Drug Overdose
Conditions
Keywords
Emergency Treatment, Morphine Derivates, Heroin, Antidotes, Administration, Intravenous, Pharmacology, Naloxone, Healthy volunteers, Administration, intramuscular, Administration, intranasal
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.
Interventions
DRUGIntranasal (IN) naloxone 1x
Administered as 100 μl 14.0 mg/ml (1.4 mg naloxone) by Aptar Unitdose device as one puff in one nostril
DRUGIntranasal (IN) naloxone 2
Administered as 2x 100 μl 14 mg/ml (2.8 mg naloxone) by Aptar Unitdose device as two puffs within the same nostril with 3 minutes interval
Administered as 1 ml Naloxon B Braun 0.4 mg/ml (0.4 mg naloxone), in an intravenous cannula in the opposite arm of which the blood samples are drawn from. IV bolus will be given rapidly (in less than 5 seconds)
Naloxone administered as 2 ml Naloxon B Braun 0.4 mg/ml (0.8 mg naloxone) in a Braun Omnifix 2.5 ml syringe using a BD Microlance 3 21G (green) 0.8x40 mm needle in the deltoid muscle of the non-dominant arm
Sponsors
St. Olavs Hospital
A/S Den norske Eterfabrikk
Smerud Medical Research International AS
Norwegian University of Science and Technology
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Peak plasma concentration (Cmax) | 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) | 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) | 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) | 4 days | Tmax will be compared for single dose IN, IM and IV naloxone |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute bioavailability | 4 days | assessed by comparing dose adjusted systemic exposure (AUC0-last) of IN and IV naloxone |
| Relative bioavailability | 4 days | assessed by comparing dose adjusted systemic exposure (AUC0-last) of IN and IM naloxone |
| Dose proportionality | 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. |
Countries
Norway
Outcome results
None listed