Development of Cocktail for Measuring the Activity of Imp... | NCT00981929

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

NCT00981929

Sponsor

University of Southern Denmark

Status

Terminated

Last Update Posted

Jun 28, 2010Estimated

Enrollment

412Estimated

Phase

Not Applicable

Conditions

Cytochrome P450 Phenotype and Genotype Metrics

Interventions

Tramadol
Omeprazole, losartan, caffeine
Tramadol, omeprazole, losartan, caffeine

Countries

Denmark

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

Status Module

Record Verification Date

Jun 2010

Overall Recruitment Status or Expanded Access Status

Terminated

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Unexpected non-serious adverse events

Expanded Access Info

Start Date

Sep 2009

Primary Completion Date

Dec 2009Estimated

Completion Date

Jan 2011Estimated

First Submitted Date

Sep 21, 2009

First Submission Date that Met QC Criteria

Sep 21, 2009

First Posted Date

Sep 22, 2009Estimated

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Jun 24, 2010

Last Update Posted Date

Jun 28, 2010Estimated

Name	Class
Odense University Hospital	OTHER

Oversight Module

Has Data Monitoring Committee (DMC)

Yes

Is FDA Regulated Drug

Not provided

Is FDA Regulated Device

Not provided

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

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

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Not Applicable

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

412Estimated

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Tramadol	Active Comparator	CYP2D6 metric	Drug: Tramadol
Omeprazole, losartan, caffeine	Active Comparator	CYP2C19, CYP2C9 and CYP1A2 metrics	Drug: Omeprazole, losartan, caffeine
Tramadol, omeprazole, losartan and caffeine	Active Comparator	CYP2D6, CYP2C19, CYP2C9 and CYP1A2 metrics	Drug: Tramadol, omeprazole, losartan, caffeine

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Tramadol	Drug	50 mg single oral dose	Tramadol
Omeprazole, losartan, caffeine

Measure	Description	Time Frame
Metabolic ratios		January 2011

Measure	Description	Time Frame
Genetic variants		January 2011

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

Daily medication,
Alcohol abuse,
Pregnancy, OR
Breastfeeding.

Accepts Healthy Volunteers

Yes

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

65 Years

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Contacts/Locations Module

Central Contacts

Not provided

Overall Officials

Not provided

Locations

Facility	Status	City	State	ZIP	Country	Contacts
University of Southern Denmark, Clinical Pharmacology		Odense	Fyn	D-5000	Denmark

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
23917460	Derived	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.

ID	Term
D014147	Tramadol
D009853	Omeprazole
D019808	Losartan
D002110	Caffeine

ID	Term
D003511	Cyclohexanols
D000441	Hexanols
D005233	Fatty Alcohols
D000438	Alcohols
D009930