Clinical Trial: Buccal Versus Injectable Naloxone: a Phase I Healthy Volunteer Study

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official 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 Subject

Brief 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 experim

Detailed Summary: Blood samples (3 ml) will be collected at -5, +1, 2, 3, 4, 6, 8, 10, 12.5, 15, 30, 45, 60, 75, 90, 120, 150, 180, 240, 300, 360, 420, and 480 minutes.
Sponsor: King's College London

Current Primary Outcome: Tmax [ Time Frame: Within 8-hour sampling period ]

Time elapsed till peak concentration


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Peak plasma concentration is assessed as Cmax [ Time Frame: Within 8-hour sampling period ]
    Peak concentration
  • Absorption of the active ingredient is determined as Area under the Curve (AUC) [ Time Frame: Within 8-hour sampling period ]
    Overall absorption (AUC = Area Under the Curve)
  • Absolute bioavailability of buccal naloxone relative to intravenous naloxone is assessed as F% [ Time Frame: Within 8-hour sampling period ]
    Absolute bioavailability relative to the IV reference (dose-corrected AUC for non-intravenous Buccal AUC divided by intravenous AUC multiplied by 100
  • Mean terminal half-life is assessed for all participants as T1/2 [ Time Frame: Within 8-hour sampling period ]
    mean terminal half-life


Original Secondary Outcome:

  • Cmax [ Time Frame: Within 8-hour sampling period ]
    Peak concentration
  • AUC [ Time Frame: Within 8-hour sampling period ]
    Overall absorption (AUC = Area Under the Curve)
  • F% [ Time Frame: Within 8-hour sampling period ]
    Absolute bioavailability relative to the IV reference (dose-corrected AUC for non-intravenous administration divided by intravenous AUC)
  • T1/2 [ Time Frame: Within 8-hour sampling period ]
    mean terminal half-life


Information By: King's College London

Dates:
Date Received: March 8, 2016
Date Started: June 2016
Date Completion: June 2017
Last Updated: May 16, 2016
Last Verified: May 2016