A Phase 1, Open-Label, Randomized Study to Investigate the Pharmacokinetics and Safety of Multiple Doses of Intranasal Naloxone in Healthy Participants.

This was a Phase 1, open label, randomized, crossover study to evaluate the safety and pharmacokinetics of multiple doses of intranasal naloxone (NCT05377255). Twenty-four healthy participants were enrolled at a single site in the US to one of two sequences. Participants received four doses of 4 mg intranasal (IN) naloxone using two two-dose devices (AP003; single dose at 0, 2.5, 5.0, and 7.5 min) or two doses of 4 mg naloxone using two one-dose devices (single dose at 0 and 2.5 min). Treatments were separated by a 48-h washout, the order being driven by the crossover sequence. Blood samples were collected predose and at defined timepoints post-dosing for analysis of free and total naloxone, which were used for the noncompartmental PK analysis. Safety was assessed through physical exams, vital signs, electrocardiograms, continuous cardiac monitoring, clinical labs, olfactory assessments, rhinoscopy, and treatment emergent adverse events. Of the 24 participants, most were Female (n = 14, 58.3%), White (n = 20, 83.3%), and Hispanic or Latino (n = 24, 100%), with a mean age of 38.1 years and baseline body mass index of 26.2 kg/m