Healthy VolunteersPhase 1NCT01731067
Cocktail Approach for Cytochrome P450 and P-glycoprotein Activity Assessment Using Dried Blood Spot
A Phase 1 study testing Cocktail probe drugs in people with Healthy Volunteers, run by Jules Desmeules at 1 site in Switzerland.
Trial summary
Phenotyping is an approach largely used for the evaluation of the activity of cytochromes and transporters in vivo. It consists of the administration of probe substances metabolised by a specific cytochrome or transported by P-glycoprotein (P-gp) for example, followed by the determination of a metabolic ratio or the… Read more about this study
- Who is it for?
- Ages 18 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Cocktail probe drugs
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteSwitzerland
- Study dates
- Nov 2012to Jan 2014
- Phase
- Phase 1
- 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
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy male volunteers aged from 18 to 60 years
- BMI between 18 and 25
- Understanding of French language and able to give a written inform consent.
Who cannot join
- Smoker
- Taking drugs which alter CYPs activity
- Renal or hepatic impairment
- Medical history of porphyria
- Medical history of chronic alcoholism or abuse of psychoactive drugs
- Liver transplantation
Show all 11Show fewer
- Sensitivity to any of the drugs used
- Wearing contact lenses (risk of coloration with rifampicin)
- ECG showing long QT interval (>0.46sec)
- Alteration of hepatic tests
- Presenting genetic polymorphism of poor CYP 2B6, 2C9, 2C19, 2D6 metabolisers
Trial locations and contacts
1 site in 1 country.
About this study
Phenotyping is an approach largely used for the evaluation of the activity of cytochromes and transporters in vivo. It consists of the administration of probe substances metabolised by a specific cytochrome or transported by P-glycoprotein (P-gp) for example, followed by the determination of a metabolic ratio or the evaluation of the plasmatic or urinary concentrations of the probe substances. The administration of a cocktail containing several probe substances allows the simultaneous evaluation of the activity of several cytochromes and P-gp in a single test.
The aim of this project is the validation of a phenotyping cocktail of low dose probe drugs for the assessment of cytochrome P450 and P-gp activities by simple capillary blood sampling and dried blood spot (DBS) analysis. The cocktail consists of caffeine, bupropion, flurbiprofen, omeprazole, dextromethorphan, midazolam and fexofenadine for the simultaneous phenotyping of CYP1A2, CYP2B6, CYP2C9, CAP2C19, CYP2D6, CYP3A4 and P-gp, respectively.
The modulation of the activity of cytochromes or P-gp will be evaluated by the administration of inhibitors (fluvoxamine, voriconazole, quinidine) or inducer (rifampicin) of the metabolic pathways or the P-gp mediated transport.
- Conditions
- Healthy Volunteers
- Being tested
- Cocktail probe drugs
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cocktail probe drugsDrug
Also called Oral intake of the cocktail probe drugs :, bupropion 25 mg, flurbiprofen 25 mg, omeprazole 5 mg
| Study group | Role | What they receive |
|---|---|---|
| CYP1A2, 2B6, 2C9, 2C19, 3A4 inhibitors | Active comparator | Oral intake of fluvoxamine (50 mg per day during 2 days) and voriconazole (400 mg) before oral intake of the cocktail probe drugs Receives: Drug: Cocktail probe drugs |
| CYP2D6 and P-gp inhibitor | Active comparator | Oral intake of quinidine (200 mg) before oral intake of the cocktail probe drugs Receives: Drug: Cocktail probe drugs |
| CYPs and P-gp inducer | Active comparator | Oral intake of rifampicin (600 mg per day during 7 days) before oral intake of the cocktail probe drugs Receives: Drug: Cocktail probe drugs |
| Probe cocktail alone | Experimental | Oral intake of the cocktail probe drugs :
* bupropion 25 mg
* flurbiprofen 25 mg
* omeprazole 5 mg
* dextromethorphan 5 mg
* midazolam 1 mg
* fexofenadine 25mg
* Caffeine (a cup of coffee) Receives: Drug: Cocktail probe drugs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Probe cocktail drugs plasma and capillary concentrations in presence/absence of CYP1A2,2B6, 2C9, 2C19, 2D6, 3A4 and P-gp inhibitor or inducer
Measured: 4 singles days spaced out with one week wash-out periods
Secondary outcomes (2)
correlation between plasma or urine and capillary concentrations for each probe cocktail drug
Measured: 4 singles days spaced out with one week wash-out periods
comparison. between genotype and phenotype for each enzyme
Measured: one day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2012 (estimated)
- Study startNov 2012
- Primary completionMay 2013
- Study completionJan 2014
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 Healthy VolunteersStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jules Desmeules
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jules Desmeules, University Hospital, Geneva
- Investigators
- Jules A Desmeules, Pr, Principal investigator, University Hospital, Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01731067
- Sponsor's protocol ID
- Coktail DBS
- Status last verified
- Sep 2014
- First submitted
- 14 Nov 2012
- Last updated
- 16 Sep 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Bosilkovska M, Samer CF, Deglon J, Rebsamen M, Staub C, Dayer P, Walder B, Desmeules JA, Daali Y. Geneva cocktail for cytochrome p450 and P-glycoprotein activity assessment using dried blood spots. Clin Pharmacol Ther. 2014 Sep;96(3):349-59. doi: 10.1038/clpt.2014.83. Epub 2014 Apr 10.
