Exploratory Bioavailability of Fentanyl Sublingual Spray Under Fasting Conditions

Study Overview
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Brief Summary
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The objective of this study is to compare the rate of absorption and bioavailability of fentanyl sublingual spray 400 mcg to fentanyl citrate 100 mcg by intramuscular injection.

Official Title
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Single-Dose, Open-Label, Two-Period, Two-Treatment, Two-Sequence Crossover Exploratory Bioavailability Study of Subsys® (Fentanyl Sublingual Spray), 400 mcg, and Fentanyl Citrate Injection 2 mL x 0.05 mg/mL (Total Dose 100 mcg) Under Fasted Conditions

Conditions
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Bioavailability

Intervention / Treatment
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* Drug: Fentanyl Sublingual Spray (FSS)
* Drug: Fentanyl Citrate Injection (FCI)
* Drug: Naltrexone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets protocol-specified criteria for qualification and contraception Good access to veins on both sides 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: Intolerance to venipuncture or injections Presence or history of oral disease, irritation or piercings Allergy or adverse response to fentanyl, naltrexone, or related drugs Tattoos, scarring, or other skin abnormality at planned injection sites 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: 1) the safety or well-being of the participant or study staff; 2) the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding); 3) 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FSS first, then FCI<br>At each of two treatment visits participants fast for 10 hours before dosing, and receive naltrexone before and after dosing. Participants in this group receive a single dose of fentanyl sublingual spray (FSS) at the first visit. After a washout period of at least seven days, they receive a single intramuscular fentanyl citrate injection (FCI) at the second treatment visit. | Drug: Fentanyl Sublingual Spray (FSS)<br>* A single dose of fentanyl, 400 mcg per sublingual spray<br>* Other names: Subsys®;Drug: Fentanyl Citrate Injection (FCI)<br>* A single dose of fentanyl citrate, 100 mcg per intramuscular injection<br>Drug: Naltrexone<br>* Naltrexone is provided as a 50 mg tablet before and after product dosing to minimize unacceptable adverse effects of fentanyl.<br>|
| Experimental: FCI first, then FSS<br>At each of two treatment visits participants fast for 10 hours before dosing, and receive naltrexone before and after dosing. Participants in this group receive a single intramuscular fentanyl citrate injection (FCI) at the first visit. After a washout period of at least seven days, they receive a single dose of fentanyl sublingual spray (FSS) at the second treatment visit. | Drug: Fentanyl Sublingual Spray (FSS)<br>* A single dose of fentanyl, 400 mcg per sublingual spray<br>* Other names: Subsys®;Drug: Fentanyl Citrate Injection (FCI)<br>* A single dose of fentanyl citrate, 100 mcg per intramuscular injection<br>Drug: Naltrexone<br>* Naltrexone is provided as a 50 mg tablet before and after product dosing to minimize unacceptable adverse effects of fentanyl.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration (Cmax) by mode of administration |  | within 36 hours after dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve [AUC(last)] by mode of administration |  | prior to the intial dose, at 5, 10, 20, 30, and 40 minutes postdose, and at 1.0, 1.25, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, and 36 hours post-dose | 
| Area under the curve extrapolated to infinity [AUC(inf)] by mode of administration |  | prior to the intial dose, at 5, 10, 20, 30, and 40 minutes postdose, and at 1.0, 1.25, 1.5, 2.0, 4.0, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, and 36 hours post-dose |