Buccal versus Injectable Naloxone: a Phase I Healthy Volunteer Study
Research type
Research Study
Full title
A Pilot, Phase 1, Open-Labelled, 4 Period, Randomised, Crossover Study to Evaluate the Pharmacokinetics of Naloxone when Given by the IV, IM and Buccal Routes of Administration in Healthy Male Subjects
IRAS ID
125173
Contact name
John Strang
Contact email
Sponsor organisation
Clinical Trials Office, King's College London
Eudract number
2014-001802-16
Duration of Study in the UK
0 years, 6 months, 1 days
Research summary
Naloxone is the standard treatment in response to cases of suspected opiate overdose.
Buccal formulation of naloxone is a novel alternative to the licensed naloxone injection which, by removing the risk of accidental needle-stick, may be safer and easier to administer.
Current UK policy allows the emergency administration of naloxone by any member of the general public (Strang, Kelleher, Best, Mayet, & Manning, 2006), and the preventative provision of naloxone to drug users and their family members (“take-home naloxone”) is possible on a prescription basis.
Thus, buccal naloxone may be particularly suitable for administration by family members who are providing interim overdose management care while awaiting the arrival of an ambulance.
The aim of this study is to examine the bioavailability and dose proportionality of buccal naloxone compared with the licensed injection standards (intravenous, intramuscular).
We hypothesise that buccal naloxone is not inferior to the injection reference in absorption kinetics, i.e. time elapsed till peak concentration (Tmax; primary outcome), peak plasma concentration (Cmax), overall absorption (AUC), bioavailability (F%) and, duration of action (mean terminal half-life; T1/2).
We propose a pharmacokinetic pilot investigation with within-subjects (cross-over) design, comparing two doses (0.8 mg; 1.6 mg) of buccal naloxone-hydrochloride solution to the licensed intramuscular (IM; 0.8 mg) and intravenous (IV; 0.8 mg) routes of injection.. We will invite four healthy (i.e., non-opioid using) male volunteers (n=4, not powered), each of whom will attend four experimental sessions at counterbalanced sequence. Each volunteer will receive naloxone-hydrochloride doses of 0.8 mg IM, 0.8 mg IV, 0.8 mg buccal, and 1.6 mg buccal, with only one dose administered per session.
Blood concentrations will be measured at selected times during each session to establish speed of naloxone absorption, time to peak concentration, estimated half-life, and overall bioavailability.
This dose-ranging pilot will inform future work by providing preliminary data on buccal naloxone absorption into the bloodstream and by establishing feasibility of the buccal route for naloxone delivery.REC name
London - London Bridge Research Ethics Committee
REC reference
15/LO/0103
Date of REC Opinion
23 Mar 2015
REC opinion
Further Information Favourable Opinion