Effects of Genotype on CYP2C9 Drug Interactions
2 other identifiers
observational
23
1 country
1
Brief Summary
This research study will help determine how a person's genetic makeup affects their responses to drugs, the ability of the body to break down drugs, and their potential to experience an interaction between drugs. We are investigating the drug interactions between an antifungal drug called fluconazole and the commonly used drugs tolbutamide, flurbiprofen, and ketoprofen. Tolbutamide is used for management of Type 2 diabetes. Both flurbiprofen and ketoprofen are non-steroidal anti-inflammatory drugs (NSAIDs) often used for arthritis or pain. We are interested in studying whether individuals with certain genetic profiles have different drug interactions than normal. This research is being done to see if certain genetic profiles require us to adjust medication doses differently than is needed for the general population. Genetic profiles of subjects are determined from their previous participation in the Pharmacogenetics Registry (Investigator Richard Brundage, University of Minnesota). The study hypothesis is: Fraction metabolized by CYP2C9 enzyme determines the extent of drug interactions in CYP2C9\*1/\*1 individuals but this factor (fraction metabolized) becomes less influential and drug interactions are attenuated in a gene-dose dependent manner in individuals with one or more defective alleles.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for all trials
Started Dec 2009
Longer than P75 for all trials
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
Study Start
First participant enrolled
December 1, 2009
CompletedFirst Submitted
Initial submission to the registry
January 29, 2010
CompletedFirst Posted
Study publicly available on registry
February 2, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
June 1, 2014
CompletedJuly 18, 2019
July 1, 2019
4.5 years
January 29, 2010
July 15, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Flurbiprofen Clearance
Measure of blood concentrations of Flurbiprofen 48 hours post Flurbiprofen dose
48 hours post Flurbiprofen dose
Ketoprofen Clearance
Measure of blood concentrations of Ketoprofen 48 hours post Ketoprofen dose
48 hours post Ketoprofen dose
Tolbutamide Clearance
Measure of blood concentrations of Tolbutamide 48 hours post Tolbutamide dose
48 hours post Tolbutamide dose
Study Arms (3)
CYP2C9*1/*1 Genotype
This genotype is considered the wild type genotype. Individuals with the CYP2C9\*1/\*1 genotype have two \*1 alleles and participated in the following interventions: Flurbiprofen Control - Flurbiprofen Only, Flurbiprofen Inhibition - Flurbiprofen \& Fluconazole, Ketoprofen Control - Ketoprofen Only, Ketoprofen Inhibition - Ketoprofen \& Fluconazole, Tolbutamide Control - Tolbutamide Only, and Tolbutamide Inhibition - Tolbutamide \& Fluconazole.
CYP2C9*1/*3 Genotype
Individuals with the CYP2C9\*1/\*3 genotype have one \*1 allele and one \*3 allele and participated in the following interventions: Flurbiprofen Control - Flurbiprofen Only, Flurbiprofen Inhibition - Flurbiprofen \& Fluconazole, Ketoprofen Control - Ketoprofen Only, Ketoprofen Inhibition - Ketoprofen \& Fluconazole, Tolbutamide Control - Tolbutamide Only, and Tolbutamide Inhibition - Tolbutamide \& Fluconazole.
CYP2C9*3/*3 Genotype
Individuals with the CYP2C9\*3/\*3 genotype have two \*3 alleles and participated in the following interventions: Flurbiprofen Control - Flurbiprofen Only, Flurbiprofen Inhibition - Flurbiprofen \& Fluconazole, Ketoprofen Control - Ketoprofen Only, Ketoprofen Inhibition - Ketoprofen \& Fluconazole, Tolbutamide Control - Tolbutamide Only, and Tolbutamide Inhibition - Tolbutamide \& Fluconazole.
Interventions
A single 50 mg flurbiprofen dose taken at the start of the study period. No other drugs administered during this study period.
A single 50 mg flurbiprofen dose taken at the start of the study period. 400 mg fluconazole taken every morning starting a week before the start of the study period and continuing throughout the study period.
A single 75 mg ketoprofen dose taken at the start of the study period. No other drugs administered during this study period.
A single 75 mg ketoprofen dose taken at the start of the study period. 400 mg fluconazole taken every morning starting a week before the start of the study period and continuing throughout the study period.
A single 500 mg tolbutamide dose taken at the start of the study period. No other drugs administered during this study period.
A single 500 mg tolbutamide dose taken at the start of the study period. 400 mg fluconazole taken every morning starting a week before the start of the study period and continuing throughout the study period.
Eligibility Criteria
Subjects are selected from a pharmacogenetics registry in which their drug metabolism genotype has been determined.
You may qualify if:
- Subjects will be 18-60 years old.
- Women of child-bearing age must be willing to use measures to avoid conception during the study period.
- Subjects must agree not to take any known substrates, inhibitors, inducers, or activators of CYP2C9.
You may not qualify if:
- Current cigarette smoker.
- Abnormal renal or liver function tests, physical exam, or recent history of hepatic, renal, gastrointestinal or neoplastic disease.
- Allergy to tolbutamide, flurbiprofen, ketoprofen, fluconazole or phenytoin and other chemically related drugs.
- Recent ingestion (\< 1 week) of any medication known to be metabolized by or alter activity of CYP2C9.
- A positive pregnancy test during the time of the pharmacokinetic study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Clinical and Translational Science Institute
Minneapolis, Minnesota, 55414, United States
Biospecimen
Plasma and urine samples are to be retained.
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Richard Brundage, PhD
University of Minnesota
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 29, 2010
First Posted
February 2, 2010
Study Start
December 1, 2009
Primary Completion
June 1, 2014
Study Completion
June 1, 2014
Last Updated
July 18, 2019
Record last verified: 2019-07