Cytochrome P450 Phenotype and Genotype MetricsNCT00981929
Development of Cocktail for Measuring the Activity of Important Cytochrome P450 Enzymes
A study testing Tramadol, Omeprazole, losartan, caffeine and Tramadol, omeprazole, losartan, caffeine in people with Cytochrome P450 Phenotype and Genotype Metrics, run by University of Southern Denmark at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Cytochrome P450 Phenotype and Genotype Metrics
- What is being tested?
- Tramadol, Omeprazole, losartan, caffeine and Tramadol, omeprazole, losartan, caffeine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 412 participants
- Where
- 1 siteDenmark
- Study dates
- Sep 2009to Jan 2011
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy volunteers,
- Written consent, AND
- Age 18-65 years old.
Who cannot join
- Daily medication,
- Alcohol abuse,
- Pregnancy, OR
- Breastfeeding.
Trial locations and contacts
1 site in 1 country.
Denmark1 site
University of Southern Denmark, Clinical Pharmacology
Odense, Fyn, D-5000
About this study
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).
Read more
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.
- Being tested
- Tramadol, Omeprazole, losartan, caffeine, Tramadol, omeprazole, losartan, caffeine
- Keywords
- CYP2D6, CYP2C9, CYP2C19, CYP1A2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TramadolDrug
50 mg single oral dose
Omeprazole, losartan, caffeineDrug
20 mg omeprazole 25 mg losartan 200 mg caffeine
Tramadol, omeprazole, losartan, caffeineDrug
50 mg tramadol 20 mg omeprazole 25 mg losartan 200 mg caffeine
| Study group | Role | What they receive |
|---|---|---|
| Tramadol | Active comparator | CYP2D6 metric Receives: Drug: Tramadol |
| Omeprazole, losartan, caffeine | Active comparator | CYP2C19, CYP2C9 and CYP1A2 metrics Receives: Drug: Omeprazole, losartan, caffeine |
| Tramadol, omeprazole, losartan and caffeine | Active comparator | CYP2D6, CYP2C19, CYP2C9 and CYP1A2 metrics Receives: Drug: Tramadol, omeprazole, losartan, caffeine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Metabolic ratios
Measured: January 2011
Secondary outcomes (1)
Genetic variants
Measured: January 2011
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2009 (estimated)
- Study startSep 2009
- Primary completionDec 2009 (estimated)
- Study completionJan 2011 (estimated)
Why it stopped: Unexpected non-serious adverse events
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cytochrome P450 Phenotype and Genotype MetricsStudies of the same condition, open and under way.
- More trials run by University of Southern DenmarkThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 412 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Southern Denmark
- Sponsor type
- University, hospital or other
- Collaborators
- Odense University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00981929
- Sponsor's protocol ID
- AKF-375
- Status last verified
- Jun 2010
- First submitted
- 21 Sep 2009
- Last updated
- 28 Jun 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 23917460
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development of Cocktail for Measuring the Activity of Important Cytochrome P450 Enzymes
- ClinicalTrials.gov ID
- NCT00981929
- Acronym / sponsor ID
- AKF-375
- Keywords
- CYP2D6, CYP2C9, CYP2C19, CYP1A2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unexpected non-serious adverse events
- Enrolment
- 412 participants (estimated)
- Lead sponsor
- University of Southern DenmarkUniversity, hospital or other
- Collaborators
- Odense University Hospital
- Study start
- Sep 2009
- Primary completion
- Dec 2009 (estimated)
- Study completion
- Jan 2011 (estimated)
- First posted
- 22 Sep 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Screening
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Tramadol | Active comparator | Drug: TramadolCYP2D6 metric |
| Omeprazole, losartan, caffeine | Active comparator | Drug: Omeprazole, losartan, caffeineCYP2C19, CYP2C9 and CYP1A2 metrics |
| Tramadol, omeprazole, losartan and caffeine | Active comparator | Drug: Tramadol, omeprazole, losartan, caffeineCYP2D6, CYP2C19, CYP2C9 and CYP1A2 metrics |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Healthy volunteers,
- Written consent, AND
- Age 18-65 years old.
Key exclusion criteria (4 listed)
- Daily medication,
- Alcohol abuse,
- Pregnancy, OR
- Breastfeeding.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tramadol50 mg single oral dose | Drug | Tramadol |
| Omeprazole, losartan, caffeine20 mg omeprazole 25 mg losartan 200 mg caffeine | Drug | Omeprazole, losartan, caffeine |
| Tramadol, omeprazole, losartan, caffeine50 mg tramadol 20 mg omeprazole 25 mg losartan 200 mg caffeine | Drug | Tramadol, omeprazole, losartan and caffeine |
Primary outcome
Metabolic ratios
Time frame: January 2011
1 secondary outcome
Genetic variants
Time frame: January 2011
Results and safety
The study was stopped early (reason given: Unexpected non-serious adverse events). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2010.
- Derived from this study: PubMed 23917460Pedersen 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tramadol, Omeprazole, losartan, caffeine and Tramadol, omeprazole, losartan, caffeine in people with Cytochrome P450 Phenotype and Genotype Metrics, run by University of Southern Denmark at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Jun 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Unexpected non-serious adverse events). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Metabolic ratios (time frame: January 2011). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00981929, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2010.