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

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

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.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Fentanyl 400 µg sublingual spray; Drug: Naltrexone 50 mg; Drug: Actiq® 400 µg transmucosally; Drug: Fentanyl citrate injection 100 µg intravenously

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fentanyl 400 µg sublingual spray + naltrexone 50 mg; Patients received a single administration of 400 µg of fentanyl spray sublingually + naltrexone hydrochloride 50 mg orally.	Drug: Fentanyl 400 µg sublingual spray; Drug: Naltrexone 50 mg; Naltrexone hydrochloride was administered approximately 12 hours and 1 hour prior to and 12 hours after each dose of fentanyl to minimize the occurrence of unacceptable adverse effects (eg, decreased respiration, nausea) often associated with administration of fentanyl.
Active Comparator: Actiq® 400 µg transmucosally + naltrexone 50 mg; Patients received a single administration of 400 µg of Actiq® transmucosally + naltrexone hydrochloride 50 mg orally.	Drug: Naltrexone 50 mg; Naltrexone hydrochloride was administered approximately 12 hours and 1 hour prior to and 12 hours after each dose of fentanyl to minimize the occurrence of unacceptable adverse effects (eg, decreased respiration, nausea) often associated with administration of fentanyl.; Drug: Actiq® 400 µg transmucosally; Actiq® 400 µg is a solid formulation of fentanyl citrate on a plastic stick that dissolves slowly in the mouth for absorption across the buccal mucosa.; Other Names: fentanyl citrate
Active Comparator: Fentanyl citrate injection 100 µg iv + naltrexone 50 mg; Patients received a single administration of 100 µg of fentanyl citrate intravenously + naltrexone hydrochloride 50 mg orally.	Drug: Naltrexone 50 mg; Naltrexone hydrochloride was administered approximately 12 hours and 1 hour prior to and 12 hours after each dose of fentanyl to minimize the occurrence of unacceptable adverse effects (eg, decreased respiration, nausea) often associated with administration of fentanyl.; Drug: Fentanyl citrate injection 100 µg intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to reach the maximum drug concentration (Tmax) in plasma	Up to 60 minutes pre-dose to 36 hours post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum drug concentration (Cmax) in plasma	Up to 60 minutes pre-dose to 36 hours post-dose
Area under the plasma concentration-time curve from time-0 to the time of the last quantifiable concentration (AUClast)	Up to 60 minutes pre-dose to 36 hours post-dose
Area under the plasma concentration-time curve from time-0 extrapolated to infinity (AUCinf)	Up to 60 minutes pre-dose to 36 hours post-dose
Percentage of AUCinf based on extrapolation (AUCextrap)	Up to 60 minutes pre-dose to 36 hours post-dose
Observed elimination rate constant (λz)	Up to 60 minutes pre-dose to 36 hours post-dose
Observed terminal elimination half-life (T1/2)	Up to 60 minutes pre-dose to 36 hours post-dose
Time of the last measurable concentration of drug (Tlast) in plasma	Up to 60 minutes pre-dose to 36 hours post-dose
Last quantifiable drug concentration (Clast) in plasma	Up to 60 minutes pre-dose to 36 hours post-dose

Collaborators and Investigators

• Sponsor: INSYS Therapeutics Inc
• Investigators: Study Director: Neha Parikh, INSYS Therapeutics Inc; Principal Investigator: Frederick A. Bieberdorf, MD, CEDRA Clinical Research

Publications and helpful links

General Publications

• Parikh N, Goskonda V, Chavan A, Dillaha L. Single-dose pharmacokinetics of fentanyl sublingual spray and oral transmucosal fentanyl citrate in healthy volunteers: a randomized crossover study. Clin Ther. 2013 Mar;35(3):236-43. doi: 10.1016/j.clinthera.2013.02.017.

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): May 1, 2007
• Study Completion (Actual): May 1, 2007

Study Registration Dates

• First Submitted: January 28, 2013
• First Submitted That Met QC Criteria: January 28, 2013
• First Posted (Estimate): January 31, 2013

Study Record Updates

• Last Update Posted (Estimate): January 31, 2013
• Last Update Submitted That Met QC Criteria: January 28, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Opioid; Narcotics; Adjuvants, Anesthesia; Narcotic Antagonists; Anticoagulants; Alcohol Deterrents; Chelating Agents; Sequestering Agents; Calcium Chelating Agents; Fentanyl; Naltrexone; Citric Acid; Sodium Citrate
• Other Study ID Numbers: INS-06-003