Pharmacodynamic Evaluation of Intranasal Nalmefene

Study Overview
=================
Brief Summary
-----------------
This study is to determine the pharmacodynamics (the effects of the drug and mechanisms of their action within the body) of Nalmefene when given intranasally (IN; into the nose) compared to intranasal naloxone when given to healthy volunteers under steady state opioid agonism.

Detailed Description
-----------------
Open-label, 2-part study. Part 1 is a pilot study to determine the relationship between opioid agonism and suppression of carbon dioxide induced increases in minute ventilation prior to opioid exposure. Part 2 will be a randomized, 2 period, 2 treatment, crossover study to evaluate the pharmacodynamic effects of intranasal (IN) nalmefene compared to IN naloxone to reverse opioid-induced suppression of carbon dioxide induced increases in minute ventilation, in healthy volunteers with prior opioid exposure. Both Part 1 and Part 2 of the study will consist of an outpatient Screening Visit taking place 28 days prior to admission, an in-clinic Treatment Phase consisting of a 6 or 7 day inpatient stay, and a Follow-Up Phone Call conducted 3 to 7 days after discharge.

Official Title
-----------------
A Two-part Open Label Study of the Pharmacodynamic Effects of Intranasal Nalmefene Compared to Intranasal Naloxone in Healthy Volunteers Under Steady State Opioid Agonism

Conditions
-----------------
Pharmacodynamic

Intervention / Treatment
-----------------
* Drug: Nalmefene hydrochloride
* Drug: Naloxone hydrochloride


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female aged 18 to 55 years inclusive BMI ranging from 18 to 32 kg/m2, inclusive Adequate venous access Healthy subjects and non-dependent who are non dependent opioid experienced users, opioid experience defined as exposure to an opioid on at least 1 occasion prior to screening Exclusion Criteria: History of clinically significant disease Significant trauma injury, major surgery, open biopsy within 30 days prior to screening Subject who has a difficult airway for intubation. 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 or naloxone or known hypersensitivity reaction to plastics.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

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: Intranasal Naloxone<br>Naloxone hydrochloride nasal spray, 4mg, 1 spray | Drug: Naloxone hydrochloride<br>* 4mg Nasal Spray<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in minute ventilation | Change in minute ventilation from opioid induced nadir | 5 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum change in minute ventilation | Maximum change in minute ventilation from opioid induced nadir | 90 minutes | 
| Time to maximum change in minute ventilation | Time to maximum change in minute ventilation from opioid induced nadir | 90 minutes | 
| Change in minute ventilation | Change in minute ventilation from opioid induced nadir | 90 minutes | 
| Change in minute ventilation | Change in minute ventilation from opioid induced nadir | 20 minutes | 
| Change in minute ventilation | Change in minute ventilation from opioid induced nadir | 15 minutes | 
| Change in minute ventilation | Change in minute ventilation from opioid induced nadir | 10 minutes | 
| Change in minute ventilation | Change in minute ventilation from opioid induced nadir | 2.5 minutes |