Pharmacokinetic Evaluation of Intranasal and Intramuscular Naloxone in Healthy Volunteers

Study Overview
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Brief Summary
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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.

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

Conditions
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Drug Overdose, Opioid-Related Disorders

Intervention / Treatment
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* Drug: Naloxone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |