Idorsia Pharmaceuticals Ltd, Hegenheimermattweg 91, 4123, Allschwil, Switzerland.
Department of Clinical Research, University of Basel, Schanzenstrasse 55, 4031, Basel, Switzerland.
CNS Drugs. 2023 Jul;37(7):639-653. doi: 10.1007/s40263-023-01020-9. Epub 2023 Jul 21.
Daridorexant, a dual orexin receptor antagonist approved in early 2022, reduces wake after sleep onset without reducing the number of awakenings in patients with insomnia. The objective of this post hoc analysis was to explore the effect of daridorexant on the number, duration, and distribution of night-time wake bouts, and their correlation with daytime functioning.
Adults with insomnia disorder were randomized 1:1:1:1:1:1 to placebo, zolpidem 10 mg, or daridorexant 5, 10, 25, or 50 mg in a phase II dose-finding study, and 1:1:1 to placebo or daridorexant 25 or 50 mg in a pivotal phase III study. We analyzed polysomnography data for daridorexant 25 and 50 mg, zolpidem 10 mg, and placebo groups. Polysomnography was conducted at baseline, then on Days 1/2, 15/16, and 28/29 in the phase II study, and Months 1 and 3 in the phase III study. The number, duration, and distribution of wake bouts (≥ 0.5 min) were assessed.
Data from 1111 patients (phase II study: daridorexant 50 mg [n = 61], zolpidem 10 mg [n = 60], placebo [n = 60]; phase III study: daridorexant 25 mg [n = 310], daridorexant 50 mg [n = 310], placebo [n = 310]) were analyzed. Long wake bouts were defined as > 6 min. Compared with placebo, daridorexant 50 mg reduced overall wake time (p < 0.05; all time points, both studies), the odds of experiencing long wake bouts (p < 0.001; Months 1 and 3, phase III study), and the cumulative duration of long wake bouts (p < 0.01; all time points, both studies). Reductions in long wake bouts were sustained through the second half of the night and correlated with improvements in daytime functioning. An increase in the cumulative duration of short wake bouts was observed with daridorexant 50 mg (p < 0.01 vs placebo, Months 1 and 3, phase III study); this was uncorrelated with daytime functioning.
Daridorexant reduced the number and duration of longer wake bouts throughout the night compared with placebo, corresponding with improved daytime functioning.
Clinicaltrials.gov NCT02839200 (registered July 20, 2016), NCT03545191 (registered June 4, 2018).
达理多雷克斯ant，一种双重食欲素受体拮抗剂，于 2022 年初获得批准，可减少睡眠后觉醒次数，而不会减少失眠患者的觉醒次数。本事后分析的目的是探讨达理多雷克斯ant 对夜间觉醒次数、持续时间和分布的影响，及其与日间功能的相关性。
在一项 2 期剂量发现研究中，1111 名患有失眠症的成年人被随机分为安慰剂、唑吡坦 10mg 或达理多雷克斯ant 5、10、25 或 50mg 1:1:1:1:1:1 组，以及安慰剂或达理多雷克斯ant 25 或 50mg 1:1:1 组在一项关键的 3 期研究中。我们分析了达理多雷克斯ant 25 和 50mg、唑吡坦 10mg 和安慰剂组的多导睡眠图数据。在 2 期研究中，多导睡眠图在基线、第 1/2 天、第 15/16 天和第 28/29 天进行，在 3 期研究中在第 1 个月和第 3 个月进行。评估了觉醒次数（≥0.5 分钟）、持续时间和分布。
来自 1111 名患者的数据（2 期研究：达理多雷克斯ant 50mg [n=61]、唑吡坦 10mg [n=60]、安慰剂 [n=60]；3 期研究：达理多雷克斯ant 25mg [n=310]、达理多雷克斯ant 50mg [n=310]、安慰剂 [n=310]）被分析。长觉醒被定义为>6 分钟。与安慰剂相比，达理多雷克斯ant 50mg 减少了总觉醒时间（p<0.05；所有时间点，两项研究），经历长觉醒的几率（p<0.001；第 1 和 3 个月，3 期研究），以及长觉醒的累积持续时间（p<0.01；所有时间点，两项研究）。夜间后半段的长觉醒减少持续存在，并与日间功能的改善相关。与安慰剂相比，达理多雷克斯ant 50mg 观察到短觉醒持续时间的累积持续时间增加（p<0.01，第 1 和 3 个月，3 期研究）；这与白天的功能无关。
与安慰剂相比，达理多雷克斯ant 减少了整个夜间更长觉醒次数和持续时间，与日间功能改善相对应。
Clinicaltrials.gov NCT02839200（2016 年 7 月 20 日注册），NCT03545191（2018 年 6 月 4 日注册）。
