Do Furanocoumarins Mediate the Fexofenadine-grapefruit Juice Interaction?

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mary F. Paine, PhD, RPh, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT01526213
First received: January 31, 2012
Last updated: December 29, 2012
Last verified: December 2012
  Purpose

Purpose: Grapefruit juice is one of the most extensively studied dietary/natural substances shown to interact with a variety of medications. However, unanswered questions remain regarding the causative ingredients and mechanisms underlying such drug-grapefruit juice interactions. Compounds in grapefruit juice called furanocoumarins have been established as major causative ingredients, which act by inhibiting the elimination (metabolism) of drugs, leading to increased circulating drug concentrations. Increased drug concentrations can in turn lead to increased drug potency or even toxicity. Grapefruit juice also has been shown, paradoxically, to decrease circulating concentrations of some drugs, including the non-sedating antihistamine agent, fexofenadine (Allegra), which undergoes negligible metabolism. Whether or not furanocoumarins mediate the decrease in fexofenadine concentrations is unknown. The purpose of the proposed study is to compare the effects of a "furanocoumarin-free" grapefruit juice with grapefruit juice on circulating concentrations of fexofenadine.


Condition Intervention
Food-drug Interaction
Drug: Fexofenadine

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: Do Furanocoumarins Mediate the Fexofenadine-grapefruit Juice Interaction?

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Primary Pharmacokinetic Measure: Area Under the Curve (AUC) [ Time Frame: 0-72 hours ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: September 2009
Study Completion Date: April 2011
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sequence 1: Water, GFJ, FC-free GFJ
This randomized, open-label, single-dose, 3-way crossover study in healthy volunteers will be conducted in the CTRC. Once subjects are identified as eligible to participate, based on their screening evaluation and according to inclusion/exclusion criteria, they will undergo 3 phases. By randomized crossover design, the subject will receive fexofenadine with water, grapefruit juice (GFJ), or furanocoumarin (FC)-free grapefruit juice.
Drug: Fexofenadine
This randomized, open-label, single-dose, 3-way crossover study in healthy volunteers will be conducted in the CTRC. Once subjects are identified as eligible to participate, based on their screening evaluation and according to inclusion/exclusion criteria, they will undergo 3 phases. By randomized crossover design, the subject will receive fexofenadine with water, grapefruit juice, or furanocoumarin-free grapefruit juice.
Other Names:
  • Screening: labs, physical exam
  • Placement of an intravenous (IV) line
  • Collection of blood over 72 hours
Sequence 2: Water, FC-free GFJ, GFJ
This randomized, open-label, single-dose, 3-way crossover study in healthy volunteers will be conducted in the CTRC. Once subjects are identified as eligible to participate, based on their screening evaluation and according to inclusion/exclusion criteria, they will undergo 3 phases. By randomized crossover design, the subject will receive fexofenadine with water, grapefruit juice (GFJ), or furanocoumarin (FC)-free grapefruit juice.
Drug: Fexofenadine
This randomized, open-label, single-dose, 3-way crossover study in healthy volunteers will be conducted in the CTRC. Once subjects are identified as eligible to participate, based on their screening evaluation and according to inclusion/exclusion criteria, they will undergo 3 phases. By randomized crossover design, the subject will receive fexofenadine with water, grapefruit juice, or furanocoumarin-free grapefruit juice.
Other Names:
  • Screening: labs, physical exam
  • Placement of an intravenous (IV) line
  • Collection of blood over 72 hours
Sequence 3: GFJ, FC-free GFJ, Water
This randomized, open-label, single-dose, 3-way crossover study in healthy volunteers will be conducted in the CTRC. Once subjects are identified as eligible to participate, based on their screening evaluation and according to inclusion/exclusion criteria, they will undergo 3 phases. By randomized crossover design, the subject will receive fexofenadine with water, grapefruit juice (GFJ), or furanocoumarin (FC)-free grapefruit juice.
Drug: Fexofenadine
This randomized, open-label, single-dose, 3-way crossover study in healthy volunteers will be conducted in the CTRC. Once subjects are identified as eligible to participate, based on their screening evaluation and according to inclusion/exclusion criteria, they will undergo 3 phases. By randomized crossover design, the subject will receive fexofenadine with water, grapefruit juice, or furanocoumarin-free grapefruit juice.
Other Names:
  • Screening: labs, physical exam
  • Placement of an intravenous (IV) line
  • Collection of blood over 72 hours
Sequence 4: GFJ, Water, FC-free GFJ
This randomized, open-label, single-dose, 3-way crossover study in healthy volunteers will be conducted in the CTRC. Once subjects are identified as eligible to participate, based on their screening evaluation and according to inclusion/exclusion criteria, they will undergo 3 phases. By randomized crossover design, the subject will receive fexofenadine with water, grapefruit juice (GFJ), or furanocoumarin (FC)-free grapefruit juice.
Drug: Fexofenadine
This randomized, open-label, single-dose, 3-way crossover study in healthy volunteers will be conducted in the CTRC. Once subjects are identified as eligible to participate, based on their screening evaluation and according to inclusion/exclusion criteria, they will undergo 3 phases. By randomized crossover design, the subject will receive fexofenadine with water, grapefruit juice, or furanocoumarin-free grapefruit juice.
Other Names:
  • Screening: labs, physical exam
  • Placement of an intravenous (IV) line
  • Collection of blood over 72 hours
Sequence 5: FC-free GFJ, GFJ, Water
This randomized, open-label, single-dose, 3-way crossover study in healthy volunteers will be conducted in the CTRC. Once subjects are identified as eligible to participate, based on their screening evaluation and according to inclusion/exclusion criteria, they will undergo 3 phases. By randomized crossover design, the subject will receive fexofenadine with water, grapefruit juice (GFJ), or furanocoumarin (FC)-free grapefruit juice.
Drug: Fexofenadine
This randomized, open-label, single-dose, 3-way crossover study in healthy volunteers will be conducted in the CTRC. Once subjects are identified as eligible to participate, based on their screening evaluation and according to inclusion/exclusion criteria, they will undergo 3 phases. By randomized crossover design, the subject will receive fexofenadine with water, grapefruit juice, or furanocoumarin-free grapefruit juice.
Other Names:
  • Screening: labs, physical exam
  • Placement of an intravenous (IV) line
  • Collection of blood over 72 hours
Sequence 6: FC-free GFJ, Water, GFJ
This randomized, open-label, single-dose, 3-way crossover study in healthy volunteers will be conducted in the CTRC. Once subjects are identified as eligible to participate, based on their screening evaluation and according to inclusion/exclusion criteria, they will undergo 3 phases. By randomized crossover design, the subject will receive fexofenadine with water, grapefruit juice (GFJ), or furanocoumarin (FC)-free grapefruit juice.
Drug: Fexofenadine
This randomized, open-label, single-dose, 3-way crossover study in healthy volunteers will be conducted in the CTRC. Once subjects are identified as eligible to participate, based on their screening evaluation and according to inclusion/exclusion criteria, they will undergo 3 phases. By randomized crossover design, the subject will receive fexofenadine with water, grapefruit juice, or furanocoumarin-free grapefruit juice.
Other Names:
  • Screening: labs, physical exam
  • Placement of an intravenous (IV) line
  • Collection of blood over 72 hours

