Trial reportJournal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine2022
Combination of atomoxetine with the novel antimuscarinic aroxybutynin improves mild to moderate OSA.
Trial report in Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 27 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase 2 Randomized Double-Blind Placebo-Controlled 3-Period Single-Dose Crossover Study to Evaluate the Safety and Efficacy of Two Doses of AD-109 in Mild to Moderate Obstructive Sleep Apnea
Comparative Effectiveness of Positive Airway Pressure Therapy, Dental Device, and Atomoxetine-Oxybutynin for Sleep Apnea: the ADAPT-OSA Study
Who cites it
27 citing papers in PubMed, 4 syntheses or guidelines pooled it, 35 citations in OpenAlex.
- Are noradrenergics combined with antimuscarinics the future pharmacologic treatment for obstructive sleep apnea? A systematic review and meta-analysis of randomized controlled trials.Sleep & breathing = Schlaf & Atmung · 2024Pooled it
- Effect of norepinephrine reuptake inhibitors combined with antimuscarinic agents vs monotherapy for OSA: a systematic review and meta-analysis.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2024Pooled it
- The Hypoxic Burden, Clinical Implication of a New Biomarker in the Cardiovascular Management of Sleep Apnea Patients: A Systematic Review.Reviews in cardiovascular medicine · 2024Pooled it
- Pharmacological treatment for obstructive sleep apnea: A systematic review and meta-analysis.Clinics (Sao Paulo, Brazil) · 2024Pooled it
- Aroxybutynin and atomoxetine (AD109) for obstructive sleep apnea: a randomized phase 3 trial (SynAIRgy).American journal of respiratory and critical care medicine · 2026Trial
- Atomoxetine plus oxybutynin for symptomatic snoring and airflow limitation in individuals without moderate-to-severe obstructive sleep apnea.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2025Trial
- Effect of viloxazine and trazodone in obstructive sleep apnoea: a randomised, placebo-controlled, cross-over study.Thorax · 2025Trial
- Effects of the Combination of Pimavanserin and Atomoxetine on OSA Severity: A Randomized Crossover Trial.Chest · 2025Trial
- 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 · 2023Trial
- The combination of atomoxetine and oxybutynin for the treatment of obstructive sleep apnea in children with Down syndrome.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2023Trial
- Targeting Hypoglossal Neurobiology in the Treatment of Obstructive Sleep Apnea: The Emergence of Aroxybutynin-Atomoxetine (AD109).Brain sciences · 2026Article
- Mechanisms of upper airway muscle control in sleep reveal therapeutic targets for obstructive sleep apnea.American journal of respiratory cell and molecular biology · 2026Review
- Obstructive Sleep Apneas and Cardiovascular Diseases.Clocks & sleep · 2026Review
- Review
- Aroxybutynin and atomoxetine (AD109) for the treatment of obstructive sleep apnea: Rationale, design and baseline characteristics of the phase 3 clinical trials.Contemporary clinical trials communications · 2025Article
- Fatigue is distinct from sleepiness and negatively impacts individuals living with obstructive sleep apnea (OSA): results from qualitative research of individuals with OSA.Health and quality of life outcomes · 2025Article
- The effect of continuous positive airway pressure therapy on atrial fibrillation in patients with obstructive sleep apnea.Frontiers in medicine · 2025Review
- Efficacy of atomoxetine and oxybutynin in the treatment of pediatric obstructive sleep apnea, a three case report.Frontiers in sleep · 2025Article
- Tackling obstructive sleep apnea with pharmacotherapeutics: expert guidance.Expert opinion on pharmacotherapy · 2024Review
- Reply to: Combination of Aroxybutynin and Atomoxetine in Obstructive Sleep Apnea: Is the Effect One Plus One Greater Than Two?American journal of respiratory and critical care medicine · 2024Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
STUDY
objectiveObstructive sleep apnea is a common and serious sleep disorder for which 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 obstructive sleep apnea. The current study is with aroxybutynin (AD109), a new enantiomerically pure form of oxybutynin with better safety profile compared to racemic oxybutynin.
methodsThis was a randomized, double-blind, placebo-controlled, crossover study in patients with mild to moderate obstructive sleep apnea. Each received low-dose AD109 (37.5/2.5 mg), high-dose AD109 (75/2.5 mg), and placebo at bedtime across 3 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 and secondary endpoint was apnea-hypopnea index.
resultsPatients treated with both the high and low doses of AD109 had a statistically significant and clinically meaningful difference from placebo in hypoxic burden. Median [interquartile range] hypoxic burden 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 (
conclusionsThis study provides additional support that a pharmacological intervention for obstructive sleep apnea, namely the combination of atomoxetine and aroxybutynin, offers promising results. Additional development of this compound and others is warranted. CLINICAL
trial registrationRegistry: ClinicalTrials.gov; Name: AD109 Dose Finding in Mild to Moderate OSA; URL: https://clinicaltrials.gov/ct2/show/NCT04631107; Identifier: NCT04631107. CITATION: Rosenberg R, Abaluck B, Thein S. Combination of atomoxetine with the novel antimuscarinic aroxybutynin improves mild to moderate OSA.
Indexed as
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.