Buccal Versus Injectable Naloxone: a Phase I Healthy Volunteer Study
Status:
Unknown status
Trial end date:
2017-06-01
Target enrollment:
Participant gender:
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).
The investigators 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).
The investigators propose a pharmacokinetic pilot investigation with within-subjects
(crossover) 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. The investigators 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.