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Clinical trials

AHI changed by -3.88 events per hour on AD109 and 0.21 on placebo in sleep apnea at 6 months

In the Phase 3 LunAIRo trial of 650 analyzed adults with obstructive sleep apnea, the apnea-hypopnea index changed by -3.88 events per hour on AD109 and 0.21 on placebo at 6 months. The record lists full results and safety tables.

By The Priority Review desk

Machine-summarized from the primary sources listed below; not independently reported. How we use automation

In Apnimed's Phase 3 LunAIRo trial, the average change in apnea-hypopnea index at 6 months was -3.88 events per hour in the 324 adults on AD109 and 0.21 in the 326 adults on placebo, the study record shows. The record gives a least squares mean difference of -4.08 (95% confidence interval -6.14 to -2.03) and a p-value under 0.001. A 660-participant, one-year trial in adults with intolerance of positive airway pressure or a current refusal of it now has posted outcome and safety data.

Change in apnea-hypopnea index at 6 months AD109 and placebo in two analyses, with 95% confidence intervals -8 -6 -4 -2 0 2 4 Events per hour, change from baseline AD109 treatment policy (n = 324) -5.37 to -2.39 -3.88 Placebo treatment policy (n = 326) -1.24 to 1.65 0.21 AD109 while on treatment (n = 240) -7.51 to -4.15 -5.83 Placebo while on treatment (n = 293) -1.55 to 1.50 -0.02 Treatment policy difference: -4.08 (95% confidence interval -6.14 to -2.03), p-value under 0.001. While-on-treatment difference: -5.81 (-8.07 to -3.55), p-value under 0.0001. From the trial registry record NCT05811247, results first submitted October 13, 2026. The Priority Review.
Change in apnea-hypopnea index at 6 months AD109 and placebo in two analyses, with 95% confidence intervals -8 -6 -4 -2 0 2 4 Events per hour, change from baseline AD109 treatment policy (n = 324) -5.37 to -2.39 -3.88 Placebo treatment policy (n = 326) -1.24 to 1.65 0.21 AD109 while on treatment (n = 240) -7.51 to -4.15 -5.83 Placebo while on treatment (n = 293) -1.55 to 1.50 -0.02 Treatment policy difference: -4.08 (95% confidence interval -6.14 to -2.03), p-value under 0.001. While-on-treatment difference: -5.81 (-8.07 to -3.55), p-value under 0.0001. From the trial registry record NCT05811247, results first submitted October 13, 2026. The Priority Review.

Why it matters

The record's brief summary says the study compares a fixed dose combination of AD109 with placebo in obstructive sleep apnea. The record names the combination as aroxybutynin and atomoxetine. Its eligibility criteria require adults 18 years or older with an apnea-hypopnea index above 5 and either intolerance of positive airway pressure or a current refusal of it. The record lists no results before this posting.

Primary outcome at 6 months

Results were first submitted on October 13, 2026. The primary outcome is the change from baseline in apnea-hypopnea index at 6 months, measured by polysomnography. The record reports it in two analyses.

  • Treatment policy estimand, full analysis set: -3.88 events per hour on AD109 (95% confidence interval -5.37 to -2.39, 324 participants) and 0.21 on placebo (-1.24 to 1.65, 326 participants). The difference is -4.08 (-6.14 to -2.03), p-value under 0.001.
  • While-on-treatment estimand: -5.83 events per hour on AD109 (-7.51 to -4.15, 240 participants) and -0.02 on placebo (-1.55 to 1.50, 293 participants). The difference is -5.81 (-8.07 to -3.55), p-value under 0.0001.

Both analyses used a mixed model for repeated measures with a superiority test. The record says the full analysis set holds all randomized participants who received at least one dose, without participants from terminated site 1308. The while-on-treatment group also required at least one post-baseline on-treatment polysomnography.

Trial size and participants

LunAIRo is a randomized, parallel-arm, quadruple-masked Phase 3 study. The record lists an actual enrollment of 660, with 329 participants started on AD109 and 331 on placebo. The study began on August 28, 2023, and the record shows a completion date of May 7, 2025.

The AD109 tablet held aroxybutynin 2.5 mg and atomoxetine 75 mg, taken once daily at bedtime in Weeks 2 to 51. Week 1 was a run-in at atomoxetine 37.5 mg. The placebo arm took a matching tablet for 51 weeks.

In the 650 participants in the baseline table, the mean age was 57.2 years on AD109 and 57.4 on placebo. There were 160 women and 164 men on AD109, and 138 women and 188 men on placebo. The mean baseline apnea-hypopnea index was 24.03 events per hour on AD109 and 24.69 on placebo. Baseline groups split into 244 participants below 15, 213 from 15 to 30 and 193 above 30.

The record lists sites in states including Alabama, California, Ohio and Texas.

Participant flow

In the participant flow, 250 of 329 participants on AD109 completed the study, against 274 of 331 on placebo. The record lists the reasons for leaving, on AD109 and placebo in order:

  • Adverse event: 12 and 7
  • Lost to follow-up: 24 and 20
  • Physician decision: 2 and 7
  • Withdrawal by subject: 33 and 19
  • Site terminated by sponsor: 3 and 2
  • Other or not reported: 5 and 2

Safety measures

The safety population was 328 participants on AD109 and 327 on placebo, up to 53 weeks. The record reports 0 deaths in either arm. Adverse events classed as serious affected 5 participants on AD109 and 10 on placebo. Other adverse events at or above the 5% reporting threshold affected 220 participants on AD109 and 122 on placebo.

Among the events the record lists, selected here with participants on AD109 against placebo:

  • Dry mouth: 130 and 31
  • Nausea: 43 and 7
  • Middle insomnia: 44 and 13
  • Initial insomnia: 32 and 12
  • Dyspepsia: 20 and 7
  • Constipation: 19 and 8

The record lists ischaemic stroke and a suicide attempt among the serious events on placebo, each classified as possibly related to study intervention. It lists one road traffic accident and one intracranial aneurysm among those on AD109, each classified as not related.

Sources