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

Purpose

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.

Condition	Intervention	Phase
Pain	Drug: Fentanyl 400 µg sublingual spray Drug: Actiq® 400 µg transmucosally Drug: Fentanyl citrate injection 100 µg intravenously Drug: Naltrexone 50 mg	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

Drug Information available for: Fentanyl Fentanyl citrate Sodium citrate Naltrexone Naltrexone hydrochloride

U.S. FDA Resources

Further study details as provided by Insys Therapeutics Inc:

Primary Outcome Measures:

Time to reach the maximum drug concentration (Tmax) in plasma [ Time Frame: Up to 60 minutes pre-dose to 36 hours post-dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Maximum drug concentration (Cmax) in plasma [ Time Frame: Up to 60 minutes pre-dose to 36 hours post-dose ] [ Designated as safety issue: No ]
Area under the plasma concentration-time curve from time-0 to the time of the last quantifiable concentration (AUClast) [ Time Frame: Up to 60 minutes pre-dose to 36 hours post-dose ] [ Designated as safety issue: No ]
Area under the plasma concentration-time curve from time-0 extrapolated to infinity (AUCinf) [ Time Frame: Up to 60 minutes pre-dose to 36 hours post-dose ] [ Designated as safety issue: No ]
Percentage of AUCinf based on extrapolation (AUCextrap) [ Time Frame: Up to 60 minutes pre-dose to 36 hours post-dose ] [ Designated as safety issue: No ]
Observed elimination rate constant (λz) [ Time Frame: Up to 60 minutes pre-dose to 36 hours post-dose ] [ Designated as safety issue: No ]
Observed terminal elimination half-life (T1/2) [ Time Frame: Up to 60 minutes pre-dose to 36 hours post-dose ] [ Designated as safety issue: No ]
Time of the last measurable concentration of drug (Tlast) in plasma [ Time Frame: Up to 60 minutes pre-dose to 36 hours post-dose ] [ Designated as safety issue: No ]
Last quantifiable drug concentration (Clast) in plasma [ Time Frame: Up to 60 minutes pre-dose to 36 hours post-dose ] [ Designated as safety issue: No ]

Enrollment:	40
Study Start Date:	April 2007
Study Completion Date:	May 2007
Primary Completion Date:	May 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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: 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 Name: fentanyl citrate 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: 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: Fentanyl citrate injection 100 µg intravenously 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.

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.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01780233

Locations

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

Sponsors and Collaborators

Insys Therapeutics Inc

Investigators

Study Director:	Neha Parikh	Insys Therapeutics Inc
Principal Investigator:	Frederick A. Bieberdorf, MD	CEDRA Clinical Research

More Information

No publications provided by Insys Therapeutics Inc

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Insys Therapeutics Inc
ClinicalTrials.gov Identifier:	NCT01780233 History of Changes
Other Study ID Numbers:	INS-06-003
Study First Received:	January 28, 2013
Last Updated:	January 28, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Citric Acid
Naltrexone
Fentanyl
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Chelating Agents
Molecular Mechanisms of Pharmacological Action
Narcotic Antagonists
Physiological Effects of Drugs

Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Adjuvants, Anesthesia
Narcotics
Central Nervous System Depressants
Analgesics
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Analgesics, Opioid

ClinicalTrials.gov processed this record on May 22, 2013