Pharmacodynamic Evaluation of Intramuscular Nalmefene Autoinjector 1.5 mg Compared to Intranasal Narcan 4 mg

A Study to Characterize the Time Course of Reversal of Opioid (Fentanyl)-Induced Respiratory Depression Following Administration of Nalmefene Autoinjector 1.5 mg (0.94% MgCl2) Intramuscular and Narcan® 4 mg Intranasal in Healthy Subjects

The purpose of this study is to determine the pharmacodynamics (change in minute ventilation) of nalmefene when given as an autoinjector intramuscularly (IM; into the thigh) compared to naloxone when given intranasally (IN; into the nose) to healthy subjects with prior opioid exposure under steady state fentanyl concentrations (opioid agonism).

Study Overview

• Status: Completed
• Conditions: Opioid Overdose
• Intervention / Treatment: Drug: Nalmefene HCl injection; Drug: Naloxone HCl intranasal

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43212
      • Ohio Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria include:

1. Healthy and free of significant abnormal findings as determined by medical history, physical examination, clinical laboratory values, vital signs, and ECG.
2. Body weight ranging from 50 to 100 kg (110-220 lbs) and body mass index (BMI) within the range [18-30] kg/m2 (inclusive).
3. Willing to be compliant with the protocol, capable of subjective evaluation, if applicable, able to read and understand questionnaires, if applicable.

Key Exclusion Criteria include:

1. Females who are pregnant or lactating.
2. Any significant illness during the 30 days preceding the initial dose in this study.
3. History or any current conditions that might interfere with drug absorption, distribution, metabolism or excretion.
4. Refusal to abstain from caffeine or xanthine containing beverages entirely during confinement.
5. Refusal to abstain from consumption of alcoholic beverages 48 hours prior to initial study drug administration and through the end-of-study visit.
6. Difficulty with venous access or unsuitable for or unwilling to undergo catheter insertion.

Other inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nalmefene Hydrochloride (HCl) injection; Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration	Drug: Nalmefene HCl injection; Nalmefene Hydrochloride injection 1.5 mg for intramuscular (IM) administration
Active Comparator: Narcan intranasal; Naloxone 4 mg for intranasal (IN) administration	Drug: Naloxone HCl intranasal; Naloxone 4 mg for intranasal (IN) administration; Other Names: Narcan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Minute Ventilation 5 Minutes From Opioid Induced Nadir	To assess the change in minute ventilation at 5 minutes of intramuscular nalmefene and intranasal naloxone reversal from the opioid induced nadir.	5 minutes after opioid antagonist administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax)	Maximum plasma concentration of nalmefene and naloxone.	up to 24 hours post-dose
Area Under the Curve (AUCt)	Area under the plasma concentration-time curve from time zero to the time of last measurable concentration.	up to 24 hours post-dose
Area Under the Curve (AUCinf)	Area under the plasma concentration-time curve from time zero to infinity.	up to 24 hours post-dose
Time to Maximum Plasma Concentration (Tmax)	Time to maximum plasma concentration of nalmefene and naloxone.	up to 24 hours post-dose
Half-life (T1/2)	Half life of nalmefene and naloxone.	up to 24 hours post-dose
Change in Minute Ventilation at 2.5, 5, 10, 15, 20, 30, and 90 Minutes From Opioid Induced Nadir	To assess the time course of changes in minute ventilation of intramuscular nalmefene and intranasal naloxone reversal from the opioid induced nadir.	Baseline, 2.5, 5, 10, 15, 20, 30, and 90 minutes after opioid antagonist administration
Area Under the Curve (AUC0-2.5)	Area under the plasma concentration-time curve from time zero to 2.5 minutes	2.5 minutes post-dose
Area Under the Curve (AUC0-5)	Area under the plasma concentration-time curve from time zero to 5 minutes	5 minutes post-dose
Area Under the Curve (AUC0-10)	Area under the plasma concentration-time curve from time zero to 10 minutes	10 minutes post-dose
Area Under the Curve (AUC0-15)	Area under the plasma concentration-time curve from time zero to 15 minutes	15 minutes post-dose
Area Under the Curve (AUC0-20)	Area under the plasma concentration-time curve from time zero to 20 minutes	20 minutes post-dose
Time to First Measurable Plasma Concentration (Tlag)	Time to first measurable plasma concentration of nalmefene and naloxone.	up to 24 hours post-dose

Collaborators and Investigators

• Sponsor: Purdue Pharma LP

Study record dates

Study Major Dates

• Study Start (Actual): October 3, 2022
• Primary Completion (Actual): December 23, 2022
• Study Completion (Actual): December 23, 2022

Study Registration Dates

• First Submitted: December 2, 2024
• First Submitted That Met QC Criteria: December 2, 2024
• First Posted (Actual): December 6, 2024

Study Record Updates

• Last Update Posted (Actual): July 3, 2025
• Last Update Submitted That Met QC Criteria: June 16, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Narcotic-Related Disorders; Drug Misuse; Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Drug Overdose; Prescription Drug Misuse; Opioid-Related Disorders; Opiate Overdose; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Naloxone; Nalmefene
• Other Study ID Numbers: NAL1004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No