Pharmacokinetic Evaluation of Intranasal Nalmefene

Study Overview
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Brief Summary
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This study is to determine the pharmacokinetics (how the body absorbs, breaks down and eliminates drug from your body) of nalmefene when given intranasally (IN;into the nose) compared to a dose of nalmefene when given intramuscularly (IM; into the muscle); to compare the blood levels of nalmefene when given IN to nalmefene when given IM; and to evaluate the safety and tolerability of nalmefene IN.

Detailed Description
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Open-label, randomized, 2-period, 2-treatment, 2-sequence, crossover study in 68 healthy volunteers. Subjects will be assigned to each of the 2 possible sequences. Each subject will receive 2 treatments during the 2 dosing periods: Intranasal (IN) dose of 3 mg nalmefene hydrochloride and intramuscular (IM) dose of 1.0 mg nalmefene, with a 4 day washout period between doses. Screening can occur up to 28 days before baseline admission, subjects will then stay in the inpatient facility for 7 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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Two-Period, Two-Treatment, Randomized Crossover Study of the Pharmacokinetics of Nalmefene by Intranasal and Intramuscular Administration in Healthy Volunteers

Conditions
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Pharmacokinetics

Intervention / Treatment
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* Drug: Nalmefene Hydrochloride
* Drug: Nalmefene


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 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<br>Nalmefene hydrochloride nasal spray, 3mg, 1 spray | Drug: Nalmefene Hydrochloride<br>* 3mg nasal spray<br>|
| Active Comparator: Intramuscular Nalmefene<br>Nalmefene injection, 1mg, 1 injection | Drug: Nalmefene<br>* 1mg intramuscular injection<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 IN to IM | 48 hours | 
| Time to maximum plasma concentration (Tmax) | Time to maximum concentration of plasma nalmefene comparing IN to IM | 48 hours | 
| Area under the curve (AUC) | Area under the curve of plasma nalmefene comparing IN to IM | 48 hours | 
| Half-life (t1/2) | Half life of plasma nalmefene comparing IN to IM | 48 hours |