Oveporexton for Narcolepsy Type 1 - Results from Two Phase 3 Trials.

Oveporexton (TAK-861), an oral orexin receptor 2-selective agonist, reduced symptoms of narcolepsy type 1 in a previous phase 2 trial.

Oveporexton (TAK-861)，一种口服的食欲素受体2选择性激动剂，在之前的2期试验中减少了发作性睡病1型的症状。

Methods

We conducted two phase 3, randomized, placebo-controlledtrials evaluating the efficacy and safety of oveporexton over a period of 12 weeks.

我们进行了两项为期12周的3期、随机、安慰剂对照试验，评估oveporexton的疗效和安全性。

Participants 16 to 70 years of age with narcolepsy type 1 were randomly assigned in a 3:3:2 ratio to receive twice-daily oveporexton (1 mg or 2 mg) or placebo in the First Light trial and in a 2:1 ratio to receive twice-daily oveporexton (2 mg) or placebo in the Radiant Light trial. The primary end point was the change from baseline to week 12 in mean sleep latency (the ability to stay awake under soporific conditions) on the Maintenance of Wakefulness Test (MWT; range, 0 to 40 minutes; normal, ≥20).

年龄在16至70岁之间的发作性睡病1型患者被随机分配，以3:3:2的比例在First Light试验中每天两次接受oveporexton（1毫克或2毫克）或安慰剂，以2:1的比例在Radiant Light试验中每天两次接受oveporexton（2毫克）或安慰剂。主要终点是从基线到第12周在维持觉醒测试（MWT；范围，0至40分钟；正常值≥20）上的平均睡眠潜伏期（在嗜睡条件下保持清醒的能力）的变化。

Key secondary end points included the change from baseline to week 12 in the Epworth Sleepiness Scale (ESS) total score (range, 0 to 24; normal, ≤10) and the weekly cataplexy rate at week 12.

关键次要终点包括从基线到第12周的Epworth嗜睡量表（ESS）总分（范围，0至24；正常值≤10）的变化，以及第12周的每周猝倒率。

Results

A total of 168 participants were enrolled in the First Light trial and 105 in the Radiant Light trial. Mean changes from baseline to week 12 in mean sleep latency on the MWT ranged from 14.3 to 19.8 minutes with oveporexton, as compared with -0.4 to -0.8 minutes with placebo (adjusted P<0.001 for all comparisons vs. placebo).

共有168名参与者参与了First Light试验，105名参与者参与了Radiant Light试验。从基线到第12周在MWT上的平均睡眠潜伏期的平均变化，oveporexton组为14.3至19.8分钟，而安慰剂组为-0.4至-0.8分钟（所有比较的调整后P<0.001，与安慰剂相比）。

Mean changes in the ESS total score ranged from -9.7 to -11.8 with oveporexton, as compared with -1.5 to -1.7 with placebo (adjusted P<0.001 for all comparisons vs. placebo).

在ESS总分的平均变化中，oveporexton组为-9.7至-11.8，而安慰剂组为-1.5至-1.7（所有比较的调整后P<0.001，与安慰剂相比）。

Median percent reductions in the weekly cataplexy rate ranged from 79.0 to 88.8% with oveporexton, as compared with 27.7 to 39.1% with placebo (adjusted P<0.001 for all comparisons vs. placebo).

每周猝倒率的中位百分比降低，oveporexton组为79.0至88.8%，而安慰剂组为27.7至39.1%（所有比较的调整后P<0.001，与安慰剂相比）。

Adverse events occurred in 86 to 89% of the participants with oveporexton, as compared with 43 to 54% with placebo; the most common adverse events were increased urinary frequency and transient insomnia, which occurred in a majority of participants receiving oveporexton.

在接受oveporexton治疗的参与者中，有86至89%的人出现了不良事件，而使用安慰剂的参与者中这一比例为43至54%；最常见的不良事件是尿频增加和短暂性失眠，这些在大多数接受oveporexton治疗的参与者中发生。

Conclusions

Over a period of 12 weeks, oveporexton significantly improved measures of wakefulness, sleepiness, and cataplexy in participants with narcolepsy type 1.

在为期12周的研究中，oveporexton显著改善了1型嗜睡症患者的清醒度、嗜睡和猝倒的测量指标。

Increased urinary frequency and transient insomnia were common side effects.

尿频增加和短暂性失眠是常见的副作用。

(Funded by Takeda Development Center Americas; the First Light and Radiant Light ClinicalTrials.gov numbers, NCT06470828 and NCT06505031.).

该研究由武田开发中心美洲资助；First Light和Radiant Light的临床试验注册号分别为NCT06470828和NCT06505031。