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
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 by University of Southern Denmark

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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
Losartan
Omeprazole
Tramadol
Analgesics
Analgesics, Opioid
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists
Anti-Arrhythmia Agents
Anti-Ulcer Agents
Antihypertensive Agents
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Central Nervous System Stimulants
Enzyme Inhibitors
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Narcotics
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Phosphodiesterase Inhibitors
Physiological Effects of Drugs
Proton Pump Inhibitors
Purinergic Agents
Purinergic Antagonists
Purinergic P1 Receptor Antagonists
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014