A Pilot Study of the Bioavailability of Nasal Naloxone

Study Overview
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Brief Summary
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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

Official Title
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A Pilot Study of the Bioavailability of Nasal Naloxone

Conditions
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Drug Overdose

Intervention / Treatment
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* Drug: naloxone intranasal
* Drug: naloxone intravenous


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: naloxone intranasal<br>2.0 mg by the nasal route | Drug: naloxone intranasal<br>* If bioavailability is 20% or 50 %, the dose will be equivalent to the clinical range 0.4 - 1.0 mg given parenterally<br>|
| Active Comparator: naloxone intravenous<br>1.0 mg intravenous | Drug: naloxone intravenous<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| preliminary bioavailability of nasal naloxone | 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. | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to maximum concentrations |  | 2 weeks | 
| maximum concentration |  | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antidotes, naloxone, administration, intravenous, administration, intranasal, pharmacology