Investigational Sleep Apnea Drug to Move to Phase 2 Trial0

Apnimed, a clinical-stage pharmaceutical company focused on developing medicines to treat sleep apnea and related disorders, reports the results of a Phase 1 study for a component of the company’s lead combination drug candidate, AD109, which is being explored as a pharmacologic treatment for obstructive sleep apnea (OSA). In this healthy volunteer study, R-oxybutynin, a key component of AD109, demonstrated a favorable pharmacokinetic (PK) profile and was well tolerated with no adverse events related to the study drug.

“Obstructive sleep apnea represents a significant public health problem in the US and around the globe and current treatment options do not meet the needs of patients,” says Larry Miller, MD, Apnimed CEO, in a release. “We believe that AD109, an oral drug candidate dosed once-daily at bedtime, could be a significant breakthrough for these patients by giving them a simple, safe, and effective solution that does not require a CPAP device or surgery. The results from this study support our advancement of this program.

“We look forward to initiating a Phase 2 study with AD109 in Q4 of this year.”

[RELATED: Treating Sleep Apnea with Pills Instead of Machines]

AD109 consists of the norepinephrine reuptake inhibitor (NRI) atomoxetine combined with the antimuscarinic R-oxybutynin. The study, called APC-001, was a Phase 1, randomized, single-dose, open-label, two-way crossover study conducted to evaluate the safety, tolerability, and PK of 2.5 mg of R-oxybutynin compared to 5 mg of racemic (R,S) oxybutynin in 24 healthy adult volunteers. While S-oxybutynin has been studied as a bladder antispasmodic, most of the antimuscarinic activity of racemic oxybutynin necessary to activate the upper airway muscles and maintain an open airway during sleep is thought to be mediated by R-oxybutynin. By purifying the R-oxybutynin and removing the S-oxybutynin, unwanted bladder effects can potentially be reduced and a lower dose of R-oxybutynin alone, relative to racemic oxybutynin, may be effective to treat OSA.

Study participants received treatments in random order, administered as a single oral dose, with a washout period between treatments of at least 7 days. The results indicated that R-oxybutynin was well-tolerated and that there were no adverse events related to the study drug. The blood plasma concentrations of the 2.5 mg dose of R-oxybutynin, when administered alone, closely matched the profile of R-oxybutynin when dosed as 5 mg of racemic oxybutynin.

Additionally, no interconversion to S-oxybutynin was observed following administration of 2.5 mg R-oxybutynin.

Apnimed’s lead product candidate, AD109, targets neurotransmitter levels in the central nervous system to activate upper airway muscles and maintain an open airway during sleep. AD109 is a first-in-class, oral pharmaceutical combination dosed once-daily at bedtime, designed to treat OSA patients across a broad spectrum of disease severity.

Proof of concept for the AD109 program was demonstrated in Apnimed study APN-002, a Phase 2, parallel group dose-finding study of the combination of atomoxetine and racemic oxybutynin. That study provided evidence of safety and efficacy of a norepinephrine reuptake inhibitor (NRI) + antimuscarinic combination in 140 patients.

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