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

NCT ID: NCT00981929

Last Updated: 2010-06-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

412 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-09-30

Study Completion Date

2011-01-31

Brief Summary

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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.

Detailed Description

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Conditions

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Cytochrome P450 Phenotype and Genotype Metrics

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

SCREENING

Blinding Strategy

NONE

Study Groups

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Tramadol

CYP2D6 metric

Group Type ACTIVE_COMPARATOR

Tramadol

Intervention Type DRUG

50 mg single oral dose

Omeprazole, losartan, caffeine

CYP2C19, CYP2C9 and CYP1A2 metrics

Group Type ACTIVE_COMPARATOR

Omeprazole, losartan, caffeine

Intervention Type DRUG

20 mg omeprazole 25 mg losartan 200 mg caffeine

Tramadol, omeprazole, losartan and caffeine

CYP2D6, CYP2C19, CYP2C9 and CYP1A2 metrics

Group Type ACTIVE_COMPARATOR

Tramadol, omeprazole, losartan, caffeine

Intervention Type DRUG

50 mg tramadol 20 mg omeprazole 25 mg losartan 200 mg caffeine

Interventions

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Tramadol

50 mg single oral dose

Intervention Type DRUG

Omeprazole, losartan, caffeine

20 mg omeprazole 25 mg losartan 200 mg caffeine

Intervention Type DRUG

Tramadol, omeprazole, losartan, caffeine

50 mg tramadol 20 mg omeprazole 25 mg losartan 200 mg caffeine

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* Daily medication,
* Alcohol abuse,
* Pregnancy, OR
* Breastfeeding.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Odense University Hospital

OTHER

Sponsor Role collaborator

University of Southern Denmark

OTHER

Sponsor Role lead

Responsible Party

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University of Southern Denmark

Locations

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University of Southern Denmark, Clinical Pharmacology

Odense, Fyn, Denmark

Site Status

Countries

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Denmark

References

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Pedersen RS, Damkier P, Christensen MM, Brosen K. A cytochrome P450 phenotyping cocktail causing unexpected adverse reactions in female volunteers. Eur J Clin Pharmacol. 2013 Dec;69(12):1997-9. doi: 10.1007/s00228-013-1561-1. Epub 2013 Aug 6.

Reference Type DERIVED
PMID: 23917460 (View on PubMed)

Other Identifiers

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AKF-375

Identifier Type: -

Identifier Source: org_study_id

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