Pharmacokinetic Evaluation of Intranasal Nalmefene Using Three Dosing Regimens

An Open-Label, Three-Period, Three-Treatment, Six-Sequence, Randomized Crossover Study of the Pharmacokinetics of Intranasal Nalmefene in Healthy Volunteers Using Three Dosing Regimens

This study is to compare the pharmacokinetics (how the body absorbs, breaks down and eliminates drug from your body) of nalmefene when given as a single dose intranasally (IN;into the nose), as a single dose in each nostril and as two doses in one nostrils; and to evaluate the safety and tolerability of nalmefene IN.

Study Overview

• Status: Completed
• Conditions: Opioid Overdose
• Intervention / Treatment: Drug: Nalmefene Hydrochloride

Detailed Description

Open-label, randomized, 3-period, 3-treatment, 6-sequence, ranodmised crossover study in 24 healthy volunteers. Subjects will be assigned to each of the 6 possible sequences. Each subject will receive 3 intranasal (IN) nalmefene doses:

• 3mg IN dose (one 0.1mL spray of a 30mg/mL solution in one nostril)
• 6mg IN dose (one 0.1mL spray of a 30mg/mL solution in each nostril)
• 6mg IN dose (two 0.1mL sprays of a 30mg/mL solution in one nostril)

There will be a 6 day washout period between doses. Screening can occur up to 28 days before admission, subjects will then stay in the inpatient facility for 16 days to complete the treatment phase of the study and will be discharged following completion of the discharge procedures at the end of the last period. Subjects will be called 3 to 5 days after discharge to inquire concerning Adverse Events (AEs) and concomitant medications since discharge.

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

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78217
      • Worldwide Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Male or female aged 18 to 55 years inclusive
• BMI ranging from 18 to 30 kg/m2, inclusive
• Adequate venous access
• Subjects must be non-smokers

• On screening and admission, the following standards had to be met before dosing and were permitted to be repeated once:

  • Systolic blood pressure: 140 mmHg or less and equal to or greater than 90 mmHg
  • Diastolic blood pressure: 90 mmHg or less and equal to or greater than 55 mmHg
  • Heart rate: 100 beats per minute (bpm) or less and equal to or greater than 40 bpm
  • Respiratory rate: 20 respirations per minute (rpm) or less and equal to or greater than 8 rpm

Exclusion Criteria:

• History of clinically significant disease
• Significant trauma injury, major surgery, open biopsy within 30 days prior to screening
• Following an abnormal diet 4 weeks prior to screening
• Use of prescribed or over the counter medications, dietary supplements, herbal products, vitamins or opioid analgesics 14 days before intervention and throughout the study
• Use of enzyme altering drugs 30 days before intervention or during the study
• Use of nasal products 28 days before intervention and throughout the study
• Experimental agents used at least 8 weeks prior to initial dosing for a period equivalent to 5 half-lives of the agent (whichever was longer).
• Positive urine drug test for alcohol, opioids, cocaine, methamphetamine, benzodiazepines, tetrahydrocannabinol (THC), barbiturates, or methadone at screening or admission.
• Previous or current opioid, alcohol, or other drug dependence (excluding nicotine and caffeine)
• Positive urine screen for cotinine (smoking and the use of tobacco products were not permitted for 4 weeks prior to the first dose of study drug and throughout the duration of the study).
• An ECG QTcF interval >450 msec for males and > or equal to 470 msec for females.
• Clinically significant concurrent medical conditions
• Donated or received blood 30 days before intervention
• Women who are pregnant or breastfeeding at screening and prior to each administration of study drug
• Women of childbearing potential unless surgically sterile or use effective contraception
• Male subjects of childbearing potential that do not agree to use effective contraception
• Male subjects who plan to donate sperm or have female partner(s) who are pregnant, lactating or planning to attempt to become pregnant during the study or within 4 weeks after completion of the study
• Positive test for HBsAg, HCVAb, or HIVAb at screening
• Current or recent upper respiratory tract infection
• Current or recent use of any decongestants
• Allergic to nalmefene
• Those who would not abstain from engaging in strenuous exercise during the inpatient stay of the study.
• Those who would not abstain from consuming poppy seed or similar opium derived food stuff during the study.
• Those who would not abstain from ingesting alcohol, drinks containing xanthine >500 mg/day (e.g., Coca Cola®, coffee, tea, etc.), or grapefruit/grapefruit juice 72 hours before initial dosing and throughout the duration of the study.
• Those deemed unlikely to be able to comply with the requirements of the protocol.
• Those with any laboratory tests from samples taken at screening considered clinically significant.
• Those with a known intolerance to continuous ECG lead adhesive exposure.
• Brief Smell Identification Test (BSIT) score < 5 at screening.
• Those with a known hypersensitivity reaction to plastic.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intranasal Nalmefene 1 Spray in 1 Nostril; 3 mg IN Nalmefene Hydrochloride dose (one 0.1 mL spray of a 30 mg/mL solution in one nostril)	Drug: Nalmefene Hydrochloride; 30 mg/mL solution
Experimental: Intranasal Nalmefene 2 Sprays in 1 Nostril; 6 mg IN Nalmefene Hydrochloride dose (two 0.1 mL sprays of a 30 mg/mL solution in one nostril)	Drug: Nalmefene Hydrochloride; 30 mg/mL solution
Experimental: Intranasal Nalmefene 1 Spray in Each Nostril; 6 mg IN Nalmefene Hydrochloride dose (one 0.1 mL spray of a 30 mg/mL solution in each nostril)	Drug: Nalmefene Hydrochloride; 30 mg/mL solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Half-life (t1/2)	Half life of plasma nalmefene comparing 1 dose of IN in one nostril to 2 doses of IN in 1 nostril to 1 dose of IN in each nostril	48 hours
Maximum Plasma Concentration (Cmax)	Maximum concentration of plasma nalmefene comparing 1 dose of IN in one nostril to 2 doses of IN in 1 nostril to 1 dose of IN in each nostril	48 hours
Time to Maximum Plasma Concentration (Tmax)	Time to maximum concentration of plasma nalmefene comparing 1 dose of IN in one nostril to 2 doses of IN in 1 nostril to 1 dose of IN in each nostril	48 hours
Area Under the Curve (AUC)	Area under the curve of plasma nalmefene comparing 1 dose of IN in one nostril to 2 doses of IN in 1 nostril to 1 dose of IN in each nostril	48 hours

Collaborators and Investigators

• Sponsor: Opiant Pharmaceuticals Inc
• Investigators: Principal Investigator: Ingela Danielsson, MD, Worldwide Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Actual): November 19, 2021
• Study Completion (Actual): November 22, 2021

Study Registration Dates

• First Submitted: January 21, 2022
• First Submitted That Met QC Criteria: January 21, 2022
• First Posted (Actual): February 2, 2022

Study Record Updates

• Last Update Posted (Actual): August 5, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Pharmacokinetics
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Drug Overdose; Prescription Drug Misuse; Drug Misuse; Opiate Overdose; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Nalmefene
• Other Study ID Numbers: OPNT003-PK-002

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