Healthy VolunteersPhase 1Endo2C19NCT07014930
Identification of New Tools for Predicting Natural Metabolic Performance of the Liver
A Phase 1 study testing Inhibition session and Induction session in people with Healthy Volunteers, run by Caroline Samer at 1 site in Switzerland.
Trial summary
The objective of this clinical trial is to identify endogenous compounds (substances naturally present in the human body) that may serve as predictors of the activity of a key liver enzyme, CYP2C19. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Inhibition session and Induction session
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteSwitzerland
- Study dates
- 5 Dec 2024to Jan 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 men and women
- Age 18-65 years
- Body Mass Index (BMI) 18-27
- Understanding of French language and able to give a written inform consent
- CYP2C19 genotype: PMs, NMs, RMs or UMs
- At least one barrier method contraception during the whole study and 1 month after the end of the study (in addition of hormonal contraception if applicable)
Who cannot join
- CYP2C19 IMs
- Participation in any other interventional clinical study within 3 months prior to inclusion
- Pregnant or breastfeeding woman
- Any pathologies, use of drugs or food that may affect CYP activity (based on the 'drug interactions and cytochromes P450 table published by the Service of Clinical Pharmacology and Toxicology, HUG50 and on the investigator's knowledge)
- Medical history of liver transplantation
- Regular smokers of ≥ 10 cigarettes/day
Show all 14Show fewer
- Alcohol intake 2 days prior to session 1 and during fluvoxamine and rifampicin intake
- Alteration of hepatic tests (ASAT, ALAT, GGT, bilirubin more than 3x normal)
- Renal failure (serum urea, serum creatinine and eGFR outside the norms)
- Medical history of chronic alcoholism or abuse of psychoactive drugs
- Sensitivity to any of the drugs used
- Psychiatric disorders
- Beck Score ≥10 (question related to suicide >0)
- Contact lens wearers
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site, 1 recruiting
- Recruiting
The Geneva University Hospitals (HUG)
Geneva, 1211
Yahia Bennani, Master's degree, +41 78 733 14 23, yahia.bennani@hug.ch
About this study
Official title: Endobiotics for Phenotyping Cytochrome P450 Enzymes: Using Metabolomics to Identify Novel Endogenous CYP2C19 Activity Biomarkers in Healthy Volunteers
The objective of this clinical trial is to identify endogenous compounds (substances naturally present in the human body) that may serve as predictors of the activity of a key liver enzyme, CYP2C19. This enzyme plays a crucial role in the metabolism of several important drugs and exhibits significant interindividual variability in its activity, which can contribute to adverse drug reactions or reduced therapeutic efficacy.
The study will involve 40 healthy volunteers, divided into two groups: 10 poor metabolizers and 30 non-poor metabolizers. Each participant will undergo three sessions.
Read more
In the first session, 24-hour urine collection and plasma sampling will be conducted. Omeprazole will be administered orally, and the baseline blood OH-omeprazole/omeprazole ratio will be determined via capillary blood sampling.
The second session, identical in procedure to the first, will take place after 7 days of fluvoxamine administration (inhibition phase). The third session will also mirror the first but will follow 10 days of rifampicin administration (induction phase).
Endogenous compounds showing significant variation across sessions and between metabolizer groups will be evaluated as potential biomarkers for predicting CYP2C19 activity.
Read the detailed description
CYP2C19 is involved in the metabolism of approximately 6.8% of all marketed drugs. Its enzymatic activity varies significantly between individuals due to genetic polymorphisms, environmental factors, ethnicity, or disease states. While the administration of a CYP2C19 probe drug, such as omeprazole, is a reliable method for phenotyping this enzyme, it is relatively invasive and not suitable for certain vulnerable populations, such as pregnant women.
Identifying an endogenous compound metabolized by CYP2C19 could provide a non-invasive alternative to conventional phenotyping methods. This clinical study aims to identify such endogenous biomarkers by evaluating the effects of genetic variation, enzyme inhibition and induction on the metabolome of healthy volunteers.
To achieve this, untargeted metabolomic profiling using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) will be conducted on plasma, extracellular vesicles and urine samples.
This single-centre, open-label clinical trial will enroll 40 healthy participants (both men and women), aged 18 to 65 years. Participants will be assigned to one of two groups based on their CYP2C19 genotype: poor metabolizers (PMs) and normal, rapid, or ultrarapid metabolizers (NMs, RMs, UMs).
