0679 Aroxybutynin and Atomoxetine (AD109) and Patient-Reported Outcomes: A Pooled Analysis of the SynAIRgy and LunAIRo Trials in Obstructive Sleep Apnea

Abstract Introduction Symptom burden in obstructive sleep apnea (OSA) varies widely among patients. AD109 is an investigational oral anti-apneic neuromuscular modulator that combines in one tablet the novel antimuscarinic, aroxybutynin (2.5 mg), with the selective norepinephrine reuptake inhibitor, atomoxetine (75 mg). AD109 significantly improved objective measures of airway obstruction and oxygenation vs placebo (PBO) in two phase 3 clinical trials in OSA. This analysis focuses on change in patient-reported symptoms—including fatigue, sleep impairment, and daytime sleepiness—observed across both trials. Methods SynAIRgy (NCT05813275; N=646) and LunAIRo (NCT05811247; N=660) were randomized, double-blind, PBO-controlled, parallel-arm phase 3 trials of AD109 vs PBO in adults with mild-to-severe OSA (AHI >5) intolerant to or refusing positive airway pressure therapy. Patient reported outcomes (PROs) at Week 26 included the Patient Reported Outcome Measurement Information System (PROMIS)-Fatigue (F) T-score, PROMIS-Sleep Impairment (SI) T-score, and Epworth Sleepiness Scale (ESS). Pooled analyses were performed comparing change from baseline according to the on-treatment estimand, including all randomized participants who received ≥1 dose of study medication and had ≥1 post-baseline on-treatment polysomnogram. The integrated PRO analysis was also performed in participants with baseline excessive daytime sleepiness (ESS≥10). Results In the pooled analysis of PROs utilizing the on-treatment estimand (AD109: n=500; PBO: n=589), results (LS mean difference [SE]) numerically favored AD109 over PBO in PROMIS-F T-score (−0.48 [0.43]; P=0.27), PROMIS-SI T-score (−0.54 [0.48]; P=0.26) and ESS (= −0.18 [0.21]; P=0.4) at Week 26. A higher proportion of participants receiving AD109 achieved ≥3 point improvement in ESS at Week 26 relative to PBO (48.2% vs 41.6%; P=0.018). In participants with baseline excessive daytime sleepiness (AD109: n=280; PBO: n=294), AD109 significantly improved PROMIS-F and PROMIS-SI T-scores (LS mean±SE) at Week 26 by −8.8±0.4 and −9.9±0.5 points, respectively (vs −7.2±0.4 and −8.2±0.5 with PBO; P=0.007 and P=0.01). Similarly, AD109 significantly improved ESS (LS mean ± SE) at Week 26 by −4.5±0.2 points in participants having baseline excessive daytime sleepiness (vs −3.9±0.2 with PBO; P=0.04). Conclusion AD109 significantly improved patient-reported fatigue and sleepiness in participants with OSA, particularly those with defined sleepiness. Support (if any) These studies were supported by Apnimed, Inc.