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

January 31, 2012
December 29, 2012
September 2009
April 2010   (final data collection date for primary outcome measure)
Primary Pharmacokinetic Measure: Area Under the Curve (AUC) [ Time Frame: 0-72 hours ] [ Designated as safety issue: No ]
Primary pharmacokinetic measures, AUC and Cmax [ Time Frame: 0-72 hours ] [ Designated as safety issue: No ]
Estimation of geometric mean ratios and 90% confidence intervals for the primary pharmacokinetic measures, AUC and Cmax.
Complete list of historical versions of study NCT01526213 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Do Furanocoumarins Mediate the Fexofenadine-grapefruit Juice Interaction?
Do Furanocoumarins Mediate the Fexofenadine-grapefruit Juice Interaction?

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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Food-drug Interaction
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 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.
    Intervention: Drug: Fexofenadine
  • 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.
    Intervention: Drug: Fexofenadine
  • 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.
    Intervention: Drug: Fexofenadine
  • 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.
    Intervention: Drug: Fexofenadine
  • 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.
    Intervention: Drug: Fexofenadine
  • 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.
    Intervention: Drug: Fexofenadine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
18
April 2011
April 2010   (final data collection date for primary outcome measure)

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)
Both
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01526213
IRB 09-0788
No
Mary F. Paine, PhD, RPh, University of North Carolina, Chapel Hill
University of North Carolina, Chapel Hill
Not Provided
Principal Investigator: Mary F Paine, PhD UNC-Chapel Hill
University of North Carolina, Chapel Hill
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP