Bioavailability of Nasal Naloxone and Injected Naloxone Compared

NCT ID: NCT02598856

Last Updated: 2017-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2016-12-31

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.

Conditions

Drug Overdose

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Intranasal naloxone 1x

Each 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.

Group Type: EXPERIMENTAL

Intranasal (IN) naloxone 1x

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intranasal naloxone 2x

Each 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.

Group Type: ACTIVE_COMPARATOR

Intranasal (IN) naloxone 1x

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intravenous naloxone

Each 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.

Group Type: ACTIVE_COMPARATOR

Intranasal (IN) naloxone 1x

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intramuscular naloxone

Each 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.

Group Type: ACTIVE_COMPARATOR

Intranasal (IN) naloxone 1x

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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)

Intervention Type: DRUG

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

Intervention Type: DRUG

Eligibility Criteria

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

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

St. Olavs Hospital

OTHER

Sponsor Role: collaborator

A/S Den norske Eterfabrikk

INDUSTRY

Sponsor Role: collaborator

Smerud Medical Research International AS

OTHER

Sponsor Role: collaborator

Norwegian University of Science and Technology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Toril A Nagelhus Hernes, phd prof

Role: STUDY_DIRECTOR

Norwegian University of Science and Technology

Locations

Department of Circulation and Medical Imaging

Trondheim, , Norway

Countries

Norway

Other Identifiers

2015-002355-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

OPI 15-002

Identifier Type: -

Identifier Source: org_study_id