Comparison of Naloxone Pharmacokinetics

NCT03386591 | Completed Phase 1 FDA Drug

• 1 other identifier: Naloxone P1a-003
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Opioid-use Disorder

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetic parameters of naloxone

  Maximum plasma concentration, time of maximum observed concentration and area under the concentration-time curve

  11 days

Secondary Outcomes (1)

• Safety Assessments

  16 days

Study Arms (5)

Mucosal Atomization (1 administration)

EXPERIMENTAL

One Intranasal administration of 2 mL naloxone using a mucosal atomization device and syringe (1 mL/nostril)

Drug: Naloxone; Device: Mucosal atomization device and syringe

Mucosal Atomization (2 administrations)

EXPERIMENTAL

Two Intranasal administrations of 2 mL naloxone using mucosal atomization device and syringe (1 mL/nostril) 2 minutes apart

Drug: Naloxone; Device: Mucosal atomization device and syringe

Narcan 2mg

EXPERIMENTAL

One Intranasal administration of 2 mg naloxone using Narcan nasal spray

Drug: Naloxone; Device: Narcan

Narcan 4mg

EXPERIMENTAL

One Intranasal administration of 4 mg naloxone using Narcan nasal spray

Drug: Naloxone; Device: Narcan

Intramuscular auto injector

EXPERIMENTAL

One Intramuscular administration of 2 mg naloxone using Evzio auto-injector

Drug: Naloxone; Device: Intramuscular Auto Injector

Interventions

Naloxone DRUG

Comparing pharmacokinetics of naloxone

Intramuscular auto injector; Mucosal Atomization (1 administration); Mucosal Atomization (2 administrations); Narcan 2mg; Narcan 4mg

Mucosal atomization device and syringe DEVICE

Injection

Mucosal Atomization (1 administration); Mucosal Atomization (2 administrations)

Narcan DEVICE

Nasal Spray

Narcan 2mg; Narcan 4mg

Intramuscular Auto Injector DEVICE

Intramuscular injection

Also known as: Evzio

Intramuscular auto injector

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• Contact site directly for more information

Sponsors & Collaborators

• National Institute on Drug Abuse (NIDA): lead

Study Sites (1)

Vince and Associates Clinical Research

Overland Park, Kansas, 66212, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Naloxone; Syringes

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Equipment and Supplies

Study Officials

• Debra Kelsh, MD

  Vince and Associates Clinical Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: This will be an inpatient open-label, randomized, 5-period, 5-treatment, 5-sequence, crossover study involving approximately 30 healthy subjects.

Study Record Dates

• First Submitted: December 18, 2017
• First Posted: December 29, 2017
• Study Start: January 3, 2018
• Primary Completion: February 8, 2018
• Study Completion: March 6, 2018
• Last Updated: March 9, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)