The oral agent AD109 is superior to placebo in reducing the severity of obstructive sleep apnea (OSA), according to study results presented at the 2023 Annual Meeting of the American Academy of Sleep Medicine and the Sleep Research Society, held from June 3 to 7 in Indianapolis, Indiana.
Currently, there is no approved pharmacotherapy for OSA; but, the combination of noradrenergic and antimuscarinic drugs has shown promising results. AD109 is a therapeutic formulation combining atomoxetine, a norepinephrine reuptake inhibitor, with aroxybutynin, an antimuscarinic agent that has proven to be effective in a 1-night treatment in patients with mild OSA. The safety and efficacy of AD109 for a longer treatment duration in patients with severe OSA is not clear.
For the study, researchers sought to assess the efficacy, safety, and tolerability of 2 different doses of AD109 (75/2.5 mg and 75/5 mg) as well as atomoxetine 75mg alone, vs a placebo.
The researchers conducted the Mariposa study across 25 centers and utilized a randomized, controlled, parallel arms design. Participant eligibility included a confirmed diagnosis of OSA with an apnea-hypopnea index (AHI4, 4% desaturation definition for hypopneas) between 10 and 45. In total, 211 patients (41% women; median age, 55 years [interquartile range, 48-60]) were enrolled in this study, with 41% women. The median body mass index (BMI) was 32.2 kg/m2 (IQR, 28.0-35.2 kg/m2).
In the group receiving the 75/2.5 mg dose, AHI4 was reduced from an initial value of 20.5 (IQR, 12.3-27.2) to 10.8 (IQR, 5.6-18.5). Similarly, in the group receiving the AD109 75/5 mg dose, AHI4 was reduced from 19.4 (IQR, 13.7-26.4) to 9.5 (IQR, 6.1-19.3). The reductions observed in both dose arms were statistically significant (P <.0001) when compared with the placebo group.
With atomoxetine alone, AHI4 decreased from 19.0 (IQR, 11.8-28.8) to 11.8 (IQR, 5.5-21.5). This decline was found to be statistically significant (P <.01), compared with the placebo group. The placebo group experienced a decline in AHI from 20.1 (IQR, 11.9-25.9) to 16.3 (IQR, 11.1-28.9).
In total, 44% of study participants experienced an AHI4 reduction of over 50% from their baseline when receiving either dose of AD109. Patient-reported outcome questionnaires (PROMIS) reported an improvement in fatigue scores among patients treated with AD109 75/2.5 mg dose (p< 0.05 vs placebo and atomoxetine alone). While atomoxetine alone effectively improved AHI4, it led to a reduction of more than 20 minutes in total sleep time compared with both placebo and AD109 (P < .05).
No severe adverse events were reported in patients receiving AD109, with the most frequently encountered side effects being dry mouth, insomnia, and nausea.
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Ojile J, Schweitzer P, Thein S, et al. Mariposa: Oral therapy AD109 improves objective & patient reported outcomes in OSA. Randomized, placebo controlled clinical trial. Abstract presented at: SLEEP 2023; June 3-7, 2023; Indianapolis, IN. Abstract 0538.