Pharmacodynamic Evaluation of Intranasal Nalmefene

Opiant Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Pharmacodynamic

Treatments: Drug: Naloxone hydrochloride; Drug: Nalmefene hydrochloride

Study type: Interventional

Funder types: Industry

Identifiers

NCT04828005

OPNT003-PD-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 84 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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84 participants in 2 patient groups

Intranasal Nalmefene

Experimental group

Description:

Nalmefene hydrochloride nasal spray, 3mg, 1 spray

Treatment:

Drug: Nalmefene hydrochloride

Intranasal Naloxone

Active Comparator group

Description:

Naloxone hydrochloride nasal spray, 4mg, 1 spray

Treatment:

Drug: Naloxone hydrochloride