Bioavailability of Nasal Naloxone and Injected Naloxone Compared
OPI-15-002
2 other identifiers
interventional
22
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Mar 2016
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 2, 2015
CompletedFirst Posted
Study publicly available on registry
November 6, 2015
CompletedStudy Start
First participant enrolled
March 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2016
CompletedFebruary 3, 2017
February 1, 2017
9 months
November 2, 2015
February 2, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Difference in Peak plasma concentration (Cmax)
Cmax will be compared for single dose IN, IM and IV naloxone
4 days
Difference in systemic exposure: Area under the plasma concentration versus time curve (AUC-0last)
AUC 0-last will be compared for single dose IN, IM and IV naloxone
4 days
Difference in dose adjusted systemic exposure: Area under the plasma concentration versus time curve (AUC-0inf)
AUC0-inf will be compared for single dose IN, IM and IV naloxone
4 days
Difference in time at which the Cmax is observed (Tmax)
Tmax will be compared for single dose IN, IM and IV naloxone
4 days
Secondary Outcomes (3)
Dose proportionality
4 days
Absolute bioavailability
4 days
Relative bioavailability
4 days
Study Arms (4)
Intranasal naloxone 1x
EXPERIMENTALEach subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
Intranasal naloxone 2x
ACTIVE COMPARATOREach subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
Intravenous naloxone
ACTIVE COMPARATOREach subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
Intramuscular naloxone
ACTIVE COMPARATOREach subject will receive one dose of IN naloxone 1.4 mg, IN naloxone 2 x 1.4 mg, IV naloxone 0.4 mg and IM naloxone 0.8 mg in a randomized order. The four doses will be given at four different visits with a washout period of at least 72 hours between. One follow-up visit will be conducted within one month after the last exposure.
Interventions
Administered as 100 μl 14.0 mg/ml (1.4 mg naloxone) by Aptar Unitdose device as one puff in one nostril
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
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Norwegian University of Science and Technologylead
- St. Olavs Hospitalcollaborator
- A/S Den norske Eterfabrikkcollaborator
- Smerud Medical Research International AScollaborator
Study Sites (1)
Department of Circulation and Medical Imaging
Trondheim, Norway
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Toril A Nagelhus Hernes, phd prof
Norwegian University of Science and Technology
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 2, 2015
First Posted
November 6, 2015
Study Start
March 1, 2016
Primary Completion
December 1, 2016
Study Completion
December 1, 2016
Last Updated
February 3, 2017
Record last verified: 2017-02