在发作性睡病患者中进行的司来吉兰随机3期研究的功能结局、工作生产力和生活质量测量。

Measures of functional outcomes, work productivity, and quality of life from a randomized, phase 3 study of solriamfetol in participants with narcolepsy.

作者信息

Emsellem Helene A, Thorpy Michael J, Lammers Gert Jan, Shapiro Colin M, Mayer Geert, Plazzi Giuseppe, Chen Dan, Carter Lawrence P, Villa Kathleen F, Lee Lawrence, Menno Diane, Black Jed, Dauvilliers Yves

机构信息

The Center for Sleep & Wake Disorders, Chevy Chase, MD, USA; George Washington University Medical Center, Washington, DC, USA.

Montefiore Medical Center, Bronx, NY, USA.

出版信息

Sleep Med. 2020 Mar;67:128-136. doi: 10.1016/j.sleep.2019.11.1250. Epub 2019 Dec 4.

DOI:10.1016/j.sleep.2019.11.1250

PMID:31926465

Abstract

OBJECTIVE

Solriamfetol (formerly JZP-110), a dopamine/norepinephrine reuptake inhibitor, is approved in the US to improve wakefulness in adults with excessive daytime sleepiness associated with narcolepsy (75-150 mg/d) or obstructive sleep apnea (37.5-150 mg/d). In a randomized, double-blind, placebo-controlled trial in participants with narcolepsy, effects of solriamfetol on functional status, health-related quality of life (HRQoL), and work productivity were evaluated.

METHODS

Participants with narcolepsy (N = 239) were randomized to solriamfetol 75, 150, or 300 mg, or placebo for 12 weeks. Outcome measures included the Functional Outcomes of Sleep Questionnaire short version (FOSQ-10), 36-Item Short Form Health Survey version 2 (SF-36v2), and Work Productivity and Activity Impairment questionnaire for Specific Health Problem (WPAI:SHP). A mixed-effects model with repeated measures was used for comparisons vs placebo.

RESULTS

At week 12, solriamfetol increased FOSQ-10 total score, with greatest mean difference from placebo (95% CI) at 300 mg (1.45 [0.31, 2.59]). On SF-36v2, improvements vs placebo were observed in physical component summary scores (300 mg: 2.22 [0.04, 4.41]) and subscales of role physical, general health, and vitality. On WPAI:SHP, solriamfetol 150 mg reduced overall work impairment vs placebo (-15.5 [-29.52, -1.47]), and 150 and 300 mg reduced activity impairment vs placebo (-10.05 [-19.48, -0.62] and -13.49 [-23.19, -3.78], respectively). Most treatment-emergent adverse events (TEAEs) were mild or moderate in severity. Common TEAEs were headache, nausea, decreased appetite, nasopharyngitis, dry mouth, and anxiety.

CONCLUSIONS

Solriamfetol improved measures of functional status, HRQoL, and work productivity, particularly at the 150- and 300-mg doses. Most TEAEs were mild to moderate.

TRIAL REGISTRATION

ClinicalTrials.gov identifier NCT02348593, EudraCT number 2014-005487-15.

摘要

目的

索利那非托（原JZP - 110）是一种多巴胺/去甲肾上腺素再摄取抑制剂，在美国被批准用于改善患有发作性睡病（75 - 150毫克/天）或阻塞性睡眠呼吸暂停（37.5 - 150毫克/天）且伴有日间过度嗜睡的成年人的清醒状态。在一项针对发作性睡病患者的随机、双盲、安慰剂对照试验中，评估了索利那非托对功能状态、健康相关生活质量（HRQoL）和工作效率的影响。

方法

将发作性睡病患者（N = 239）随机分为索利那非托75毫克、150毫克、300毫克组或安慰剂组，为期12周。结果测量指标包括睡眠问卷简版功能结果（FOSQ - 10）、健康调查简表第2版（SF - 36v2）以及特定健康问题的工作效率和活动障碍问卷（WPAI:SHP）。采用重复测量的混合效应模型与安慰剂进行比较。

结果

在第12周时，索利那非托提高了FOSQ - 10总分，300毫克组与安慰剂组的平均差异最大（95%CI）为1.45[0.31, 2.59]。在SF - 36v2上，与安慰剂相比，身体成分总结得分（300毫克组：2.22[0.04, 4.41]）以及角色身体、总体健康和活力子量表均有改善。在WPAI:SHP上，150毫克索利那非托与安慰剂相比减少了总体工作障碍（-15.5[-29.52, -1.47]），150毫克和300毫克组与安慰剂相比减少了活动障碍（分别为-10.05[-19.48, -0.62]和-13.49[-23.19, -3.78]）。大多数治疗中出现的不良事件（TEAE）严重程度为轻度或中度。常见的TEAE有头痛、恶心、食欲减退、鼻咽炎、口干和焦虑。