Pharmacokinetic Evaluation of Intranasal and Intramuscular Naloxone in Healthy Volunteers

Phase 1, Pharmacokinetic Evaluation of Intranasal and Intramuscular Naloxone in Healthy Volunteers

To determine the pharmacokinetics of 4 intranasal doses of naloxone compared to a 0.4 mg dose of naloxone administrated intramuscular and to identify an appropriate intranasal dose that could achieve systemic exposure comparable to an approved parenteral dose. To also determine the pharmacokinetics of two different concentrations of intranasal naloxone and finally, to determine the safety of intranasal naloxone with respect to nasal irritation.

Study Overview

• Status: Completed
• Conditions: Opioid-Related Disorders; Drug Overdose
• Intervention / Treatment: Drug: Naloxone

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

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Be able to provide written consent
• Must have a BMI ranging from 18 to 30kg/m2, inclusive
• Must have adequate venous access
• Must not have any clinically significant concurrent medical conditions determine by medical history, physical examination, vital signs, and 12-lead electrocardiogram.
• Must agree to use a reliable double-barrier method of birth control from the start of screening until one week after completing the study. Oral contraceptives are prohibited.
• Must agree to not ingest alcohol, drinks containing xanthine greater than 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:

• Please contact clinical site directly for more information

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2mg Intranasal Naloxone; Administer 0.1mL spray of the 20 mg/mL formulation in one nostril	Drug: Naloxone
Experimental: 4mg(a) Intranasal Naloxone; Administer 0.1mL spray of the 20 mg/mL formulation in both nostrils	Drug: Naloxone
Experimental: 4mg(b) Intranasal Naloxone; Administer 0.1mL spray of the 40mg/mL formulation in one nostril	Drug: Naloxone
Experimental: 8mg Intranasal Naloxone; Administer 0.1mL spray of the 40mg/mL formulation in both nostrils	Drug: Naloxone
Experimental: Intramuscular Naloxone; Administer 1mL of 0.4mg/mL formulation intramuscularly	Drug: Naloxone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax)	Measurement of serum naloxone prior to dosing and at times 2.5, 5, 10, 15, 20, 30, 45, 60, 120, 180, 240, 300, 360, 480 and 720 minutes after naloxone administration.	720 minutes
Time at Maximum Plasma Concentration (Tmax)	Measurement of serum naloxone prior to dosing and at times 2.5, 5, 10, 15, 20, 30, 45, 60, 120, 180, 240, 300, 360, 480 and 720 minutes after naloxone administration	720 minutes
Area Under the Concentration (AUC 0-t)	Time curve from time zero to last measurable concentration. Measurement of serum naloxone prior to dosing and at times 2.5, 5, 10, 15, 20, 30, 45, 60, 120, 180, 240, 300, 360, 480 and 720 minutes after naloxone administration	720 minutes
Area Under Curve (AUC 0-inf)	Time curve from time zero to infinity. Measurement of serum naloxone prior to dosing and at times 2.5, 5, 10, 15, 20, 30, 45, 60, 120, 180, 240, 300, 360, 480 and 720 minutes after naloxone administration	720 minutes
Half-life	The apparent terminal exponential half-life. Measurement of serum naloxone prior to dosing and at times 2.5, 5, 10, 15, 20, 30, 45, 60, 120, 180, 240, 300, 360, 480 and 720 minutes after naloxone administration	720 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	will be reported from the start of the first session to the follow-up visit	minimum of 18 days
Vital Signs	Measured at pre-dose and at times 30 , 60, 120 and 480 minutes after naloxone administration.	480 minutes
12-lead electrocardiogram	Measured at pre-dose and at times 60 and 480 minutes after naloxone administration.	480 minutes
Nasal Irritation Scoring	Measured at pre-dose and at times 5, 30 , 60, 240 minutes and 24 hours after nasal naloxone administration.	24 hours

Collaborators and Investigators

• Sponsor: National Institute on Drug Abuse (NIDA)
• Collaborators: Vince & Associates Clinical Research, Inc.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: October 5, 2015
• First Submitted That Met QC Criteria: October 6, 2015
• First Posted (Estimate): October 8, 2015

Study Record Updates

• Last Update Posted (Estimate): January 12, 2017
• Last Update Submitted That Met QC Criteria: January 11, 2017
• Last Verified: October 1, 2015

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; Drug Overdose; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Narcotic Antagonists; Naloxone
• Other Study ID Numbers: Naloxone-Phase1a-002