Bioavailability of Nasal Naloxone and Injected Naloxone Compared

Drug Overdose Clinical Trial

— OPI-15-002  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02598856
• Other study ID #: OPI 15-002
• Secondary ID: 2015-002355-10
• Status: Completed
• Phase: Phase 1
• First received: November 2, 2015
• Last updated: February 2, 2017
• Start date: March 2016
• Est. completion date: December 2016

Study information

• Verified date: February 2017
• Source: Norwegian University of Science and Technology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Drug Overdose

Intervention

Drug:
• Intranasal (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
• Intranasal (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
• Intravenous (IV) naloxone
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)
• Intramuscular (IM) naloxone
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

Locations

Country	Name	City	State
Norway	Department of Circulation and Medical Imaging	Trondheim

Sponsors (4)

Lead Sponsor	Collaborator
Norwegian University of Science and Technology	A/S Den norske Eterfabrikk, Smerud Medical Research International AS, St. Olavs Hospital

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in Peak plasma concentration (Cmax)	Cmax will be compared for single dose IN, IM and IV naloxone	4 days
Primary	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
Primary	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
Primary	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	Dose proportionality	assessed by comparing systemic exposure (AUC0-last) following one and two doses of 1.4 mg of IN naloxone in the same nostril.	4 days
Secondary	Absolute bioavailability	assessed by comparing dose adjusted systemic exposure (AUC0-last) of IN and IV naloxone	4 days
Secondary	Relative bioavailability	assessed by comparing dose adjusted systemic exposure (AUC0-last) of IN and IM naloxone	4 days