Clinical Trial: Bioavailability of Nasal Naloxone and Injected Naloxone Compared

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Bioavailability of Nasal Naloxone and Injected Naloxone Compared. A Randomized, Open Label, 4-way Cross-over Study

Brief Summary:

Opioid overdoses have in the last decade counted for about 230 untimely deaths annually in Norway. The government is currently implementing a strategy for combating this epidemic. Among the actions promoted in this strategy is the distribution of naloxone for intranasal administration. Such administration of naloxone is currently being implemented and tried out around the world, but very little has been done to pharmacologically study this new route of administration of this well known drug, and only 3 open label randomized controlled trials (RCTs) have been conducted. A recent guideline from the WHO on community management of opioid overdoses is a comprehensive review of many of the aspects the investigators cover in our research.

Regarding both dosage, routes of administration of naloxone and care of these patients in the pre hospital setting. The WHO calls for nasal formulations with a higher concentration, as well as focuses on the current wide spread off label use of nasal naloxone as a problem and identifies several research questions of critical importance and very low evidence.The current study, together with our research group's previous and future studies, aims to provide data for the development of a medicinal product with marketing authorisation for use in pre-hospital overdoses. This to contribute to public health measures for opioid users and those around them.


Detailed Summary:
Sponsor: Norwegian University of Science and Technology

Current Primary Outcome:

  • Difference in Peak plasma concentration (Cmax) [ Time Frame: 4 days ]
    Cmax will be compared for single dose IN, IM and IV naloxone
  • Difference in systemic exposure: Area under the plasma concentration versus time curve (AUC-0last) [ Time Frame: 4 days ]
    AUC 0-last will be compared for single dose IN, IM and IV naloxone
  • Difference in dose adjusted systemic exposure: Area under the plasma concentration versus time curve (AUC-0inf) [ Time Frame: 4 days ]
    AUC0-inf will be compared for single dose IN, IM and IV naloxone
  • Difference in time at which the Cmax is observed (Tmax) [ Time Frame: 4 days ]
    Tmax will be compared for single dose IN, IM and IV naloxone


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Dose proportionality [ Time Frame: 4 days ]
    assessed by comparing systemic exposure (AUC0-last) following one and two doses of 1.4 mg of IN naloxone in the same nostril.
  • Absolute bioavailability [ Time Frame: 4 days ]
    assessed by comparing dose adjusted systemic exposure (AUC0-last) of IN and IV naloxone
  • Relative bioavailability [ Time Frame: 4 days ]
    assessed by comparing dose adjusted systemic exposure (AUC0-last) of IN and IM naloxone


Original Secondary Outcome: Same as current

Information By: Norwegian University of Science and Technology

Dates:
Date Received: November 2, 2015
Date Started: March 2016
Date Completion:
Last Updated: February 2, 2017
Last Verified: February 2017