The Effect of Low Furanocoumarin Grapefruit Hybrid Juice Consumption on Midazolam Pharmacokinetics
1 other identifier
interventional
12
1 country
1
Brief Summary
Grapefruit (GF) contains furanocoumarin (FC) which is known to irreversibly inhibit the activity of cytochrome P450-3A (CYP3A) enzymes in the human gastrointestinal tract (PAINE 2005). Because CYP3A enzymes are integral in the metabolism of some drugs, co-ingesting GF or GF Juice (GFJ), which inhibits CYP3A, along with drugs reliant on CYP3A for metabolism can significantly alter the drugs kinetic properties and result in elevated plasma drug concentrations which may be toxic. The Citrus Research and Education Center at the University of Florida has developed a new GF hybrid (GFH) which contains low FC content and which may not inhibit CYP3A enzyme activity, and therefore may be safe to co-ingest with drugs that require CYP3A activity for metabolism. The investigators hypothesize that low FC GFHJ will not inhibit CYP3A to the degree that regular GFJ does, and will not significantly affect midazolam kinetics compared with regular GFJ. Midazolam is an FDA approved probe drug for CYP3A activity and has been used previously to establish an interaction between GFJ and midazolam. This study will evaluate the concomitant administration of midazolam and low FC GFHJ, regular GFJ, or water to evaluate the significance of this interaction.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_4
Started May 2014
Shorter than P25 for phase_4
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 16, 2014
CompletedFirst Posted
Study publicly available on registry
April 21, 2014
CompletedStudy Start
First participant enrolled
May 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2015
CompletedJune 10, 2015
June 1, 2015
1 year
April 16, 2014
June 8, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Area under the plasma concentration-time curves
For pharmacokinetic analysis, venous blood samples from an intravenous catheter in the arm will be collected prior to (0 hr, predose), and at 0.5, 1, 2, 3, 4, 6, and 9 hours after midazolam administration.
Approximately 9 hours
Secondary Outcomes (2)
Time to peak concentration
Approximately 9 hours
Peak concentration
Approximately 9 hours
Study Arms (3)
Low furanocoumarin hybrid grapefruit juice
EXPERIMENTAL3 consecutive daily doses of 200ml low furanocoumarin hybrid grapefruit juice plus midazolam 5mg orally on the third day.
Regular grapefruit juice
ACTIVE COMPARATOR3 consecutive daily doses of 200ml regular grapefruit juice plus midazolam 5mg orally on the third day.
water (control)
OTHER3 consecutive daily doses of 200ml water plus midazolam 5mg orally on the third day.
Interventions
3 consecutive daily doses of 200ml low furanocoumarin grapefruit juice plus midazolam 5mg orally on the third day.
3 consecutive daily doses of 200ml regular grapefruit juice plus midazolam 5mg orally on the third day.
3 consecutive daily doses of 200ml water plus midazolam 5mg orally on the third day.
Eligibility Criteria
You may qualify if:
- years of age
- non-smokers
You may not qualify if:
- Inability to abstain from alcoholic beverages (24 hours),
- Inability to abstain herbal containing supplements/teas/beverages, and
- Inability to abstain from over-the-counter medications (48 hours) prior to the study visits
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Clinical Research Center
Gainesville, Florida, 32611, United States
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rhonda M Copper-DeHoff, PharmD, MS
University of Florida
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 16, 2014
First Posted
April 21, 2014
Study Start
May 1, 2014
Primary Completion
May 1, 2015
Study Completion
May 1, 2015
Last Updated
June 10, 2015
Record last verified: 2015-06