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Bioavailability of a New Formulation of Nasal Naloxone for Prehospital Use

Primary Purpose

Drug Overdose

Status

Completed

Phase

Phase 1

Locations

Norway

Study Type

Interventional

Intervention

nasal naloxone

About this trial

This is an interventional treatment trial for Drug Overdose focused on measuring Emergency Treatment, Morphine Derivates, Heroin, Antidotes, Administration, Intranasal

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Department of Circulation and Medical Imaging

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

nasal naloxone

Arm Description

8 and 16 mg/ml, comparator 1 mg/ml. Three daily occasions with at least 3 days washout between treatment (min 8 days).

Outcomes

Primary Outcome Measures

bioavailability of naloxone

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 %

Secondary Outcome Measures

Maximum serum concentration (Cmax)

Time to maximum serum concentration (Tmax)

adverse events

will be reported from the start of the first session to the follow-up visit.

Full Information

NCT ID

NCT02158117

First Posted

June 2, 2014

Last Updated

February 2, 2017

Sponsor

Norwegian University of Science and Technology

Collaborators

St. Olavs Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02158117

Brief Title

Bioavailability of a New Formulation of Nasal Naloxone for Prehospital Use

Official Title

Bioavailability of a New Formulation of Nasal Naloxone for Prehospital Use

Study Type

Interventional

2. Study Status

Record Verification Date

February 2017

Overall Recruitment Status

Completed

Study Start Date

March 2014 (undefined)

Primary Completion Date

November 2014 (Actual)

Study Completion Date

November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Norwegian University of Science and Technology

Collaborators

St. Olavs Hospital

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Drug Overdose

Keywords

Emergency Treatment, Morphine Derivates, Heroin, Antidotes, Administration, Intranasal

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

nasal naloxone

Arm Type

Experimental

Arm Description

8 and 16 mg/ml, comparator 1 mg/ml. Three daily occasions with at least 3 days washout between treatment (min 8 days).

Intervention Type

Drug

Intervention Name(s)

nasal naloxone

Intervention Description

one puff in one nostril with the subject is lying down

Primary Outcome Measure Information:

Title

bioavailability of naloxone

Description

Time Frame

2 weeks

Secondary Outcome Measure Information:

Title

Maximum serum concentration (Cmax)

Time Frame

2 weeks

Title

Time to maximum serum concentration (Tmax)

Time Frame

2 weeks

Title

adverse events

Description

will be reported from the start of the first session to the follow-up visit.

Time Frame

2 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Toril A Nagelhus Hernes, phd prof

Organizational Affiliation

Norwegian University of Science and Technology

Official's Role

Study Director

Facility Information:

Facility Name

Department of Circulation and Medical Imaging

City

Trondheim

Country

Norway

12. IPD Sharing Statement

Citations:

PubMed Identifier

28144724

Citation

Tylleskar I, Skulberg AK, Nilsen T, Skarra S, Jansook P, Dale O. Pharmacokinetics of a new, nasal formulation of naloxone. Eur J Clin Pharmacol. 2017 May;73(5):555-562. doi: 10.1007/s00228-016-2191-1. Epub 2017 Jan 31.

Results Reference

result

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Bioavailability of a New Formulation of Nasal Naloxone for Prehospital Use

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