Clinical trial NCT02598856: Bioavailability of Nasal Naloxone and Injected Naloxone Compared
Official title: Bioavailability of Nasal Naloxone and Injected Naloxone Compared. A Randomized, Open Label, 4-way Cross-over Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Drug Overdose
Keywords: Emergency Treatment
Morphine Derivates
Heroin
Antidotes
Administration, Intravenous
Pharmacology
Naloxone
Healthy volunteers
Administration, intramuscular
Administration, intranasal
Lead sponsor: Norwegian University of Science and Technology
Sponsor class: OTHER
Collaborators: name: St. Olavs Hospital
name: A/S Den norske Eterfabrikk
name: Smerud Medical Research International AS
First posted: 2015-11-06
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

In order to participate in this study the subjects must meet all of the following inclusion criteria:

* Provision of a signed written informed consent
* ECG without any pathological abnormalities
* Have a BMI range of 18.5- 26.0 kg/m
* Female subject with child bearing potential must use high efficacy contraception. For the purpose of this study acceptable contraception is defined as sterilization, oral contraceptives, patch, implants, vaginal ring, hormonal IUD or copper IUD through out the study until the last visit.
* Laboratory values within reference values for the following haematology and biochemistry tests:

  * Haemoglobin
  * Creatinine
  * ASAT
  * ALAT
  * Gamma GT

Exclusion Criteria:

In order to participate in the study subjects must not meet any of the following exclusion criteria:

* using medication on a regular basis, including regular use of nasal spray of any form.
* History of prior drug allergy
* local nasal disease or nasal surgery for the last 2 months
* Pregnant or breast feeding women. A serum HCG below 3 U/L must be demonstrated in females of child-bearing potential at Screening Visit.
* Current drug or alcohol abuse, which in the opinion of the Investigator should preclude participation in the study.
* Having received another new medical chemical entity (defined as a compound which has not been approved for marketing) or having participated in any other clinical study that included drug treatment within 3 months of the administration of investigational product in this study.
* Hypersensitivity to naloxone or any of its excipients.
* Investigator considers subject unlikely to comply with study procedures, restrictions and/or other requirements.

Primary outcomes:
measure: Difference in Peak plasma concentration (Cmax)
timeFrame: 4 days
measure: Difference in systemic exposure: Area under the plasma concentration versus time curve (AUC-0last)
timeFrame: 4 days
measure: Difference in dose adjusted systemic exposure: Area under the plasma concentration versus time curve (AUC-0inf)
timeFrame: 4 days
measure: Difference in time at which the Cmax is observed (Tmax)
timeFrame: 4 days
Secondary outcomes:
measure: Dose proportionality
timeFrame: 4 days
measure: Absolute bioavailability
timeFrame: 4 days
measure: Relative bioavailability
timeFrame: 4 days
Other outcomes:
Locations:
city: Trondheim
country: Norway
facility: Department of Circulation and Medical Imaging
Study officials:
affiliation: Norwegian University of Science and Technology
name: Toril A Nagelhus Hernes, phd prof
role: STUDY_DIRECTOR
References: