessed by Epworth Sleepiness Scale (ESS) and Patient and Clinical Global Impression of Change (PGI-C and CGI-C, respectively). After approximately 6 months of treatment, a subgroup entered a 2-week placebo-controlled randomized withdrawal (RW) phase. Change in ESS from beginning to end of the RW phase was the primary endpoint; PGI-C and CGI-C were secondary endpoints. Safety was assessed throughout the study.
In the maintenance phase, solriamfetol-treated participants demonstrated clinically meaningful improvements on ESS, PGI-C, and CGI-C. In the RW phase, least squares mean change on ESS was 1.6 in participants continuing solriamfetol versus 5.3 in participants switched to placebo (p < .0001). For both secondary endpoints, higher percentages of participants receiving placebo were reported as worse at the end of the RW phase versus solriamfetol (p < .0001). Common treatment-emergent adverse events (TEAEs) with solriamfetol were headache, nausea, nasopharyngitis, insomnia, dry mouth, anxiety, decreased appetite, and upper respiratory tract infection; 27 (4.2%) participants experienced at least one serious TEAE, and 61 (9.5%) withdrew because of TEAEs.
This study demonstrated long-term maintenance of efficacy of solriamfetol under open-label and double-blind, placebo-controlled conditions. Safety profile of solriamfetol was consistent with previous 12-week studies; no new safety concerns were identified.
NCT02348632.
评估索里昂治疗发作性睡病和阻塞性睡眠呼吸暂停（OSA）患者日间过度嗜睡的长期安全性和疗效维持情况。
符合条件的参与者为完成先前索里昂研究的发作性睡病或 OSA 患者。先进行为期 2 周的滴定期，然后进入维持期（最长 50 周）。采用 Epworth 嗜睡量表（ESS）和患者和临床医生总体印象变化量表（PGI-C 和 CGI-C）评估疗效。治疗约 6 个月后，亚组进入为期 2 周的安慰剂对照随机撤药（RW）阶段。RW 阶段结束时 ESS 的变化是主要终点；PGI-C 和 CGI-C 是次要终点。整个研究期间评估安全性。
在维持期，索里昂治疗的参与者在 ESS、PGI-C 和 CGI-C 上均表现出具有临床意义的改善。在 RW 阶段，继续接受索里昂治疗的参与者 ESS 的最小二乘均值变化为 1.6，而切换至安慰剂的参与者为 5.3（p<0.0001）。对于这两个次要终点，在 RW 阶段结束时，更多接受安慰剂的参与者报告为更差（p<0.0001）。索里昂治疗的常见治疗相关不良事件（TEAEs）有头痛、恶心、鼻咽炎、失眠、口干、焦虑、食欲下降和上呼吸道感染；27（4.2%）名参与者出现至少一次严重 TEAE，61（9.5%）名参与者因 TEAEs 而退出。
这项研究表明，在开放标签和双盲、安慰剂对照条件下，索里昂的疗效维持时间长。索里昂的安全性与之前的 12 周研究一致；未发现新的安全性问题。
NCT02348632。
