Development of Cocktail for Measuring the Activity of Important Cytochrome P450 Enzymes

June 24, 2010 updated by: University of Southern Denmark

The Cytochrome P450 enzymes are responsible for the metabolism of a wide range of drugs and other xenobiotics. Genetic variants of the encoding P450 genes have shown to influence the rate of metabolism of many clinically used drugs.

The drugs tramadol, omeprazole, losartan, quinidine and caffeine reflect the activity of CYP2D6 (tramadol), CYP2C19 (omeprazole), CYP2C9 (losartan), CYP1A2 (caffeine) and CYP3A4/5 (quinidine).

The aim of the study is to investigate if the cocktail of tramadol, omeprazole, losartan and caffeine can be used to simultaneously determine the activity of CYP2D6, CYP2C19, CYP2C9 and CYP1A2. Furthermore, will the natural occurring 4-beta-hydroxy-cholesterol in the blood be measured as a metric for CYP3A4/5.

The study is divided in two. First part will include 12 healthy volunteers and consists of three arms separated by at least one week. In the first arm 50 mg of tramadol will be ingested and urine will be collected for 8 hours. In the second arm 20 mg omeprazole, 25 mg losartan and 200 mg caffeine will be ingested followed by 8 hours urine collection and a blood sample 4 hours after administration of the drugs. In the last arm 50 mg of tramadol, 20 mg omeprazole, 25 mg losartan and 200 mg caffeine will be ingested followed by 8 hours urine collection and a blood sample 4 hours after administration of the drugs.

Metabolic ratios will be calculated based on urine and plasma concentrations of the drugs and the relevant metabolites. Relevant genetic variants of the cytochrome P450 encoding genes will be determined.

If the metabolic ratios of the drugs are not significantly different between the arms, Second part of the study will be conducted.

This part is identical with the last arm and will include a maximum of 400 healthy volunteers: 50 mg of tramadol, 20 mg omeprazole, 25 mg losartan and 200 mg caffeine will be ingested followed by 8 hours urine collection and a blood sample 4 hours after administration of the drugs.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

412

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Fyn
      • Odense, Fyn, Denmark, D-5000
        • University of Southern Denmark, Clinical Pharmacology

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Healthy volunteers,
  • Written consent, AND
  • Age 18-65 years old.

Exclusion Criteria:

  • Daily medication,
  • Alcohol abuse,
  • Pregnancy, OR
  • Breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: SCREENING
  • Allocation: NON_RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Tramadol
CYP2D6 metric
Drug: Tramadol
50 mg single oral dose
ACTIVE_COMPARATOR: Omeprazole, losartan, caffeine
CYP2C19, CYP2C9 and CYP1A2 metrics
Drug: Omeprazole, losartan, caffeine
20 mg omeprazole 25 mg losartan 200 mg caffeine
ACTIVE_COMPARATOR: Tramadol, omeprazole, losartan and caffeine
CYP2D6, CYP2C19, CYP2C9 and CYP1A2 metrics
Drug: Tramadol, omeprazole, losartan, caffeine
50 mg tramadol 20 mg omeprazole 25 mg losartan 200 mg caffeine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Metabolic ratios
Time Frame: January 2011
January 2011

Secondary Outcome Measures

Outcome Measure
Time Frame
Genetic variants
Time Frame: January 2011
January 2011

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Southern Denmark

Collaborators

Odense University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2009

Primary Completion (ANTICIPATED)

December 1, 2009

Study Completion (ANTICIPATED)

January 1, 2011

Study Registration Dates

First Submitted

September 21, 2009

First Submitted That Met QC Criteria

September 21, 2009

First Posted (ESTIMATE)

September 22, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

June 28, 2010

Last Update Submitted That Met QC Criteria

June 24, 2010

Last Verified

June 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AKF-375

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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