Background: A recent multi-centric clinical trial, MARIPOSA, examined efficacy, safety and tolerability of AD109, a combination of atomoxetine and aroxybutynin vs. placebo and atomoxetine alone for treatment of sleep apnea. After a 4-week administration, AD109 substantially reduced the apnea hypopnea index (AHI4, 4% desaturation definition for hypopneas) vs. placebo and Patient Reported Outcome Questionnaires (PROMIS)?fatigue vs. placebo and atomoxetine alone. However, there was variability in AHI reduction (i.e. 44% had an AHI reduction of more than 50%). Here, we sought to identify potential contributors to treatment response with AD109 75-2.5mg.

Methods: Response to treatment was defined as a ?50% reduction in AHI4 from baseline. In secondary analyses, patients were considered responders if the PROMIS?fatigue also improved. We considered that a low body mass index (BMI) would predict response to treatment (logistic regression). PROMIS?sleep impairment and ?fatigue scores were considered as secondary predictors. Analyses included adjustment for baseline AHI4, age and sex.

Results: Treatment response was associated with lower baseline BMI (OR [95%CI]: 2.94[1.18?10.00] per 1SD; N=34), higher baseline PROMIS?sleep impairment (3.00[1.12?10.38] per 1SD) and higher PROMIS?fatigue (2.82[0.96?12.30]). When PROMIS?fatigue was added to the response definition, associations were slightly attenuated (BMI: 2.50[1.06-7.69]; PROMIS?sleep impairment: 1.94[0.76?5.92; PROMIS?fatigue: (1.55[0.61?5.11]).

Conclusions: Responses to AD109 appear greatest in patients with reduced obesity and greater sleep apnea symptoms, who may therefore be most suitable for future trials.