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

Tracking Information
First Received Date ^ICMJE	September 21, 2009
Last Updated Date	June 24, 2010
Start Date ^ICMJE	September 2009
Estimated Primary Completion Date	December 2009 (final data collection date for primary outcome measure)
Current Primary Outcome Measures ^ICMJE (submitted: September 21, 2009)	Metabolic ratios [ Time Frame: January 2011 ] [ Designated as safety issue: No ]
Original Primary Outcome Measures ^ICMJE	Same as current
Change History	Complete list of historical versions of study NCT00981929 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ^ICMJE (submitted: September 21, 2009)	Genetic variants [ Time Frame: January 2011 ] [ Designated as safety issue: No ]
Original Secondary Outcome Measures ^ICMJE	Same as current
Current Other Outcome Measures ^ICMJE	Not Provided
Original Other Outcome Measures ^ICMJE	Not Provided

Descriptive Information
Brief Title ^ICMJE	Development of Cocktail for Measuring the Activity of Important Cytochrome P450 Enzymes
Official Title ^ICMJE	Development of Cocktail for Measuring the Activity of Important Cytochrome P450 Enzymes
Brief Summary	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	Not Provided
Study Type ^ICMJE	Interventional
Study Phase	Not Provided
Study Design ^ICMJE	Allocation: Non-Randomized Endpoint Classification: Pharmacokinetics Study Intervention Model: Crossover Assignment Masking: Open Label Primary Purpose: Screening
Condition ^ICMJE	Cytochrome P450 Phenotype and Genotype Metrics
Intervention ^ICMJE	Drug: Tramadol 50 mg single oral dose Drug: Omeprazole, losartan, caffeine 20 mg omeprazole 25 mg losartan 200 mg caffeine Drug: Tramadol, omeprazole, losartan, caffeine 50 mg tramadol 20 mg omeprazole 25 mg losartan 200 mg caffeine
Study Arm (s)	Active Comparator: Tramadol CYP2D6 metric Intervention: Drug: Tramadol Active Comparator: Omeprazole, losartan, caffeine CYP2C19, CYP2C9 and CYP1A2 metrics Intervention: Drug: Omeprazole, losartan, caffeine Active Comparator: Tramadol, omeprazole, losartan and caffeine CYP2D6, CYP2C19, CYP2C9 and CYP1A2 metrics Intervention: Drug: Tramadol, omeprazole, losartan, caffeine
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information
Recruitment Status ^ICMJE	Terminated
Estimated Enrollment ^ICMJE	412
Estimated Completion Date	January 2011
Estimated Primary Completion Date	December 2009 (final data collection date for primary outcome measure)
Eligibility Criteria ^ICMJE	Inclusion Criteria: Healthy volunteers, Written consent, AND Age 18-65 years old. Exclusion Criteria: Daily medication, Alcohol abuse, Pregnancy, OR Breastfeeding.
Gender	Both
Ages	18 Years to 65 Years
Accepts Healthy Volunteers	Yes
Contacts ^ICMJE	Contact information is only displayed when the study is recruiting subjects
Location Countries ^ICMJE	Denmark

Administrative Information
NCT Number ^ICMJE	NCT00981929
Other Study ID Numbers ^ICMJE	AKF-375
Has Data Monitoring Committee	Yes
Responsible Party	Kim Brosen / Professor, University of Southern Denmark
Study Sponsor ^ICMJE	University of Southern Denmark
Collaborators ^ICMJE	Odense University Hospital
Investigators ^ICMJE	Not Provided
Information Provided By	University of Southern Denmark
Verification Date	June 2010
^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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