Bioavailability of a New Formulation of Nasal Naloxone for Prehospital Use

Overdose with potential deadly outcome is a serious problem among opioid abusers, not least in Norway. The annual death toll from overdose is about 250, twice the annual death toll from traffic accidents. Those who inject heroin or other opioids are considered to have the highest risk for death from overdose. To save lives, immediate treatment with a μ-opioid antidote such as naloxone is required. Usually naloxone is injected into a muscle or a blood vessel. Administration of naloxone via the nose has been suggested as an alternative for use by emergency teams and possibly also bystanders. This is not only an easier way to give naloxone, but would also eliminate the risk for needle stick injuries and blood contamination. A pilot study in this hospital has shown no significant side effects or adverse reaction. While significant benefits are expected from developing an adequately formulated naloxone nasal spray for pre-hospital use, the risks to participants are minimal. Therefore this preclinical study in healthy volunteers will be undertaken.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Trondheim, Norway
        • Department of Circulation and Medical Imaging

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy
  • Normal electrocardiogram (ECG)
  • Hemoglobin: male 13.4 - 17.0 g/dL, female 11,7- 15.3 g/dL
  • Creatinine: male 60- 105 micromol/L female 45- 90 micromol/L
  • ASAT: male 15- 45 U/L, female 15- 35 U/L
  • ALAT: male 10- 70 U/L female 10- 45 U/L
  • Gamma GT: male 10- 80 U/L female 10- 45 U/L
  • HCG normal under 3 ye/L
  • Fertile women must use safe contraception and have a negative serum HCG at inclusion

Exclusion Criteria:

  • Taking any medications including herbal medicines the last week prior to first treatment visit
  • History of drug abuse
  • History of prior drug allergy
  • Having any local nasal disease or nasal surgery or recent cold for the last week
  • Pregnancy
  • Fertile women not using high efficacy contraceptives (Oral contraceptives, Patch (Evra), Implants, Vaginal ring, Hormonal IUD, Copper IUD, Sterilization) throughout the study period until their last visit.
  • Lactating women
  • Any reason why, in the opinion of the investigator, the patient should not participate

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: nasal naloxone
8 and 16 mg/ml, comparator 1 mg/ml. Three daily occasions with at least 3 days washout between treatment (min 8 days).
one puff in one nostril with the subject is lying down

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
bioavailability of naloxone
Time Frame: 2 weeks
A LCMSMS method for determination of Naloxone in serum was developed using acetonitrile protein precipitation. Naloxone D5 was used as internal standard and quantitative determination was done by using Sciex Analyst version 1.5. The method is fully validated by assessing linearity, accuracy, precision, sensitivity, specificity/selectivity, in process and storage stability, dilution integrity and assay ruggedness according to Dadgar (1995) and Shah (1991). The method was found linear, accurate and precise across the dynamic range of 0.05 to 45 ng/ml. Limit of quantification (LOQ) was 0.05ng/ml with CV = 12.7% and inaccuracy < 7.8% (n = 17). Quality Controls (QC) in middle (n=18) and upper (n=18) calibration range had CV < 4.2% and inaccuracy <8.2 %
2 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum serum concentration (Cmax)
Time Frame: 2 weeks
2 weeks
Time to maximum serum concentration (Tmax)
Time Frame: 2 weeks
2 weeks
adverse events
Time Frame: 2 weeks
will be reported from the start of the first session to the follow-up visit.
2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2014

Primary Completion (Actual)

November 1, 2014

Study Completion (Actual)

November 1, 2014

Study Registration Dates

First Submitted

June 2, 2014

First Submitted That Met QC Criteria

June 4, 2014

First Posted (Estimate)

June 6, 2014

Study Record Updates

Last Update Posted (Estimate)

February 3, 2017

Last Update Submitted That Met QC Criteria

February 2, 2017

Last Verified

February 1, 2017

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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