Pharmacokinetic Study of Fentanyl 400 µg Sublingual Spray, Actiq® 400 µg Transmucosally, and Fentanyl Citrate Injection 100 µg Intravenously (iv)

Condition(s) targeted: Pain

Intervention: Fentanyl 400 µg sublingual spray (Drug); Actiq® 400 µg transmucosally (Drug); Fentanyl citrate injection 100 µg intravenously (Drug); Naltrexone 50 mg (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: INSYS Therapeutics Inc

Official(s) and/or principal investigator(s):
Neha Parikh, Study Director, Affiliation: INSYS Therapeutics Inc
Frederick A. Bieberdorf, MD, Principal Investigator, Affiliation: CEDRA Clinical Research

The objective of this study was to compare the rate of absorption and bioavailability of fentanyl 400 µg sublingual spray, Actiq® 400 µg transmucosally, and fentanyl citrate injection 100 µg intravenously.

Official title: A Single-dose Crossover Study of Fentanyl Sublingual Spray 400 Mcg Versus Actiq® 400 Mcg Versus Fentanyl Citrate Injection (iv) 100 Mcg Under Fasted Conditions

Study design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Time to reach the maximum drug concentration (Tmax) in plasma

Secondary outcome:

Maximum drug concentration (Cmax) in plasma

Area under the plasma concentration-time curve from time-0 to the time of the last quantifiable concentration (AUClast)

Area under the plasma concentration-time curve from time-0 extrapolated to infinity (AUCinf)

Percentage of AUCinf based on extrapolation (AUCextrap)

Observed elimination rate constant (λz)

Observed terminal elimination half-life (T1/2)

Time of the last measurable concentration of drug (Tlast) in plasma

Last quantifiable drug concentration (Clast) in plasma

Detailed description: This was a Phase I, single-dose, open-label, randomized, 3-period, 3-treatment cross over study in which 21 healthy subjects received single doses of fentanyl 400 µg sublingual spray, Actiq® 400 µg transmucosally, and fentanyl citrate injection 100 µg intravenously following a 10-hour overnight fast. There was a 7 day washout period between treatments.

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Male or non-pregnant, non-breast-feeding female between the ages of 18-55 inclusive.

- Body Mass Index (BMI) between 18-30 kg/m^2, inclusive, and body weight of at least 60

kg (132 lbs).

- Subject was healthy according to the medical history, laboratory results, and

physical examination. Exclusion Criteria:

- Had a presence or history of clinically significant cardiovascular, pulmonary,

hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition which, in the opinion of the Investigator would jeopardize the safety of the subject or the validity of the study results.

- Had a clinically significant abnormal finding on the physical exam, medical history,

electrocardiogram (ECG), or clinical laboratory results at screening.

- Had a significant history of hypersensitivity to opioid analgesics, fentanyl or any

related products, naltrexone, or severe hypersensitivity reactions (like angioedema) to any drugs.

- Had a significantly abnormal diet during the 4 weeks preceding the first dose of

study medication.

- Had donated blood or plasma within 30 days prior to the first dose of study

medication or during the course of this study.

- Had participated in another clinical trial within 30 days prior to the first dose of

study medication or during the course of this study.

- Had used any over-the-counter (OTC) medication, including nutritional supplements,

within 7 days prior to the first dose of study medication or during the course of this study.

- Had used any prescription medication, except hormonal contraceptive or hormonal

replacement therapy, within 14 days prior to the first dose of study medication or during the course of this study.

- Had used enzyme altering drugs such as barbiturates, corticosteroids, phenothiazines,

cimetidine, carbamazepine, etc, within 30 days prior to the first dose of study medication or during the course of this study.

- Had used opioid analgesics within the last 30 days.

CEDRA Clinical Research, LLC, Austin, Texas 78759, United States

Starting date: April 2007
Last updated: January 28, 2013