Abstract

Introduction

Excessive daytime sleepiness (EDS) in patients with obstructive sleep apnea (OSA) is associated with an increased risk of driving accidents. Solriamfetol, a dopamine/norepinephrine reuptake inhibitor, is approved in the US (Sunosi^®) for EDS associated with OSA (37.5-150 mg/day). This study evaluated solriamfetol’s effects on on-road driving performance in participants with EDS associated with OSA.

Methods

In each period of this randomized, double-blind, placebo-controlled, crossover study (NCT 02806895; EudraCT 2015-003930-28), driving performance during an on-road driving test was assessed at 2 hours and 6 hours postdose following 7 days of treatment with solriamfetol (150mg/day × 3, then 300mg/day × 4) or placebo. The primary endpoint—standard deviation of lateral position (SDLP), a measure of “weaving,” at 2 hours postdose—was compared between solriamfetol and placebo per time point using a repeated mixed-effects analysis of variance model.

Results

The study included 34 participants. Baseline characteristics reflected the broader OSA population (88% male; mean age=52 years; mean Epworth Sleepiness Scale score=14.4). SDLP at 2 hours postdose was statistically significantly lower following solriamfetol (least squares [LS] mean [standard error; SE], 18.83cm [0.63]) compared with placebo (19.92cm [0.63]): LS mean difference, -1.08cm; 95% confidence interval (CI), -1.85, -0.32; P=0.0062 (incomplete driving tests: solriamfetol, n=1; placebo, n=4), indicating better performance with solriamfetol. At 6 hours postdose, SDLP following solriamfetol (LS mean[SE], 19.24cm [0.63]) was statistically significantly lower compared with placebo (20.04cm [0.63]): LS mean difference, -0.80cm; 95% CI, -1.58, -0.03; P=0.0432 (incomplete driving tests: solriamfetol, n=3; placebo, n=7). Common adverse events (≥5%) with solriamfetol were headache, nausea, insomnia, dizziness, and agitation.

Conclusion

Solriamfetol (300mg/day) improved SDLP, an important measure of driving performance, at 2 and 6 hours in participants with EDS associated with OSA.

Support

Jazz Pharmaceuticals

中文翻译：

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0673索里亚米醇对白天过度嗜睡与阻塞性睡眠呼吸暂停相关参与者的驾驶性能的影响

摘要

介绍

阻塞性睡眠呼吸暂停（OSA）患者白天过度嗜睡（EDS）与驾驶事故的风险增加相关。Solriamfetol，多巴胺/去甲肾上腺素再摄取抑制剂，被批准在美国（Sunosi ^®与OSA（37.5-150毫克/天）相关联），用于EDS。这项研究评估了solriamfetol对与OSA相关的EDS参与者的公路驾驶性能的影响。

方法

在这项随机，双盲，安慰剂对照的交叉研究（NCT 02806895; EudraCT 2015-003930-28）的每个阶段中，均在给药后2天和给药后6小时评估了公路驾驶测试中的驾驶性能索拉米非（150mg /天×3，然后300mg /天×4）或安慰剂治疗。使用重复混合效应方差分析，比较了每个时间点solriamfetol和安慰剂之间的主要终点-侧卧位标准偏差（SDLP），即“编织”的量度，在每个时间点进行了比较。

结果

该研究包括34名参与者。基线特征反映了更广泛的OSA人群（88％的男性；平均年龄= 52岁；平均Epworth嗜睡量表得分为14.4）。与安慰剂（19.92cm [0.63]）相比，服用索拉莫非酚后2小时的SDLP在统计学上显着降低（最小二乘法[LS]平均[标准误差； SE]为18.83cm [0.63]）：LS平均差为-1.08cm；95％置信区间（CI），-1.85，-0.32；P = 0.0062（不完全驾驶测试：solriamfetol，n = 1；安慰剂，n = 4），表明solriamfetol具有更好的性能。服药后6小时，索拉米非后的SDLP（LS均值[SE]，19.24cm [0.63]）与安慰剂（20.04cm [0.63]）相比在统计学上显着降低：LS平均差为-0.80cm；95％CI，-1.58，-0.03；P= 0.0432（不完整的驾驶考试：索莫米酚，n = 3；安慰剂，n = 7）。索莫米酚常见的不良事件（≥5％）为头痛，恶心，失眠，头晕和躁动。

结论

Solriamfetol（300mg /天）改善了与OSA相关的EDS参与者在2和6小时时的SDLP，SDLP是衡量驾驶性能的重要指标。

支持

爵士药业