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

This study has been terminated.

(Unexpected non-serious adverse events)

Sponsor:

Collaborator:

Odense University Hospital

Information provided by:

University of Southern Denmark

ClinicalTrials.gov Identifier:

NCT00981929

First received: September 21, 2009

Last updated: June 24, 2010

Last verified: June 2010

History of Changes

Purpose

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.

Condition	Intervention
Cytochrome P450 Phenotype and Genotype Metrics	Drug: Tramadol Drug: Omeprazole, losartan, caffeine Drug: Tramadol, omeprazole, losartan, caffeine

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Screening
Official Title:	Development of Cocktail for Measuring the Activity of Important Cytochrome P450 Enzymes

Resource links provided by NLM:

MedlinePlus related topics: Caffeine

Drug Information available for: Tramadol Omeprazole Omeprazole magnesium Losartan Esomeprazole Losartan potassium Esomeprazole Sodium Esomeprazole magnesium

U.S. FDA Resources

Further study details as provided by University of Southern Denmark:

Primary Outcome Measures:

Metabolic ratios [ Time Frame: January 2011 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Genetic variants [ Time Frame: January 2011 ] [ Designated as safety issue: No ]

Estimated Enrollment:	412
Study Start Date:	September 2009
Estimated Study Completion Date:	January 2011
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

Daily medication,
Alcohol abuse,
Pregnancy, OR
Breastfeeding.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00981929

Locations

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

Sponsors and Collaborators

University of Southern Denmark

Odense University Hospital

More Information

No publications provided

Responsible Party:	Kim Brosen / Professor, University of Southern Denmark
ClinicalTrials.gov Identifier:	NCT00981929 History of Changes
Other Study ID Numbers:	AKF-375
Study First Received:	September 21, 2009
Last Updated:	June 24, 2010
Health Authority:	Denmark: Danish Medicines Agency

Keywords provided by University of Southern Denmark:

CYP2D6
CYP2C9
CYP2C19
CYP1A2

Additional relevant MeSH terms:

Caffeine
Tramadol
Omeprazole
Losartan
Central Nervous System Stimulants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents

Neurotransmitter Agents
Anti-Ulcer Agents
Gastrointestinal Agents
Narcotics
Central Nervous System Depressants
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Analgesics, Opioid
Anti-Arrhythmia Agents
Cardiovascular Agents
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on May 16, 2013

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