PharmacokineticsPhase 4NCT02117869
The Effect of Low Furanocoumarin Grapefruit Hybrid Juice Consumption on Midazolam Pharmacokinetics
A Phase 4 study testing Low furanocoumarin hybrid grapefruit juice and Regular grapefruit juice in people with Pharmacokinetics, run by University of Florida at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetics
- What is being tested?
- Low furanocoumarin hybrid grapefruit juice and Regular grapefruit juice
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- May 2014to May 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 18-65 years of age
- non-smokers
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Clinical Research Center
Gainesville, Florida, 32611
About this study
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.
Read the detailed description
As a participant in this study the following will take place: A pre-study visit will be done which will include a physical exam, pregnancy test if applicable, and a review of your medical history. If you qualify you will then undergo three separate study visits as described below.
While participating in this study, participants will not eat grapefruit or other citrus fruits (oranges, lemons, for example) or drink non-study specific grapefruit juice or other citrus fruit juices, or citrus containing foods (orange marmalade, for example) for 1 week prior to each study visit. In addition, no herbal or other dietary supplements or over the counter medications should be taken for 48 hours before and during the study visits.
During each of the three study visits, separated by at least 2 weeks, one of two different grapefruit juice products (either the low furanocoumarin grapefruit hybrid or regular grapefruit) or water will be provided. The order in which these three drinks will be received will be random, like the toss of a coin. Also, 1 dose of midazolam (a drug normally used to make someone sleepy or relaxed before a medical test) will be given during each visit.
Each study visit will consist of three days, on Days 1 and 2 a drink of 200ml (about 7 ounces) of the assigned grapefruit juice or water will be given.
On Day 3 of each study visit, you will fast (abstain from having anything to eat or drink except water) from 12 a.m. the night before, and report to the clinic for the study day at 8am.
- Conditions
- Pharmacokinetics
- Being tested
- Low furanocoumarin hybrid grapefruit juice, Regular grapefruit juice, Water (control)
- Keywords
- Grapefruit juice
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low furanocoumarin hybrid grapefruit juiceOther
3 consecutive daily doses of 200ml low furanocoumarin grapefruit juice plus midazolam 5mg orally on the third day.
Regular grapefruit juiceOther
3 consecutive daily doses of 200ml regular grapefruit juice plus midazolam 5mg orally on the third day.
Water (control)Other
3 consecutive daily doses of 200ml water plus midazolam 5mg orally on the third day.
| Study group | Role | What they receive |
|---|---|---|
| Low furanocoumarin hybrid grapefruit juice | Experimental | 3 consecutive daily doses of 200ml low furanocoumarin hybrid grapefruit juice plus midazolam 5mg orally on the third day. Receives: Other: Low furanocoumarin hybrid grapefruit juice |
| Regular grapefruit juice | Active comparator | 3 consecutive daily doses of 200ml regular grapefruit juice plus midazolam 5mg orally on the third day. Receives: Other: Regular grapefruit juice |
| water (control) | Other | 3 consecutive daily doses of 200ml water plus midazolam 5mg orally on the third day. Receives: Other: Water (control) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Approximately 9 hours
Secondary outcomes (2)
Time to peak concentration
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.
Measured: Approximately 9 hours
Peak concentration
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.
Measured: Approximately 9 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2014 (estimated)
- Study startMay 2014
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PharmacokineticsStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rhonda M Copper-DeHoff, PharmD, MS, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02117869
- Sponsor's protocol ID
- IRB201300728
- Status last verified
- Jun 2015
- First submitted
- 16 Apr 2014
- Last updated
- 10 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Low Furanocoumarin Grapefruit Hybrid Juice Consumption on Midazolam Pharmacokinetics
- ClinicalTrials.gov ID
- NCT02117869
- Acronym / sponsor ID
- IRB201300728
- Conditions
- Pharmacokinetics
- Keywords
- Grapefruit juice
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- May 2014
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 21 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
As a participant in this study the following will take place: A pre-study visit will be done which will include a physical exam, pregnancy test if applicable, and a review of your medical history. If you qualify you will then undergo three separate study visits as described below.
While participating in this study, participants will not eat grapefruit or other citrus fruits (oranges, lemons, for example) or drink non-study specific grapefruit juice or other citrus fruit juices, or citrus containing foods (orange marmalade, for example) for 1 week prior to each study visit. In addition, no herbal or other dietary supplements or over the counter medications should be taken for 48 hours before and during the study visits.
During each of the three study visits, separated by at least 2 weeks, one of two different grapefruit juice products (either the low furanocoumarin grapefruit hybrid or regular grapefruit) or water will be provided. The order in which these three drinks will be received will be random, like the toss of a coin. Also, 1 dose of midazolam (a drug normally used to make someone sleepy or relaxed before a medical test) will be given during each visit.
Each study visit will consist of three days, on Days 1 and 2 a drink of 200ml (about 7 ounces) of the assigned grapefruit juice or water will be given.
On Day 3 of each study visit, you will fast (abstain from having anything to eat or drink except water) from 12 a.m. the night before, and report to the clinic for the study day at 8am.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low furanocoumarin hybrid grapefruit juice | Experimental | Other: Low furanocoumarin hybrid grapefruit juice3 consecutive daily doses of 200ml low furanocoumarin hybrid grapefruit juice plus midazolam 5mg orally on the third day. |
| Regular grapefruit juice | Active comparator | Other: Regular grapefruit juice3 consecutive daily doses of 200ml regular grapefruit juice plus midazolam 5mg orally on the third day. |
| water (control) | Other | Other: Water (control)3 consecutive daily doses of 200ml water plus midazolam 5mg orally on the third day. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 18-65 years of age
- non-smokers
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low furanocoumarin hybrid grapefruit juice3 consecutive daily doses of 200ml low furanocoumarin grapefruit juice plus midazolam 5mg orally on the third day. | Other | Low furanocoumarin hybrid grapefruit juice |
| Regular grapefruit juice3 consecutive daily doses of 200ml regular grapefruit juice plus midazolam 5mg orally on the third day. | Other | Regular grapefruit juice |
| Water (control)3 consecutive daily doses of 200ml water plus midazolam 5mg orally on the third day. | Other | water (control) |
Primary outcome
Area under the plasma concentration-time curves
Time frame: Approximately 9 hours
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.
2 secondary outcomes
Time to peak concentration
Time frame: Approximately 9 hours
Peak concentration
Time frame: Approximately 9 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rhonda M Copper-DeHoff, PharmD, MS principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Low furanocoumarin hybrid grapefruit juice and Regular grapefruit juice in people with Pharmacokinetics, run by University of Florida at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Area under the plasma concentration-time curves (time frame: Approximately 9 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2015.