Obstructive sleep apnea (OSA) is common and has major health implications but treatment options are limited. In previous research atomoxetine and oxybutynin showed promising effect at reducing OSA severity, however they reduced arousal threshold, one of the key traits responsible for OSA. Since oxybutynin was used mainly as a hypnotic, but it is burdened by several anti-cholinergic side effects, DAW2020, a hypnotic which prolonged the total sleep time in a previous trial in OSA patients, could be a better candidate to associate with atomoxetine.

Two overnight sleep studies will be performed: a drug night and a placebo night, with a month of washout between treatments. The patient will breath spontaneously (without CPAP) for both nights. On the study nights, subjects will present to the laboratory in the evening and be instrumented with a full polysomnography for monitoring sleep, physiological variables (endotypes), and respiratory events. A history and physical examination will be performed on each night prior to beginning the study, as will a urine pregnancy test in premenopausal women. The drugs will be administered as follows. There will be a 3-day run in of atomoxetine 40 mg followed by atomoxetine 80 mg starting on the fourth night until the night of the study. DAW2020 34 mg will be administered for 1-week to allow adequate plasma concentrations to be reached. For the sleep study, at least four hours of sleep (50% in the supine position) will be monitored to assess sleep and respiratory variables.

Inclusion Criteria:

• Moderate-to-severe OSA (AHI ≥ 15 events/hr)

Exclusion Criteria:

• All participants will be healthy and without major organ system disease that would preclude undergoing the physiological measurements.
• Use of medications expected to stimulate or depress respiration (including opioids, barbiturates, acetazolamide, doxapram, almitrine, theophylline, 4-hydroxybutanoic acid).
• Use of SNRIs/SSRIs.
• Conditions likely to affect OSA physiology: neuromuscular disease or other major neurological disorder, heart failure (also below), or any other unstable major medical condition.
• Sleep disordered breathing or respiratory disorders other than obstructive sleep apnea:
• Other sleep disorders: periodic limb movements (periodic limb movement arousal index > 10/hr), narcolepsy, or parasomnias.
• Hypersensitivity to the study drug (angioedema or urticaria)
• Contraindications to DAW2020
• Use of medications that lengthen QTc interval
• Hypokaliemia, hypomagnesemia, uncontrolled thyroid disease
• Severe claustrophobia.