Evaluation of Intranasal Naltrexone and Naloxone

Pharmacokinetic Evaluation of Intranasal Naltrexone and Naloxone Administered Separately and in Combination in Healthy Volunteers

This study will be to determine the pharmacokinetics of naltrexone and naloxone when administered via intranasal separately and in combination in healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Opioid-use Disorder
• Intervention / Treatment: Drug: Naltrexone; Drug: Naloxone; Drug: Naltrexol

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

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:

• Males and females 18 to 55 years of age, inclusive.
• Provide written informed consent.
• Body mass index (BMI) ranging from 18 to 30 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.
• 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.
• Agree not to ingest alcohol, drinks containing xanthine >500 mg/day (e.g., Coca Cola®, tea, coffee, 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 for more information

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Naltrexone; Subject received a single intranasal dose of 2 mg naltrexone for a total of 3 times in a 13 day period with a 4-day washout period between each does until all treatments were administered	Drug: Naltrexone; Intranasal spray; Other Names: Vivitrol
EXPERIMENTAL: Naloxone; Subject received a single intranasal dose of 4 mg naloxone for a total of 3 times in a 13 day period with a 4-day washout period between each does until all treatments were administered	Drug: Naloxone; Intranasal spray; Other Names: Narcan
EXPERIMENTAL: Naltrexol; Subject received a single intranasal dose of a combination of 2 mg naltrexone and 4 mg naloxone for a total of 3 times in a 13 day period with a 4-day washout period between each does until all treatments were administered	Drug: Naltrexol; Intranasal spray

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameter [maximum serum concentration - Cmax]	The primary endpoints of the study are the pharmacokinetic parameter, maximum serum concentration [Cmax], of naltrexone and naloxone when administered and in combination.	12 days
Pharmacokinetic parameter [area under the plasma concentration time curve - AUCO-t]	The primary endpoints of the study are the pharmacokinetic parameter, area under the plasma concentration time curve [AUCO-t] of naltrexone and naloxone when administered and in combination.	12 days
Pharmacokinetic parameter [area under the plasma concentration curve from zero to infinity - AUCO-inf]	The primary endpoints of the study are the pharmacokinetic parameter, area under the plasma concentration curve from zero to infinity [AUCO-inf] of naltrexone and naloxone when administered and in combination.	12 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	To assess and document any adverse events measures	15 days
Vital Sign - Heart Rate	To assess and document heart rate before and after intranasal dosing	12 days
Vital Sign - Blood pressure (diastolic)	To assess and document blood pressure (diastolic) before and after intranasal dosing	12 days
Vital Sign - Blood pressure (systolic)	To assess and document blood pressure (systolic) before and after intranasal dosing	12 days
Vital Sign - Respiration Rate	To assess and document respiration rate before and after intranasal dosing	12 days
Electrocardiogram	Twelve-lead ECGs performed according to standard procedures that will assess P wave, PR interval, QRS complex, ST segment, T wave and QT interval.	12 days

Collaborators and Investigators

• Sponsor: National Institute on Drug Abuse (NIDA)
• Investigators: Study Chair: Nora Chiang, PhD, NIH / NIDA

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 5, 2015
• Primary Completion (ACTUAL): November 7, 2015
• Study Completion (ACTUAL): November 7, 2015

Study Registration Dates

• First Submitted: February 19, 2019
• First Submitted That Met QC Criteria: February 20, 2019
• First Posted (ACTUAL): February 22, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 14, 2020
• Last Update Submitted That Met QC Criteria: September 11, 2020
• Last Verified: February 1, 2019

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; Alcohol Deterrents; Naltrexone; Naloxone
• Other Study ID Numbers: Naltrexone-Ph1a-001

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