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Abstract Introduction There are no FDA-approved drugs available for the treatment of obstructive sleep apnea (OSA). The relaxation of upper airway muscles at sleep onset and insufficient muscle reactivation during obstructive events are the key pathophysiological determinants of OSA. Pharmacotherapy targeting the activation of upper airway muscles is a promising strategy for the alleviation of OSA. Methods AD109 is a combination of the antimuscarinic aroxybutynin 2.5 mg, the R-enantiomer of oxybutynin, and the norepinephrine reuptake inhibitor atomoxetine 75 mg. In the phase 2b Mariposa trial, AD109 demonstrated a clinically significant reduction of -47.1% (95% CI: -61.2 to -27.9) in the apnea-hypopnea index (AHI) compared to a placebo, along with an important decrease in subjective fatigue, measured using the Patient Reported Outcome Measurement Information System (PROMIS) scale, at one month of treatment. The ongoing SYNAIRGY study, a placebo-controlled 26-week phase 3 clinical trial, is designed to investigate both the efficacy and safety of AD109 2.5/75 for the treatment of mild to severe OSA. Eligible participants include adults with AHI4 (4% desaturation definition for hypopneas) ≥5, and a BMI 42kg/m2 for women and 40 kg/m2 for men who either decline or are unable to tolerate continuous positive airway pressure treatment. Approximately 640 participants will be randomized in a 1:1 ratio to receive either placebo or AD109. We hypothesize that AD109 treatment will provide a clinically meaningful AHI decrease compared to placebo-treated participants with OSA. Results The primary endpoint is the response rate in the AD109 arm vs. placebo arm, where response is defined as 50% reduction in AHI4 from baseline to 26-week polysomnogram (PSG). Participants will have a PSG on treatment at week 4. Secondary endpoints include changes from baseline in PROMIS-Fatigue, PROMIS-Sleep Impairment, hypoxic burden, Patient Global Impression of Severity (PGI-S) for fatigue, and the Epworth Sleepiness Scale. Safety assessments will include multiple in-office measurements of heart rate and blood pressure throughout the treatment period. Conclusion The SynAIRgy phase 3 randomized, controlled clinical trial aims to assess the efficacy and safety of AD109 in in the treatment of OSA by targeting key pathophysiologic mechanisms of upper airway muscle relaxation during sleep. Support (if any) Apnimed
Strollo et al. (Sat,) studied this question.