Bioavailability of a New Formulation of Nasal Naloxone for Prehospital Use

Drug Overdose Clinical Trial

Official title:

Bioavailability of a New Formulation of Nasal Naloxone for Prehospital Use

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02158117
• Other study ID #: OPI-13-001
• Status: Completed
• Phase: Phase 1
• First received: June 2, 2014
• Last updated: February 2, 2017
• Start date: March 2014
• Est. completion date: November 2014

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Drug Overdose

Intervention

Drug:
• nasal naloxone
one puff in one nostril with the subject is lying down

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Norwegian University of Science and Technology	St. Olavs Hospital

Country where clinical trial is conducted

Norway, 

References & Publications (1)

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 Jan 31. doi: 10.1007/s00228-016-2191-1. [Epub ahead of print] — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 %	2 weeks
Secondary	Maximum serum concentration (Cmax)		2 weeks
Secondary	Time to maximum serum concentration (Tmax)		2 weeks
Secondary	adverse events	will be reported from the start of the first session to the follow-up visit.	2 weeks