Clinical trial NCT04828005: Pharmacodynamic Evaluation of Intranasal Nalmefene
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacodynamic
Lead sponsor: Opiant Pharmaceuticals Inc
Sponsor class: INDUSTRY
First posted: 2021-04-01
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Change in minute ventilation
timeFrame: 5 minutes
Secondary outcomes:
measure: Maximum change in minute ventilation
timeFrame: 90 minutes
measure: Time to maximum change in minute ventilation
timeFrame: 90 minutes
measure: Change in minute ventilation
timeFrame: 90 minutes
measure: Change in minute ventilation
timeFrame: 20 minutes
measure: Change in minute ventilation
timeFrame: 15 minutes
measure: Change in minute ventilation
timeFrame: 10 minutes
measure: Change in minute ventilation
timeFrame: 2.5 minutes
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: PRA Health Sciences
state: Utah
Study officials:
affiliation: PRA Health Sciences
name: Shawn Searle, MD
role: PRINCIPAL_INVESTIGATOR
References: