Apnimed, a clinical-stage pharmaceutical company focused on developing oral pharmacologic treatments to address obstructive sleep apnea (OSA) and related disorders, reports positive topline results from a proof-of-concept randomized, controlled, double-blind, single-dose, three-period crossover study (protocol APX-001) in patients with OSA evaluating sleep apnea pill candidates AD504 and AD182.

Patients treated with sleep apnea pill candidate AD504 (atomoxetine plus trazodone) showed a strong trend in the reduction in apnea hypopnea index (AHI) from placebo, which was the study’s primary endpoint. Additionally, the study’s secondary endpoint was met with a significant reduction of sleep apnea specific hypoxic burden (HB), which evidence suggests is a predictor of adverse cardiovascular outcomes in people with OSA, following treatment with AD504. A second drug, AD182 (atomoxetine and an orexin antagonist) was also studied and demonstrated a positive trend in the reduction of HB.

“We’re pleased with the reduction in HB demonstrated by AD504 in this small, proof-of-concept, Phase 2 study,” says Larry Miller, MD, CEO of Apnimed, in a release. “In our pursuit to deliver breakthrough oral medications to patients with OSA, we are exploring multiple drug combinations and patient subpopulations. This drug combination involving a medication commonly prescribed for sleep problems could particularly benefit OSA patients with disturbed sleep—difficulty initiating and maintaining sleep—which we believe represents an important sub-population of OSA patients.”

Study APX-001 Data Summary: A Phase 2 Clinical Trial Exploring AD504 and AD182 in OSA Patients (NCT04645524)

This was a proof-of-concept, randomized, controlled, double-blind, single-dose, three-period crossover study of 15 patients who met eligibility criteria. Each patient received one night of AD504 (atomoxetine and trazodone), one night of AD182 (atomoxetine and an orexin antagonist), and one night of placebo. Doses were given immediately prior to bedtime.

AD504 showed a strong trend in reduction of AHI from placebo (from 18.2[11.8-31.3] events/hour to 7.4[5.4-16.1] events/hour, p=0.06) and a significant reduction in HB from placebo (from 48.2[31.2-79.6] to 18.7[14.9-43.5] %min/hour, p<0.001). AD182 also demonstrated a trend towards reduction in HB relative to placebo. Both combination drugs also demonstrated a favorable safety profile.

AD504 is an investigational, oral pharmacologic combination dosed once daily at bedtime, AD504 may be beneficial for OSA patients who also experience sleep disturbance. AD504 is Apnimed’s second core program and is a combination of atomoxetine and trazodone.

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