A recent Phase II clinical trial has unveiled promising results for the treatment of obstructive sleep apnea (OSA) with AD109, a novel combination medication comprising aroxybutynin, an antimuscarinic agent, and atomoxetine, a norepinephrine reuptake inhibitor. This study was published in the American Journal Of Respiratory And Critical Care Medicine by Paula K. and colleagues.

This randomized, double-blind, placebo-controlled study, spanning four weeks and involving 211 participants, evaluated the efficacy and safety of AD109 in comparison with atomoxetine alone and placebo. Patients were assessed using polysomnograms to gauge sleep parameters, with the primary outcome being the reduction in the apnea–hypopnea index (AHI) with a 4% desaturation criterion, a key indicator of OSA severity.

The results demonstrated compelling improvements in sleep-related metrics:
Reduction in AHI: The AD109 2.5/75 mg arm showcased a remarkable decrease from a median AHI of 20.5 to 10.8 (−47.1%), while the AD109 5/75 mg arm exhibited a reduction from 19.4 to 9.5 (−42.9%). Notably, both AD109 doses significantly outperformed placebo (P < 0.0001). The atomoxetine alone group also demonstrated a meaningful decrease from 19.0 to 11.8 (−38.8%; P < 0.01 vs. placebo).

Subjective Improvements: Participants reported significant fatigue improvement with AD109 2.5/75 mg (P < 0.05 vs. placebo and atomoxetine). However, atomoxetine alone was associated with reduced total sleep time (P < 0.05 vs. AD109 and placebo).

The safety profile of AD109 was favorable, with the most common adverse events including dry mouth, insomnia, and urinary hesitancy. The study's findings suggest that AD109 could offer clinically meaningful benefits for individuals with OSA, warranting further investigation and development of this compound as a potential pharmacotherapy for OSA. The novel combination of aroxybutynin and atomoxetine has shown promise in addressing OSA symptoms, potentially providing a new avenue for patients who struggle with conventional treatments like continuous positive airway pressure (CPAP).

Reference:
Schweitzer, P. K., Taranto-Montemurro, L., Ojile, J. M., Thein, S. G., Drake, C. L., Rosenberg, R., Corser, B., Abaluck, B., Sangal, R. B., & Maynard, J. The combination of aroxybutynin and atomoxetine in the treatment of obstructive sleep apnea (MARIPOSA): A randomized controlled trial. American Journal of Respiratory and Critical Care Medicine,2023;208(12):1316–1327. https://doi.org/10.1164/rccm.202306-1036oc