Detailed Description:

Participants: Healthy volunteers of any race/ethnicity, ranging in age from 18 to 65 years, will be enrolled.

Procedures (methods): Procedures will include administration of water, furanocoumarin-free grapefruit juice, or grapefruit juice with fexofenadine; placement of an intravenous (IV) line; and collection of blood over 72 hours.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men or women between the ages of 18 and 65
  • Normal screening laboratory test results
  • Able to understand the informed consent form
  • Willing to abstain from grapefruit products and all fruit juices for one week prior to and during the study
  • Willing to abstain from alcohol and caffeinated beverages the evening prior to each study day

Exclusion Criteria:

  • History of intolerance to grapefruit products
  • History of any allergy or hypersensitivity to grapefruit products or fexofenadine
  • History of significant medical conditions that the study physician believes would increase risk
  • History of significant alcohol abuse and/or illicit drug use
  • Tobacco use within the month preceding the study
  • Pregnancy or breast-feeding
  • Taking concomitant medications, both prescription and non-prescription (including herbal products), known to alter fexofenadine blood levels or P-gp and/or OATP activity (women stabilized on hormonal methods of birth control will be allowed to participate)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01526213

Locations
United States, North Carolina
North Carolina Clinical and Translational Research Center
Chapel Hill, North Carolina, United States, 27599
Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Principal Investigator: Mary F Paine, PhD UNC-Chapel Hill
  More Information

No publications provided

Responsible Party: Mary F. Paine, PhD, RPh, Assistant Professor, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT01526213     History of Changes
Other Study ID Numbers: IRB 09-0788
Study First Received: January 31, 2012
Results First Received: March 3, 2012
Last Updated: December 29, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Psoralens
Fexofenadine
Terfenadine
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Photosensitizing Agents
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Anti-Allergic Agents
Histamine H1 Antagonists, Non-Sedating
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014