Comparison of Naloxone Pharmacokinetics

Comparison of Naloxone Pharmacokinetics Using Marketed Naloxone Devices

Intranasal (IN) naloxone administration is an effective alternative to intravenous (IV) or intramuscular (IM) naloxone by emergency medical services for opioid overdoses and has been used successfully for this purpose as reported in clinical observational studies and a randomized controlled trial. Most of the published clinical studies concerning IN administration used an improvised kit of 2 mg naloxone/2 mL saline and a mucosal atomizer device (MAD), which is not FDA-approved for this indication. Pharmacokinetic (PK) data using these kits is not available in the published literature. This study is designed to determine the PK of naloxone following one and two IN administrations using the improvised kits compared to 2 and 4 mg delivered IN using the FDA-approved Narcan nasal spray device and 2 mg administered IM using the Evzio autoinjector.

Study Overview

• Status: Completed
• Conditions: Opioid-use Disorder
• Intervention / Treatment: Drug: Naloxone; Device: Mucosal atomization device and syringe; Device: Narcan; Device: Intramuscular Auto Injector

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Vince and Associates Clinical Research

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:

• Males and females 18 to 55 years of age, inclusive
• Provide written informed consent
• BMI ranging from 18 to 32 kg/m2, inclusive
• Adequate venous access
• No clinically significant concurrent medical conditions determined by medical history, physical examination, clinical laboratory examination, vital signs, and 12-lead ECG
• Male subjects must agree to use an acceptable method of contraception with female partners as well as not to donate sperm from the screening visit until 90 days after the last study drug administration
• Female subjects of childbearing potential must agree to use an acceptable method of birth control from the start of screening until 30 days after the last study drug administration. Oral contraceptives are prohibited
• Agree not to ingest alcohol, drinks containing xanthine >500 mg/day (e.g., Coca Cola®, coffee, tea, etc.), or grapefruit/grapefruit juice or participate in strenuous exercise 72 hours prior to admission through the last blood draw of the study

Exclusion Criteria:

• Contact site directly for more information

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Mucosal Atomization (1 administration); One Intranasal administration of 2 mL naloxone using a mucosal atomization device and syringe (1 mL/nostril)	Drug: Naloxone; Comparing pharmacokinetics of naloxone; Device: Mucosal atomization device and syringe; Injection
Experimental: Mucosal Atomization (2 administrations); Two Intranasal administrations of 2 mL naloxone using mucosal atomization device and syringe (1 mL/nostril) 2 minutes apart	Drug: Naloxone; Comparing pharmacokinetics of naloxone; Device: Mucosal atomization device and syringe; Injection
Experimental: Narcan 2mg; One Intranasal administration of 2 mg naloxone using Narcan nasal spray	Drug: Naloxone; Comparing pharmacokinetics of naloxone; Device: Narcan; Nasal Spray
Experimental: Narcan 4mg; One Intranasal administration of 4 mg naloxone using Narcan nasal spray	Drug: Naloxone; Comparing pharmacokinetics of naloxone; Device: Narcan; Nasal Spray
Experimental: Intramuscular auto injector; One Intramuscular administration of 2 mg naloxone using Evzio auto-injector	Drug: Naloxone; Comparing pharmacokinetics of naloxone; Device: Intramuscular Auto Injector; Intramuscular injection; Other Names: Evzio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameters of naloxone	Maximum plasma concentration, time of maximum observed concentration and area under the concentration-time curve	11 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Assessments	Number of participants with AEs, vital signs, ECG, laboratory changes and nasal irritation following the administration of naloxone.	16 days

Collaborators and Investigators

• Sponsor: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Debra Kelsh, MD, Vince and Associates Clinical Research

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2018
• Primary Completion (Actual): February 8, 2018
• Study Completion (Actual): March 6, 2018

Study Registration Dates

• First Submitted: December 18, 2017
• First Submitted That Met QC Criteria: December 21, 2017
• First Posted (Actual): December 29, 2017

Study Record Updates

• Last Update Posted (Actual): March 9, 2018
• Last Update Submitted That Met QC Criteria: March 7, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Opioid-Related Disorders; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Naloxone
• Other Study ID Numbers: Naloxone P1a-003

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
• product manufactured in and exported from the U.S.: No