Pharmacokinetic Evaluation of Intranasal and Intramuscular Naloxone in Healthy Volunteers

• Sponsor: National Institute on Drug Abuse (NIDA) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT02572089
• Collaborator: Vince & Associates Clinical Research, Inc. (Other)
• Enrollment: 30
• Location: 1
• Arms: 5
• Duration (Months): 3
• Patients Per Site Per Month: 9.9

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Drug Overdose; Opioid-Related Disorders	Drug: Naloxone	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1, Pharmacokinetic Evaluation of Intranasal and Intramuscular Naloxone in Healthy Volunteers
• Study Start Date: Oct 1, 2014
• Actual Primary Completion Date: Jan 1, 2015
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Maximum Plasma Concentration (Cmax) [720 minutes]

   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.

2. Time at Maximum Plasma Concentration (Tmax) [720 minutes]

   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

3. Area Under the Concentration (AUC 0-t) [720 minutes]

   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

4. Area Under Curve (AUC 0-inf) [720 minutes]

   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

5. Half-life [720 minutes]

   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

Secondary Outcome Measures

1. Adverse events [minimum of 18 days]

   will be reported from the start of the first session to the follow-up visit

2. Vital Signs [480 minutes]

   Measured at pre-dose and at times 30 , 60, 120 and 480 minutes after naloxone administration.

3. 12-lead electrocardiogram [480 minutes]

   Measured at pre-dose and at times 60 and 480 minutes after naloxone administration.

4. Nasal Irritation Scoring [24 hours]

   Measured at pre-dose and at times 5, 30 , 60, 240 minutes and 24 hours after nasal naloxone administration.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vince Associates Clinical Research	Overland Park	Kansas	United States	66212

Sponsors and Collaborators

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

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Institute on Drug Abuse (NIDA)
• ClinicalTrials.gov Identifier: NCT02572089
• Other Study ID Numbers: Naloxone-Phase1a-002
• First Posted: Oct 8, 2015
• Last Update Posted: Jan 12, 2017
• Last Verified: Oct 1, 2015

• Additional relevant MeSH terms: Opioid-Related Disorders; Drug Overdose; Naloxone

Study Results

No Results Posted as of Jan 12, 2017