Comparison of Naloxone Pharmacokinetics

Study Overview
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Brief Summary
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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.

Official Title
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Comparison of Naloxone Pharmacokinetics Using Marketed Naloxone Devices

Conditions
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Opioid-use Disorder

Intervention / Treatment
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* Drug: Naloxone
* Device: Mucosal atomization device and syringe
* Device: Narcan
* Device: Intramuscular Auto Injector


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: Contact 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
Interventional Model Description: This will be an inpatient open-label, randomized, 5-period, 5-treatment, 5-sequence, crossover study involving approximately 30 healthy subjects.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mucosal Atomization (1 administration)<br>One Intranasal administration of 2 mL naloxone using a mucosal atomization device and syringe (1 mL/nostril) | Drug: Naloxone<br>* Comparing pharmacokinetics of naloxone<br>Device: Mucosal atomization device and syringe<br>* Injection<br>|
| Experimental: Mucosal Atomization (2 administrations)<br>Two Intranasal administrations of 2 mL naloxone using mucosal atomization device and syringe (1 mL/nostril) 2 minutes apart | Drug: Naloxone<br>* Comparing pharmacokinetics of naloxone<br>Device: Mucosal atomization device and syringe<br>* Injection<br>|
| Experimental: Narcan 2mg<br>One Intranasal administration of 2 mg naloxone using Narcan nasal spray | Drug: Naloxone<br>* Comparing pharmacokinetics of naloxone<br>Device: Narcan<br>* Nasal Spray<br>|
| Experimental: Narcan 4mg<br>One Intranasal administration of 4 mg naloxone using Narcan nasal spray | Drug: Naloxone<br>* Comparing pharmacokinetics of naloxone<br>Device: Narcan<br>* Nasal Spray<br>|
| Experimental: Intramuscular auto injector<br>One Intramuscular administration of 2 mg naloxone using Evzio auto-injector | Drug: Naloxone<br>* Comparing pharmacokinetics of naloxone<br>Device: Intramuscular Auto Injector<br>* Intramuscular injection<br>* Other names: Evzio;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters of naloxone | Maximum plasma concentration, time of maximum observed concentration and area under the concentration-time curve | 11 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Assessments | Number of participants with AEs, vital signs, ECG, laboratory changes and nasal irritation following the administration of naloxone. | 16 days |