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Completed

NCT Number: NCT02598856

Bioavailability of Nasal Naloxone and Injected Naloxone Compared

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.

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Key information

Conditions

Drug Overdose Chemically-Induced Disorders Drug Misuse Mental Disorders Prescription Drug Misuse Substance-Related Disorders

Age range

18 year–40 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Department of Circulation and Medical Imaging

Trondheim, Norway

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Intranasal (IN) naloxone 1x

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

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

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

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

Primary outcomes

  1. Difference in Peak plasma concentration (Cmax)

    Time frame: 4 days

    Cmax will be compared for single dose IN, IM and IV naloxone

  2. Difference in systemic exposure: Area under the plasma concentration versus time curve (AUC-0last)

    Time frame: 4 days

    AUC 0-last will be compared for single dose IN, IM and IV naloxone

  3. Difference in dose adjusted systemic exposure: Area under the plasma concentration versus time curve (AUC-0inf)

    Time frame: 4 days

    AUC0-inf will be compared for single dose IN, IM and IV naloxone

  4. Difference in time at which the Cmax is observed (Tmax)

    Time frame: 4 days

    Tmax will be compared for single dose IN, IM and IV naloxone

Secondary outcomes

  1. Dose proportionality

    Time frame: 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.

  2. Absolute bioavailability

    Time frame: 4 days

    assessed by comparing dose adjusted systemic exposure (AUC0-last) of IN and IV naloxone

  3. Relative bioavailability

    Time frame: 4 days

    assessed by comparing dose adjusted systemic exposure (AUC0-last) of IN and IM naloxone

Sponsors and collaborators

Lead sponsor

Norwegian University of Science and Technology

Other

Collaborators

  • A/S Den norske Eterfabrikk
  • Smerud Medical Research International AS
  • St. Olavs Hospital

Registry information

Official study title

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

Acronym: OPI-15-002

Important dates

Study start
2016
Primary completion
2016
Study completion
2016
First posted
Nov 6, 2015
Registry last updated
Feb 3, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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