Pharmacokinetic Evaluation of Intranasal Nalmefene Using Three Dosing Regimens

Study Overview
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Brief Summary
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This study is to compare the pharmacokinetics (how the body absorbs, breaks down and eliminates drug from your body) of nalmefene when given as a single dose intranasally (IN;into the nose), as a single dose in each nostril and as two doses in one nostrils; and to evaluate the safety and tolerability of nalmefene IN.

Detailed Description
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Open-label, randomized, 3-period, 3-treatment, 6-sequence, ranodmised crossover study in 24 healthy volunteers. Subjects will be assigned to each of the 6 possible sequences. Each subject will receive 3 intranasal (IN) nalmefene doses: 3mg IN dose (one 0.1mL spray of a 30mg/mL solution in one nostril) 6mg IN dose (one 0.1mL spray of a 30mg/mL solution in each nostril) 6mg IN dose (two 0.1mL sprays of a 30mg/mL solution in one nostril) There will be a 6 day washout period between doses. Screening can occur up to 28 days before admission, subjects will then stay in the inpatient facility for 16 days to complete the treatment phase of the study and will be discharged following completion of the discharge procedures at the end of the last period. Subjects will be called 3 to 5 days after discharge to inquire concerning Adverse Events (AEs) and concomitant medications since discharge.

Official Title
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An Open-Label, Three-Period, Three-Treatment, Six-Sequence, Randomized Crossover Study of the Pharmacokinetics of Intranasal Nalmefene in Healthy Volunteers Using Three Dosing Regimens

Conditions
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Opioid Overdose

Intervention / Treatment
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* Drug: Nalmefene Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18 to 55 years inclusive BMI ranging from 18 to 30 kg/m2, inclusive Adequate venous access Subjects must be non-smokers Exclusion Criteria: History of clinically significant disease Significant trauma injury, major surgery, open biopsy within 30 days prior to screening Following an abnormal diet 4 weeks prior to screening Use of over the counter medications, dietary supplements, herbal products, vitamins or opioid analgesics 14 days before intervention Use of enzyme altering drugs 30 days before intervention Use of nasal products 28 days before intervention and throughout the study Previous or current opioid, alcohol, or other drug dependence Donated or received blood 30 days before intervention Women who are pregnant or breastfeeding at screening Women of childbearing potential unless surgically sterile or use effective contraception Male subjects of childbearing potential that do not agree to use effective contraception Male subjects who plan to donate sperm or have female partner(s) who are pregnant, lactating or planning to attempt to become pregnant Current or recent upper respiratory tract infection Allergic to nalmefene

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Intranasal Nalmefene 1 spray in 1 nostril<br>Nalmefene Hydrochloride nasal spray, 3mg, 1 spray in 1 nostril | Drug: Nalmefene Hydrochloride<br>* 3mg nasal spray<br>|
| Experimental: Intranasal Nalmefene 2 sprays in 1 nostril<br>Nalmefene Hydrochloride nasal spray, 6mg, 2 sprays in 1 nostril | Drug: Nalmefene Hydrochloride<br>* 3mg nasal spray<br>|
| Experimental: Intranasal Nalmefene 1 spray in each nostril<br>Nalmefene Hydrochloride nasal spray, 6mg, 1 spray in each nostril | Drug: Nalmefene Hydrochloride<br>* 3mg nasal spray<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) | Maximum concentration of plasma nalmefene comparing 1 dose of IN in one nostril to 2 doses of IN in 1 nostril to 1 dose of IN in each nostril | 48 hours | 
| Time to maximum plasma concentration (Tmax) | Time to maximum concentration of plasma nalmefene comparing 1 dose of IN in one nostril to 2 doses of IN in 1 nostril to 1 dose of IN in each nostril | 48 hours | 
| Area under the curve (AUC) | Area under the curve of plasma nalmefene comparing 1 dose of IN in one nostril to 2 doses of IN in 1 nostril to 1 dose of IN in each nostril | 48 hours | 
| Half-life (t1/2) | Half life of plasma nalmefene comparing 1 dose of IN in one nostril to 2 doses of IN in 1 nostril to 1 dose of IN in each nostril | 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics