A Pilot Study of the Bioavailability of Nasal Naloxone

Sponsor

Norwegian University of Science and Technology (Other)

Overall Status

Completed

CT.gov ID

NCT01939444

Collaborator

St. Olavs Hospital (Other), University of Iceland (Other)

Enrollment

Location

Arms

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The overall is aim of this pilot study is to give a preliminary estimation of key parameters of the pharmacokinetics of a proper formulation of intranasal naloxone. These data will be used to design a well justified protocol for the final estimation of these parameters:

Preliminary estimation of bioavailability of this intranasal naloxone in human, healthy volunteers
Preliminary estimation of the maximum serum concentration (Cmax) of this formulation
Preliminary estimation of the time to maximum serum concentration (Tmax) of this formulation
Safety of the formulation

Condition or Disease	Intervention/Treatment	Phase
Drug Overdose	Drug: naloxone intranasal Drug: naloxone intravenous	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

A Pilot Study of the Bioavailability of Nasal Naloxone

Study Start Date :

Aug 1, 2013

Actual Primary Completion Date :

Oct 1, 2014

Actual Study Completion Date :

Nov 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: naloxone intranasal 2.0 mg by the nasal route	Drug: naloxone intranasal If bioavailability is 20% or 50 %, the dose will be equivalent to the clinical range 0.4 - 1.0 mg given parenterally
Active Comparator: naloxone intravenous 1.0 mg intravenous	Drug: naloxone intravenous The parenteral dose reflects clinically used doses for overdoses (0.4 - 1.0 mg). A washout period of at least 3 days between each intervention. IV naloxone (Naloxone B. Braun 0.4mg/ml) administered slowly over 1-2 min in the recumbent position

Arm

Intervention/Treatment

Experimental: naloxone intranasal

2.0 mg by the nasal route

Drug: naloxone intranasal

If bioavailability is 20% or 50 %, the dose will be equivalent to the clinical range 0.4 - 1.0 mg given parenterally

Active Comparator: naloxone intravenous

1.0 mg intravenous

Drug: naloxone intravenous

The parenteral dose reflects clinically used doses for overdoses (0.4 - 1.0 mg). A washout period of at least 3 days between each intervention. IV naloxone (Naloxone B. Braun 0.4mg/ml) administered slowly over 1-2 min in the recumbent position

Outcome Measures

Primary Outcome Measures

preliminary bioavailability of nasal naloxone [2 weeks]
measured as ratio of area under the time concentration curve for nasal over intravenous naloxone x 100. Plasma concentration data will be analyzed by non-compartmental techniques.

Secondary Outcome Measures

time to maximum concentrations [2 weeks]
maximum concentration [2 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

healthy (adequate organ function is determined by electrocardiogram (ECG), liver and kidney clinical chemistry, and a standard clinical examination/interview. For safety reasons we may ask for urine sample for analysis of opioids)
informed consent

Exclusion Criteria:

history of liver disease
taking any medications including herbal medicines the last week history of drug abuse
any local nasal disease or nasal surgery or recent cold for the last week
any history of drug allergies