Pharmacodynamic Evaluation of Intranasal Nalmefene

Phase 1

Completed

• Conditions: Pharmacodynamic
• Interventions: Drug: Nalmefene hydrochloride; Drug: Naloxone hydrochloride

• Registration Number: NCT04828005
• Lead Sponsor: Opiant Pharmaceuticals Inc

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.

Study Timeline

• Study Start: 2021-03-30
• Study First Submitted: 2021-03-30
• Study First Submitted QC: 2021-03-30
• Study First Posted: 2021-04-01
• Primary Completion: 2022-03-14
• Study Completion: 2022-03-14
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-08
• Last Update Posted: 2022-12-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 84

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Intranasal Nalmefene	Nalmefene hydrochloride	Nalmefene hydrochloride nasal spray, 3mg, 1 spray
Intranasal Naloxone	Naloxone hydrochloride	Naloxone hydrochloride nasal spray, 4mg, 1 spray

Primary Outcome Measures

Name	Time	Method
Change in minute ventilation	5 minutes	Change in minute ventilation from opioid induced nadir

Secondary Outcome Measures

Name	Time	Method
Change in minute ventilation	2.5 minutes	Change in minute ventilation from opioid induced nadir
Maximum change in minute ventilation	90 minutes	Maximum change in minute ventilation from opioid induced nadir
Time to maximum change in minute ventilation	90 minutes	Time to maximum change in minute ventilation from opioid induced nadir

Trial Locations

Locations (1)

PRA Health Sciences; 🇺🇸 Salt Lake City, Utah, United States