Study of Single and Multiple Doses of Inhaled AeroLEF (Liposome-Encapsulated Fentanyl)in Healthy Subjects

Study Overview
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Brief Summary
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This study was designed to assess single-dose and multiple-dose PK and safety parameters utilizing a dosage of 3 mL (500 µg/mL)AeroLEF delivered via nebulization with the AeroEclipse BAN device. The study was conducted in opioid naïve subjects who were not blocked with naloxone or other opioid receptor antagonists.

Detailed Description
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Period I: Subjects received an i.v.dose of fentanyl (200 µg) (Treatment A). Period II: Subjects were randomly assigned to receive either a single-dose (Treatment B) or multi-dose (Treatment C) of AeroLEF. In the multi-dose Treatment C group, subjects received a dose of 3 mL AeroLEF every 12 hours for a total of five doses over a 3 days with a 4 week washout period before crossing over to Period III. Period III: Subjects from Period II participated in the crossover study and receive either a multi-dose (Treatment C, 5 doses at 12 hour intervals) or a single dose (Treatment B). Subjects in Treatment B or Treatment C were instructed to continue inhalation of AeroLEF for approximately one (1) minute beyond the point of nebulizer sputter to ensure that all aerosolized medication was delivered.

Official Title
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Phase I, 3-Period, Fasting, Bioavailability, Safety Assessment and PK Study Evaluating Single Dose Administration of i.v. Fentanyl (200 µg) and Single and Multiple Doses of 3 mL of Inhaled AeroLEF (Liposome-Encapsulated Fentanyl 500 µg/mL) Administered in Normal Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: i.v. fentanyl
* Drug: 3 mL AeroLEF (500 µg/1 mL)
* Drug: 3 mL AeroLEF (500 µg/1 mL)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-smoking male or female with a minimum age of at least 18 years Body weight with aBMI range of 18.5 - 27, with a minimum weight of at least 60 kg. Availability of subject for the entire study period and willingness to adhere to protocol requirements, as evidenced by a signed, written, Informed Consent Form. Normal findings in the physical examination, vital signs (blood pressure between 100-140 - 60-90 mmHg, heart rate between 55-99 beats/min, respiration rate between 12-20 minute) and a 12 lead ECG. Negative for drug abuse, nicotine, alcohol, hepatitis B-surface antigen, hepatitis C and HIV. If a female of child-bearing potential, the patient must have a negative urine pregnancy test at screening and baseline. No clinical laboratory values outside of the Principal Investigator's acceptable range, unless the Principal Investigator decided that the subject's values are not clinically significant. Female subjects: (a) if pre-menopausal, have regular menstrual cycles (28-32 days), and (b) are not pregnant prior to study start and avoids pregnancy during the study and 1 month post drug administration, or (c) were surgically sterile for at least 6 months prior to enrollment, or (d) are post-menopausal for at least 1 year prior to enrollment. Exclusion Criteria: Known history of hypersensitivity to fentanyl. Presence or history of cardiac, pulmonary, gastrointestinal, endocrine, neuromuscular, neurologic, hematological, liver or kidney disease, or any condition known to interfere with absorption, distribution , metabolism, or excretion of drugs. History of drug abuse or narcotic dependency. Use of prescription medication within 30 days preceding entry int the study, including any enzyme inducing/inhibitory drugs (excluding contraceptives). Participating in a clinical trial with an investigational drug within 30 days preceding this trial. Blood donation within 45 days preceding this trial.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Active Comparator: Treatment Group A<br>Subjects received an i.v. dose of fentanyl (200 µg) | Drug: i.v. fentanyl<br>* single dose, 200 ug<br>* Other names: fetanyl citrate injection;|
| Experimental: Treatment Group B<br>Subjects received a single dose of 3 mL AeroLEF (500 µg/1 mL) | Drug: 3 mL AeroLEF (500 µg/1 mL)<br>* A single dose of 3mL (500 µg/1 mL) of AeroLEF (Aerosolized Free and Liposome-Encapsulated Fentanyl)<br>* Other names: Aerosolized Free and Liposome-Encapsulated Fentanyl;|
| Experimental: Treatment Group C<br>Subjects received multiple doses of 3 mL AeroLEF (500 µg/1 mL) every 12 hours for a total of five doses over a 3 days | Drug: 3 mL AeroLEF (500 µg/1 mL)<br>* A multiple doses of 3mL (500 µg/1 mL)of AeroLEF (Aerosolized Free and Liposome-Encapsulated Fentanyl)every 12 hours for a total of five doses over a 3 days<br>* Other names: Aerosolized Free and Liposome-Encapsulated Fentanyl;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events |  | continuously | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacokinetics and bioavailability |  | various time points | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AeroLEF, fentanyl, pharmacokinetics, liposome, encapsulated