A randomized controlled clinical trial depicted significant improvements in the severity of obstructive sleep apnea among patients with varying levels of apnea-hypopnea index (AHI4) with the use of a combination of the norepinephrine reuptake inhibitor Atomoxetine and the antimuscarinic Aroxybutynin (AD109) over a four-week treatment period. Joseph Ojile et al. sought to assess the tolerability, safety, and effectiveness of two different doses of AD109 (75/2.5 mg and 75/5 mg) and 75 mg Atomoxetine (monotherapy) when administered over four weeks in patients with obstructive sleep apnea.

The trial enrolled patients with obstructive sleep apnea and AHI4 ranging from 10 to 45 (defined as a 4% desaturation for hypopneas). The primary focus of the study was to determine the impact of AD109 compared to placebo on the alteration in AHI4. Additionally, exploratory outcomes included the assessment of patient-reported outcome questionnaires (PROMIS). Overall, 211 volunteers were included in the trial, with 41% of them being female.

The median age was 55 years (with an interquartile range of 48-60), and the BMI was 32.2 kg/m² (with an interquartile range of 28.0-35.2). In the AD109 treatment groups, the AHI4 significantly decreased from a baseline of 20.5 (12.3-27.2) to 10.8 (5.6-18.5) in the 75/2.5 mg dose arm and from 19.4 (13.7-26.4) to 9.5 (6.1-19.3) in the 75/5 mg dose arm. For patients receiving Atomoxetine alone, the AHI4 decreased from 19.0 (11.8-28.8) to 11.8 (5.5-21.5), while the placebo group showed a decrease from 20.1 (11.9-25.9) to 16.3 (11.1-28.9).

As found, 44% of the subjects administered with AD109 experienced a decline in AHI4 higher than 50% from baseline. Notably, patients receiving AD109 75/2.5 mg showed an enhancement in PROMIS fatigue scores. However, Atomoxetine alone resulted in a decrease of higher than 20 minutes in total sleep time in comparison with placebo and AD109. No serious side effects were noted with AD109. Nausea, insomnia, and dry mouth were the most common side effects reported.

Over a four-week treatment period, AD109 demonstrated both objective and subjective improvements in the severity of obstructive sleep apnea among a diverse group of patients with varying levels of AHI4. The findings from the Mariposa trial play a pivotal role in shaping the design of phase 3 trials for AD109 in the treatment of obstructive sleep apnea.