Abstract Rationale AD109 is a combination of a novel antimuscarinic, aroxybutynin, and a selective norepinephrine reuptake inhibitor, atomoxetine that was evaluated in 2 randomized, placebo-controlled Phase 3 trials, SynAIRgy and LunAIRo. Across both studies, AD109 improved airway obstruction, oxygenation, and OSA severity in adults with OSA across all disease severity and a wide range of weight classes. Here, in prespecified exploratory analysis, the effect of AD109 versus placebo on snoring frequency was assessed. Methods Snoring was measured via tracheal piezoelectric snore sensor during polysomnography (PSG) at baseline and at week 26 in both trials. Snoring loudness was determined for each breath during sleep as the sound level increase in decibels (dB) relative to background breathing noise (calculated from a 60-minute window moving average). Snoring frequency was predefined as the proportion of breaths during sleep exhibiting loudness 20dB above background breathing sound. For inclusion in analysis, participants were required to have at least 15% of breaths with snoring at baseline, and a follow up on-treatment PSG at week 26 with snoring measurement. The proportion of breaths with snoring was compared between AD109 and placebo at week 26 using an ANCOVA model, adjusted for randomization strata and study as fixed effects and baseline snoring frequency as a covariate. Results PSG data with snoring measurement were available at both timepoints in N = 351 participants in the AD109 arm and N = 462 in the placebo arm. Of these, N = 189 (AD109) and N = 281 (Placebo) participants met baseline snoring criteria for inclusion. At baseline, the proportion of breaths with snoring in the AD109 arm (41.7 29.8, 60.2 % of breaths, median IQR) was similar to placebo (44.8 30.6, 62.3 % of breaths). AD109 reduced the proportion of breaths with snoring by 22.3 19.1, 25.5 % (Estimate 95%CI) vs a placebo reduction of 10.0 7.4,12.6% (difference: -12.3 -16.4, -8.2 %, p 0.001), Figure 1A. A majority (60.8%) of participants treated with AD109 exhibited a ≥ 50% reduction in the proportion of breaths with snoring, compared to 32.0% of those on placebo (p 0.001, Figure1B). Sensivitity analyses using higher thresholds for defining snoring (25dB and 30dB above background) showed similar results. Conclusions AD109 significantly reduces snoring frequency compared with placebo in patients with OSA. These findings indicate that AD109 may alleviate a key and socially disruptive symptom of OSA, complementing its effects on airway obstruction, oxygenation, and disease severity. This abstract is funded by: Apnimed, Inc.
Gell et al. (Fri,) studied this question.