Fentanyl Sublingual Spray and Fentanyl Citrate Intravenous (IV) in Opioid Naive Subjects

Study Overview
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Brief Summary
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The primary objective of this study is to determine the pharmacokinetic and pharmacodynamic relationship of a single dose of fentanyl sublingual spray in opioid naive subjects. The secondary objective is to determine the safety and tolerability of fentanyl sublingual spray in opioid naive subjects.

Official Title
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A Phase 1, Open-label, Randomized, Single Ascending Dose Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Fentanyl Sublingual Spray and Fentanyl Citrate Intravenous (IV) in Opioid Naive Subjects

Conditions
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Pharmacokinetics and Pharmacodynamics

Intervention / Treatment
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* Drug: Fentanyl
* Drug: Fentanyl Citrate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets protocol-specified criteria for qualification and contraception Willing and able to remain confined in the study unit for the entire duration of each treatment period and comply with restrictions related food, drink and medications Voluntarily consents to participate and provides written informed consent prior to any protocol-specific procedures Exclusion Criteria: History or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters Signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise: the safety or well-being of the participant or study staff the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding) the analysis of results

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>After a 10-hour fast, the 10 participants in this cohort are randomized to receive Fentanyl Sublingual (under the tongue) Spray (FSS) 100 mcg (n=8), or Fentanyl Citrate Intravenously (FCIV) 50 mcg (n=2). | Drug: Fentanyl<br>* Fentanyl Sublingual Spray (FSS)<br>Drug: Fentanyl Citrate<br>* Fentanyl Citrate IV (FCIV)<br>|
| Experimental: Cohort 2<br>After a 10-hour fast, the 10 participants in this cohort are randomized to receive FSS 200 mcg (n=8), or FCIV 50 mcg (n=2). | Drug: Fentanyl<br>* Fentanyl Sublingual Spray (FSS)<br>Drug: Fentanyl Citrate<br>* Fentanyl Citrate IV (FCIV)<br>|
| Experimental: Cohort 3<br>After a 10-hour fast, the 10 participants in this cohort are randomized to receive FSS 400 mcg (n=8), or FCIV 50 mcg (n=2). | Drug: Fentanyl<br>* Fentanyl Sublingual Spray (FSS)<br>Drug: Fentanyl Citrate<br>* Fentanyl Citrate IV (FCIV)<br>|
| Experimental: Cohort 4<br>After a 10-hour fast, the 10 participants in this cohort are randomized to receive FSS 600 mcg (n=8), or FCIV 50 mcg (n=2). | Drug: Fentanyl<br>* Fentanyl Sublingual Spray (FSS)<br>Drug: Fentanyl Citrate<br>* Fentanyl Citrate IV (FCIV)<br>|
| Experimental: Cohort 5<br>After a 10-hour fast, the 10 participants in this cohort are randomized to receive FSS 800 mcg (n=8), or FCIV 50 mcg (n=2). | Drug: Fentanyl<br>* Fentanyl Sublingual Spray (FSS)<br>Drug: Fentanyl Citrate<br>* Fentanyl Citrate IV (FCIV)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration |  | 0 (pre-dose), 5, 10, 20, 30 and 40 minutes after dosing and at 1, 1.25, 1.5, 2, 4, 6, 8, 10, 12, 16, and 24 hours after dosing | 
| Time to maximum concentration |  | 0 (pre-dose), 5, 10, 20, 30 and 40 minutes after dosing and at 1, 1.25, 1.5, 2, 4, 6, 8, 10, 12, 16, and 24 hours after dosing | 
| Area under the plasma concentration-time curve from 0 to the final time with a concentration at or above the limit of quantitation (LoQ) |  | 0 (pre-dose), 5, 10, 20, 30 and 40 minutes after dosing and at 1, 1.25, 1.5, 2, 4, 6, 8, 10, 12, 16, and 24 hours after dosing | 
| Area under the plasma concentration-time curve from 0 to infinity |  | 0 (pre-dose), 5, 10, 20, 30 and 40 minutes after dosing and at 1, 1.25, 1.5, 2, 4, 6, 8, 10, 12, 16, and 24 hours after dosing | 
| Apparent elimination rate constant in the terminal phase by noncompartmental analysis |  | 0 (pre-dose), 5, 10, 20, 30 and 40 minutes after dosing and at 1, 1.25, 1.5, 2, 4, 6, 8, 10, 12, 16, and 24 hours after dosing | 
| Elimination half-life |  | 0 (pre-dose), 5, 10, 20, 30 and 40 minutes after dosing and at 1, 1.25, 1.5, 2, 4, 6, 8, 10, 12, 16, and 24 hours after dosing | 
| Apparent oral clearance of drug following extravascular administration |  | 0 (pre-dose), 5, 10, 20, 30 and 40 minutes after dosing and at 1, 1.25, 1.5, 2, 4, 6, 8, 10, 12, 16, and 24 hours after dosing | 
| Volume of distribution during terminal phase following extravascular administration |  | 0 (pre-dose), 5, 10, 20, 30 and 40 minutes after dosing and at 1, 1.25, 1.5, 2, 4, 6, 8, 10, 12, 16, and 24 hours after dosing |