Pharmacodynamic Evaluation of Intranasal Nalmefene

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

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.

Study Overview

• Status: Completed
• Conditions: Pharmacodynamic
• Intervention / Treatment: Drug: Nalmefene hydrochloride; Drug: Naloxone hydrochloride

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.

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • PRA Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intranasal Nalmefene; Nalmefene hydrochloride nasal spray, 3mg, 1 spray	Drug: Nalmefene hydrochloride; 3mg Nasal spray
Active Comparator: Intranasal Naloxone; Naloxone hydrochloride nasal spray, 4mg, 1 spray	Drug: Naloxone hydrochloride; 4mg Nasal Spray

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

Collaborators and Investigators

• Sponsor: Opiant Pharmaceuticals Inc

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2021
• Primary Completion (Actual): March 14, 2022
• Study Completion (Actual): March 14, 2022

Study Registration Dates

• First Submitted: March 30, 2021
• First Submitted That Met QC Criteria: March 30, 2021
• First Posted (Actual): April 1, 2021

Study Record Updates

• Last Update Posted (Estimate): December 9, 2022
• Last Update Submitted That Met QC Criteria: December 8, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Naloxone; Nalmefene
• Other Study ID Numbers: OPNT003-PD-001

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