Clin Transl Sci. 2026 Jul;19(7):e70640. doi: 10.1111/cts.70640.
ABSTRACT
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/m2. Naloxone concentrations increased similarly over 15 min and doubled for the AP003 group at 20 min, thereby meeting the primary objective. There was a dose-dependent increase in Cmax, AUC0-inf, pAUC, and AUC0-t; however, statistical significance for dose proportionality was not seen in AUC0-inf, AUC0-t, and Cmax. All treatment emergent adverse events were mild or moderate in severity and no serious adverse events were reported.
PMID:42332351 | DOI:10.1111/cts.70640
