S1E53 | SynAIRgy: The First Pill for Sleep Apnea? A Phase 3 Trial of AD109

Could a bedtime pill become a meaningful treatment for obstructive sleep apnea?In PRISM Rounds Season 1, Episode 53, we examine “Aroxybutynin and atomoxetine (AD109) for obstructive sleep apnea: a randomized phase 3 trial (SynAIRgy).”This randomized, double-blind, placebo-controlled trial evaluated AD109, an investigational combination of aroxybutynin and atomoxetine, in adults with obstructive sleep apnea who could not or would not use positive airway pressure therapy.AD109 improved the apnea-hypopnea index and measures of oxygenation over 26 weeks. However, the average placebo-adjusted reduction was four respiratory events per hour, fatigue did not significantly improve compared with placebo, and approximately one in five participants discontinued treatment because of adverse effects.We discuss:• How AD109 is intended to improve upper-airway muscle function• The trial design and primary findings• Relative versus absolute reductions in the apnea-hypopnea index• Intention-to-treat versus on-treatment results• Hypoxic burden and changes in sleep architecture• Insomnia, dry mouth, tachycardia, and treatment discontinuation• Which patients might benefit if AD109 is approved• Why CPAP remains the most effective and best-established treatment for most patientsDoes SynAIRgy represent the beginning of oral precision therapy for sleep apnea, and can better phenotyping identify patients whose benefits outweigh the adverse effects?Primary article: https://doi.org/10.1093/ajrccm/aamag215Accompanying editorial: https://doi.org/10.1093/ajrccm/aamag243PRISM Rounds is intended for education and discussion and does not provide medical advice.Tags: PRISM Rounds, SynAIRgy, AD109, aroxybutynin, atomoxetine, obstructive sleep apnea, OSA, sleep apnea treatment, sleep medicine, CPAP, positive airway pressure, apnea-hypopnea index, AHI, hypoxic burden, randomized clinical trial, phase 3 trial, AJRCCM, pulmonary medicine, clinical research, medical education, FOAMed#PRISMRounds #SynAIRgy #AD109 #SleepApnea #OSA #SleepMedicine #CPAP #ClinicalTrials #PulmonaryMedicine #MedicalEducation #FOAMed