PubMed 24722393
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cocktail Approach for Cytochrome P450 and P-glycoprotein Activity Assessment Using Dried Blood Spot
- ClinicalTrials.gov ID
- NCT01731067
- Acronym / sponsor ID
- Coktail DBS
- Conditions
- Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Jules DesmeulesUniversity, hospital or other
- Study start
- Nov 2012
- Primary completion
- May 2013 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 21 Nov 2012 (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.
Phenotyping is an approach largely used for the evaluation of the activity of cytochromes and transporters in vivo. It consists of the administration of probe substances metabolised by a specific cytochrome or transported by P-glycoprotein (P-gp) for example, followed by the determination of a metabolic ratio or the evaluation of the plasmatic or urinary concentrations of the probe substances. The administration of a cocktail containing several probe substances allows the simultaneous evaluation of the activity of several cytochromes and P-gp in a single test.
The aim of this project is the validation of a phenotyping cocktail of low dose probe drugs for the assessment of cytochrome P450 and P-gp activities by simple capillary blood sampling and dried blood spot (DBS) analysis. The cocktail consists of caffeine, bupropion, flurbiprofen, omeprazole, dextromethorphan, midazolam and fexofenadine for the simultaneous phenotyping of CYP1A2, CYP2B6, CYP2C9, CAP2C19, CYP2D6, CYP3A4 and P-gp, respectively.
The modulation of the activity of cytochromes or P-gp will be evaluated by the administration of inhibitors (fluvoxamine, voriconazole, quinidine) or inducer (rifampicin) of the metabolic pathways or the P-gp mediated transport.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| CYP1A2, 2B6, 2C9, 2C19, 3A4 inhibitors | Active comparator | Drug: Cocktail probe drugsOral intake of fluvoxamine (50 mg per day during 2 days) and voriconazole (400 mg) before oral intake of the cocktail probe drugs |
| CYP2D6 and P-gp inhibitor | Active comparator | Drug: Cocktail probe drugsOral intake of quinidine (200 mg) before oral intake of the cocktail probe drugs |
| CYPs and P-gp inducer | Active comparator | Drug: Cocktail probe drugsOral intake of rifampicin (600 mg per day during 7 days) before oral intake of the cocktail probe drugs |
| Probe cocktail alone | Experimental | Drug: Cocktail probe drugsOral intake of the cocktail probe drugs : * bupropion 25 mg * flurbiprofen 25 mg * omeprazole 5 mg * dextromethorphan 5 mg * midazolam 1 mg * fexofenadine 25mg * Caffeine (a cup of coffee) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Healthy male volunteers aged from 18 to 60 years
- BMI between 18 and 25
- Understanding of French language and able to give a written inform consent.
Key exclusion criteria (11 listed)
- Smoker
- Taking drugs which alter CYPs activity
- Renal or hepatic impairment
- Medical history of porphyria
- Medical history of chronic alcoholism or abuse of psychoactive drugs
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 |
|---|---|---|
| Cocktail probe drugsAlso: Oral intake of the cocktail probe drugs :, bupropion 25 mg, flurbiprofen 25 mg, omeprazole 5 mg | Drug | CYP1A2, 2B6, 2C9, 2C19, 3A4 inhibitors, CYP2D6 and P-gp inhibitor, CYPs and P-gp inducer, Probe cocktail alone |
Primary outcome
Probe cocktail drugs plasma and capillary concentrations in presence/absence of CYP1A2,2B6, 2C9, 2C19, 2D6, 3A4 and P-gp inhibitor or inducer
Time frame: 4 singles days spaced out with one week wash-out periods
2 secondary outcomes
correlation between plasma or urine and capillary concentrations for each probe cocktail drug
Time frame: 4 singles days spaced out with one week wash-out periods
comparison. between genotype and phenotype for each enzyme
Time frame: one day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2014.
- Derived from this study: PubMed 24722393Bosilkovska M, Samer CF, Deglon J, Rebsamen M, Staub C, Dayer P, Walder B, Desmeules JA, Daali Y. Geneva cocktail for cytochrome p450 and P-glycoprotein activity assessment using dried blood spots. Clin Pharmacol Ther. 2014 Sep;96(3):349-59. doi: 10.1038/clpt.2014.83. Epub 2014 Apr 10.
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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.
Jules A Desmeules, Pr principal investigator
University Hospital, Geneva
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cocktail probe drugs in people with Healthy Volunteers, run by Jules Desmeules at 1 site in Switzerland.
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 11 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: finished, as of the sponsor's last update on 16 Sep 2014. 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 Switzerland. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Probe cocktail drugs plasma and capillary concentrations in presence/absence of CYP1A2,2B6, 2C9, 2C19, 2D6, 3A4 and P-gp inhibitor or inducer (time frame: 4 singles days spaced out with one week wash-out periods). 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 NCT01731067, 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 16 Sep 2014.