达力雷汀对慢性失眠障碍患者睡眠结构的影响：两项随机 3 期临床研究的汇总事后分析。

Effect of daridorexant on sleep architecture in patients with chronic insomnia disorder: a pooled post hoc analysis of two randomized phase 3 clinical studies.

机构信息

Idorsia Pharmaceuticals Ltd, Allschwil, Switzerland.

Department of Clinical Research, University of Basel, Schanzenstrasse, Basel.

出版信息

Sleep. 2024 Nov 8;47(11). doi: 10.1093/sleep/zsae098.

DOI:10.1093/sleep/zsae098

PMID:38644625

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11543623/

Abstract

STUDY OBJECTIVES

Post hoc analysis to evaluate the effect of daridorexant on sleep architecture in people with insomnia, focusing on features associated with hyperarousal.

METHODS

We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). We analyzed sleep-wake transition probabilities, EEG spectra, and sleep spindle properties including density, dispersion, and slow oscillation phase coupling. The wake EEG similarity index (WESI) was determined using a machine learning algorithm analyzing the spectral profile of the EEG.

RESULTS

At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities (p < .05) and increased the probability of transitions from wake-to-N1 (p < .05), N2 (p < .05), and REM sleep (p < .05), as well as from N1-to-N2 (p < .05) compared to baseline and placebo. Daridorexant 50 mg decreased relative beta power during wake (p = .011) and N1 (p < .001) compared to baseline and placebo. During the wake, relative alpha power decreased (p < .001) and relative delta power increased (p < .001) compared to placebo. Daridorexant did not alter EEG spectra bands in N2, N3, and REM stages or in sleep spindle activity. Daridorexant decreased the WESI score during wake compared to baseline (p = .004). Effects with 50 mg were consistent between months 1 and 3 and less pronounced with 25 mg.

CONCLUSIONS

Daridorexant reduced EEG features associated with hyperarousal as indicated by reduced wake-to-wake transition probabilities and enhanced spectral features associated with drowsiness and sleep during wake and N1.

CLINICAL TRIALS

ClinicalTrials.gov NCT03545191: study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants with insomnia disorder. URL: Study Details | study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants with insomnia disorder | ClinicalTrials.gov ClinicalTrials.gov NCT03575104:study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants who experience difficulties sleeping. URL: study details | study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants who experience difficulties sleeping | ClinicalTrials.gov.

摘要

研究目的

事后分析评估达理多雷克斯坦对失眠患者睡眠结构的影响，重点关注与过度觉醒相关的特征。

方法

我们研究了两项随机 3 期临床试验（Clinicaltrials.gov：NCT03545191 和 NCT03575104）中慢性失眠障碍成年人的睡眠结构，这些试验调查了达理多雷克斯坦治疗 3 个月（安慰剂、达理多雷克斯坦 25mg、达理多雷克斯坦 50mg）的情况。我们分析了睡眠-觉醒转换概率、脑电图谱和睡眠纺锤体特性，包括密度、分散度和慢振荡相位耦合。使用分析 EEG 频谱特征的机器学习算法确定了觉醒脑电图相似性指数（WESI）。

结果

在第 3 个月，达理多雷克斯坦 50mg 降低了觉醒到觉醒的转换概率（p<0.05），并增加了从觉醒到 N1（p<0.05）、N2（p<0.05）和 REM 睡眠（p<0.05）的转换概率，以及从 N1 到 N2（p<0.05）的转换概率，与基线和安慰剂相比。与基线和安慰剂相比，达理多雷克斯坦 50mg 降低了觉醒时的相对β功率（p=0.011）和 N1 时的相对β功率（p<0.001）。在觉醒期间，相对α功率降低（p<0.001），相对δ功率升高（p<0.001），与安慰剂相比。达理多雷克斯坦并未改变 N2、N3 和 REM 期或睡眠纺锤体活动中的脑电图谱带。与基线相比，达理多雷克斯坦在觉醒时降低了 WESI 评分（p=0.004）。50mg 的作用在第 1 个月和第 3 个月之间是一致的，而 25mg 的作用则不那么明显。

结论

达理多雷克斯坦降低了与过度觉醒相关的脑电图特征，表现为觉醒到觉醒的转换概率降低，以及在觉醒和 N1 时与困倦和睡眠相关的脑电图谱特征增强。

临床试验

ClinicalTrials.gov NCT03545191：评估 ACT-541468（达理多雷克斯坦）在失眠障碍成人和老年人中的疗效和安全性的研究。网址：研究详情|评估 ACT-541468（达理多雷克斯坦）在失眠障碍成人和老年人中的疗效和安全性的研究|ClinicalTrials.gov。ClinicalTrials.gov NCT03575104：评估 ACT-541468（达理多雷克斯坦）在睡眠困难的成人和老年人中的疗效和安全性的研究。网址：研究详情|评估 ACT-541468（达理多雷克斯坦）在睡眠困难的成人和老年人中的疗效和安全性的研究|ClinicalTrials.gov。