J Clin Sleep Med. 2022 Aug 17. doi: 10.5664/jcsm.10250. Online ahead of print.
ABSTRACT
STUDY OBJECTIVE: Obstructive sleep apnea (OSA) is a common and serious sleep disorder whose treatment remains challenging due to lack of adherence to approved therapies. Previous pharmacological studies addressing sleep-related upper airway muscle hypotonia suggested that the combination of atomoxetine and oxybutynin is effective in treating OSA. The current study is with aroxybutynin (AD109), a new enantiomerically pure form of oxybutynin with better safety profile compared to racemic oxybutynin.
METHODS: This was a randomized, double-blind, placebo-controlled, crossover study in patients with mild to moderate OSA. Each received low-dose AD109 (37.5/2.5mg), high-dose (75/2.5mg), and placebo at bedtime across three overnight periods in a randomized order. Adverse events were collected by telephone contact with participants during each washout period. The primary endpoint was change in Hypoxic Burden (HB) and secondary endpoint was apnea-hypopnea index (AHI).
RESULTS: Patients treated with both the high and low doses of AD109 had a statistically significant and clinically meaningful difference from placebo in HB. Median[IQR] HB for participants on placebo was 13.9[4.5-21.9]%min/h vs 2.3[0.1-10.5]%min/h for patients on the high dose (p<0.001) and to 7.3[2-12.5]%min/h on the low dose (p<0.01). AHI went from a median of 13.2[8.0-19.1] events/h on placebo reduced to 5.5[2.2 to 9.6] events/h on the high dose (p<0.001) and to 7.8[4-13.7] on the low dose (p<0.05). AD109 demonstrated a favorable safety profile.
CONCLUSIONS: This study provides further support that a pharmacological intervention for OSA, namely the combination of atomoxetine and aroxybutynin, offers promising results. Additional development of this compound and others is warranted.
CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Identifier: NCT04631107; Title: AD109 Dose Finding in Mild to Moderate OSA; URL: https://clinicaltrials.gov/ct2/show/NCT04631107.
PMID:35975547 | DOI:10.5664/jcsm.10250
