Evidence map›Paper›PMID 42148495›Full record

Trial reportAmerican journal of respiratory and critical care medicine2026

Aroxybutynin and atomoxetine (AD109) for obstructive sleep apnea: a randomized phase 3 trial (SynAIRgy).

Patrick J Strollo, Ron Farkas, Luigi Taranto-Montemurro, John Cronin, Sanjay R Patel, SynAIRgy Investigators

Registry-linked trialAbstract readRandomized Controlled TrialClinical Trial, Phase IIIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in American journal of respiratory and critical care medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05813275 (Phase 3 Randomized Double-Blind Placebo-Controlled 6-month Parallel-Arm Study to Compare a Fixed Dose Combination of Aroxybutynin/Atomoxetine), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

NCT05813275 phase3completednot on this map

Phase 3 Randomized Double-Blind Placebo-Controlled 6-month Parallel-Arm Study to Compare a Fixed Dose Combination of Aroxybutynin/Atomoxetine (AD109) to Placebo in Obstructive Sleep Apnea (SynAIRgy Study)

TypeinterventionalSponsorApnimedRan2023 to 2025Enrolled646ConditionsOSAArmsAD109, Placebo
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Current Updates on Pharmacotherapy for Obstructive Sleep Apnea.Journal of rhinology : official journal of the Korean Rhinologic Society · 2026
    Review
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Patrick J StrolloDepartment of Medicine Service, Veteran Affairs Pittsburgh Healthcare System, Pittsburgh, PA, United States.
Ron FarkasApnimed, Inc., Cambridge, MA, United States.
Luigi Taranto-MontemurroApnimed, Inc., Cambridge, MA, United States.
John CroninApnimed, Inc., Cambridge, MA, United States.
Sanjay R PatelDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, United States.ORCID 0000-0002-9142-5172
SynAIRgy Investigators

Funding

Apnimed, IncApnimed, Inc.
6 · The paper itself

Abstract

rationaleMany patients with obstructive sleep apnea (OSA) are unable to tolerate long-term positive airway pressure (PAP) therapy, highlighting the need for alternative treatments. AD109 (investigational fixed-dose oral combination of aroxybutynin 2.5 mg/atomoxetine 75 mg) is designed to target neuromuscular dysfunction in OSA.

objectivesTo evaluate the efficacy/safety of AD109 over 6 months in a diverse OSA population unable to use PAP.

methodsSynAIRgy enrolled adults with mild-to-severe OSA who were intolerant to or refused PAP therapy into a randomized, double-blind, placebo-controlled, 26-week parallel-arm trial of AD109 vs placebo across 69 centers. The primary efficacy endpoint was change from baseline to week 26 in apnea-hypopnea index (AHI). Key secondary endpoints were oxygen desaturation index (ODI), Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue T-score, hypoxic burden (HB), PROMIS-Sleep Impairment T-score, and proportion of participants with  ≥50% AHI reduction. MEASUREMENTS AND MAIN

resultsA total of 646 eligible participants (median age 58 years, 49.3% female, median body mass index 32.4 kg/m2) were randomized. Median baseline AHI was 19.6 events/hour with 35% mild, 42% moderate, and 23% severe OSA. At week 26, mean AHI treatment difference was -4.0 events/hour (95% CI, -6.4 to -1.6; P = .001), representing a model-estimated 44.1% vs 17.6% decrease from baseline (P <.0001). AD109 demonstrated improvements in ODI and HB at week 26 vs placebo; however, no statistically significant difference was observed for PROMIS-Fatigue. Overall, 21.2% of participants on AD109 and 3.1% on placebo discontinued therapy due to adverse events. The most common adverse events with AD109 were dry mouth, nausea, insomnia, and urinary hesitation, with no serious treatment-related adverse events.

conclusionsAD109 significantly improved airway obstruction and oxygenation at 26 weeks across a broad range of patients unable to use PAP, suggesting that AD109 could become a potential treatment option for patients with OSA. CLINICAL

trial registrationwww.clinicaltrials.gov (NCT05813275 [SynAIRgy]).

Indexed as

Adrenergic Uptake InhibitorsAtomoxetine HydrochlorideMandelic AcidsSleep Apnea, ObstructiveAdultAgedDouble-Blind MethodDrug CombinationsFemaleHumansMaleMiddle AgedPolysomnographyTreatment OutcomeAdrenergic Uptake InhibitorsAtomoxetine HydrochlorideDrug CombinationsMandelic Acidsoxybutyninairway obstructionhypoxiapatient-reported outcome measures

Identifiers

PMID42148495
PMCPMC13318230

What Socratic holds

Textmetadata
LicenceCC BY
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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.