Aroxybutynin and atomoxetine (AD109) for obstructive sleep apnea: a randomized phase 3 trial (SynAIRgy).

AD109 (investigational fixed-dose oral combination of aroxybutynin 2.5 mg/atomoxetine 75 mg) is designed to target neuromuscular dysfunction in OSA.

AD109（正在研究的固定剂量口服组合药物，包含2.5毫克的阿罗布托林和75毫克的托莫西汀）旨在针对OSA中的神经肌肉功能障碍。

Background

To evaluate the efficacy/safety of AD109 over 6 months in a diverse OSA population unable to use PAP.

评估AD109在6个月内对无法使用PAP的多样化OSA人群的疗效/安全性。

Methods

SynAIRgy enrolled adults with mild-to-severe OSA who were intolerant to or refused PAP therapy into a randomized, double-blind, placebo-controlled, 26-week parallel-arm trial of AD109 vs placebo across 69 centers.

SynAIRgy项目招募了对PAP治疗不耐受或拒绝接受PAP治疗的轻度至重度OSA成人患者，参与了一项为期26周的随机、双盲、安慰剂对照的平行组试验，比较AD109与安慰剂的效果，在69个中心进行。

The primary efficacy endpoint was change from baseline to week 26 in apnea-hypopnea index (AHI).

主要疗效终点是从基线到第26周呼吸暂停低通气指数（AHI）的变化。

Key secondary endpoints were oxygen desaturation index (ODI), Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue T-score, hypoxic burden (HB), PROMIS-Sleep Impairment T-score, and proportion of participants with ≥50% AHI reduction.

关键次要终点包括氧减指数（ODI）、患者报告的结果测量信息系统（PROMIS）-疲劳T得分、缺氧负荷（HB）、PROMIS-睡眠障碍T得分以及AHI减少≥50%的参与者比例。

measurements_and_main_results

A total of 646 eligible participants (median age 58 years, 49.3% female, median body mass index 32.4 kg/m2) were randomized.

共有646名符合条件的参与者（中位年龄58岁，49.3%为女性，中位体重指数为32.4 kg/m2）被随机分配。

Median baseline AHI was 19.6 events/hour with 35% mild, 42% moderate, and 23% severe OSA.

基线时的平均呼吸暂停低通气指数（AHI）中位数为每小时19.6次事件，其中35%为轻度，42%为中度，23%为重度OSA。

At week 26, mean AHI treatment difference was -4.0 events/hour (95% CI, -6.4 to -1.6; P = .001), representing a model-estimated 44.1% vs 17.6% decrease from baseline (P <.0001).

在第26周，平均AHI治疗差异为-4.0次/小时（95%置信区间，-6.4至-1.6；P=0.001），代表从基线开始的模型估计减少44.1%与17.6%（P<0.0001）。

AD109 demonstrated improvements in ODI and HB at week 26 vs placebo; however, no statistically significant difference was observed for PROMIS-Fatigue.

AD109在第26周与安慰剂相比，在ODI和HB方面显示出改善；然而，对于PROMIS-Fatigue没有观察到统计学上的显著差异。

Overall, 21.2% of participants on AD109 and 3.1% on placebo discontinued therapy due to adverse events.

总体而言，21.2%的AD109参与者和3.1%的安慰剂参与者因不良事件而停药。

The most common adverse events with AD109 were dry mouth, nausea, insomnia, and urinary hesitation, with no serious treatment-related adverse events.

AD109最常见的不良事件包括口干、恶心、失眠和尿潴留，但没有与治疗相关的严重不良事件。

Conclusions

AD109 significantly improved airway obstruction and oxygenation at 26 weeks across a broad range of patients unable to use PAP, suggesting that AD109 could become a potential treatment option for patients with OSA.

AD109在26周时显著改善了无法使用PAP的广泛患者群体的气道阻塞和氧合情况，表明AD109可能成为OSA患者的潜在治疗选择。

clinical_trial_registration

www.clinicaltrials.gov (NCT05813275 [SynAIRgy]).

www.clinicaltrials.gov (NCT05813275 [SynAIRgy]).