Buccal and sublingual lyophilised naloxone for opioid overdose reversal: A Phase 1 open-label, random-sequence crossover pharmacokinetic study protocol in healthy volunteers (NalBuc).

Authors

Mariana Gonzalez Utrilla, Alexander Baker, Edward Chesney, Kim Lee, Richard Emsley, John Strang

Published in

PloS one. Volume 21. Issue 10. Pages e0347370. Epub Oct 27, 2026.

Abstract

Opioid overdose remains a major global public health emergency, with naloxone being an essential response. Benefit from existing naloxone formulations is limited by barriers to acceptability, fixed dosing, and poor real-world carriage. This study describes the protocol for a Phase 1 exploratory investigation of a novel ultra-portable lyophilised naloxone wafer designed to facilitate constant carriage and enable rapid mucosal absorption.
This open-label, randomised, random-sequence, five-way crossover pharmacokinetic (PK) exploratory study will recruit 12-15 healthy adults at a UK clinical research facility. Participants will receive five treatments, each separated by ≥36 hours: buccal naloxone wafer 2 mg, buccal wafer 4 mg, sublingual wafer 2 mg, intramuscular naloxone 0.4 mg, and intranasal naloxone 1.8 mg (Nyxoid®). Blood samples will be collected up to 240 minutes post-dose for PK analysis via validated LC-MS/MS methods. The primary endpoint is time to maximum plasma concentration (Tmax). Secondary endpoints include Maximum Plasma Concentration (Cmax), Time to 50% of maximum concentration (T50%), Area Under the Curve from time zero to 15 minutes (AUC0-15), Area Under the Curve from time zero to infinity (AUCinf), and safety/tolerability. Dose-proportionality and buccal-sublingual comparisons will be explored. Trial Registration:REC: 25/LO/0701; MHRA CTA (IRAS): 1011060. ISRCTN67173532.
This study will characterise the absorption profile, early exposure, and relative bioavailability of a novel naloxone wafer formulated for rapid buccal and sublingual administration. Findings will inform whether this technology could provide a practical, effective alternative to current injectable and intranasal products, with potential to substantially improve naloxone carriage and timely overdose response, and will guide the design of a subsequent, larger confirmatory study.

PMID:
42945264
Bibliographic data and abstract were imported from PubMed on 28 Oct 2026.

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