Each participant will undergo three study sessions:
Session 1: CYP2C19 phenotyping following a single 10 mg oral dose of omeprazole.
Session 2: Identical to Session 1, but following a 7-day pretreatment with fluvoxamine (CYP2C19 inhibitor, 50 mg once daily).
Session 3: Identical to Session 1, but following a 10-day pretreatment with rifampicin (CYP2C19 inducer, 600 mg once daily).
In all sessions, urine will be collected for 24 hours and venous blood samples will be taken prior to omeprazole administration for metabolomics analysis. Capillary blood will also be sampled after omeprazole intake to assess the CYP2C19 phenotype.
- Conditions
- Healthy Volunteers
- Being tested
- Control session, Inhibition session, Induction session
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Control sessionDrug
Plasma and urine sampling as well as the determination of the blood OH-omeprazole/omeprazole ratio at baseline by capillary blood sampling.
Inhibition sessionDrug
Plasma and urine sampling as well as the determination of the blood OH-omeprazole/omeprazole ratio at baseline by capillary blood sampling, with prior administration of 50 mg of fluvoxamine for 7 consecutive days (CYP2C19 inhibitor).
Induction sessionDrug
Plasma and urine sampling as well as the determination of the blood OH-omeprazole/omeprazole ratio at baseline by capillary blood sampling, with prior administration of 600 mg of rifampicin for 10 consecutive days (CYP2C19 inducer).
| Study group | Role | What they receive |
|---|---|---|
| CYP2C19 Poor Metabolizers (PMs) | Experimental | Carriers of two non-functional alleles of CYP2C19 Receives: Drug: Control session; Drug: Inhibition session; Drug: Induction session |
| CYP2C19 Normal, Rapid or Ultrarapid Metabolizers (NMs-RMs-UMs) | Experimental | Carriers of two normally functional alleles (NMs), one normally functional allele and one increased-functional allele (RMs) or two increased-functional alleles of CYP2C19 (UMs). Receives: Drug: Control session; Drug: Inhibition session; Drug: Induction session |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fold-change in the intensities of features determined by mass spectrometry according to genotype (PMs versus NMs-RMs-UMs) and according to sessions.
Metabolic features showing a fold-change ≥ 1.5 or ≤ 0.6737 will be qualified as CYP2C19 endogenous biomarkers. Chromatographic signals will be detected in healthy volunteers' urine, plasma and liver-derived extracellular vesicles by liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) at each session for each volunteer.
Measured: Samples collected at Session 1 (Day 1), Session 2 (Day 11 ± 4), and Session 3 (Day 27 ± 4); data analysis completed within 90 days after the final session of the last participant.
Secondary outcomes (2)
Correlation of significant ions measured in metabolomics with OH-OPZ/OPZ blood ratio.
Measured: Within 90 days after the last study session of the last participant.
Predictive performance metrics of a multivariate linear regression model for CYP2C19 phenotype.
Measured: Within 90 days after the last study session of the last participant.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2025
- Study start5 Dec 2024
- Primary completionNov 2025 (estimated)
- Study completionJan 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Caroline Samer
- Sponsor type
- University, hospital or other
- Collaborators
- Fonds national Suisse
- Responsible party
- Sponsor-investigator, Caroline Samer, University Hospital, Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07014930
- Sponsor's protocol ID
- 2023-01956
- Other IDs
- 2023
- Acronym
- Endo2C19
- Status last verified
- Jun 2025
- First submitted
- 19 May 2025
- Last updated
- 11 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endobiotics for Phenotyping Cytochrome P450 Enzymes: Using Metabolomics to Identify Novel Endogenous CYP2C19 Activity Biomarkers in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT07014930
- Acronym / sponsor ID
- Endo2C19 / 2023-01956
- Conditions
- Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Caroline SamerUniversity, hospital or other
- Collaborators
- Fonds national Suisse
- Study start
- 5 Dec 2024 (actual)
- Primary completion
- Nov 2025 (estimated)
- Study completion
- Jan 2026 (estimated)
- First posted
- 11 Jun 2025 (actual)
- 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 objective of this clinical trial is to identify endogenous compounds (substances naturally present in the human body) that may serve as predictors of the activity of a key liver enzyme, CYP2C19. This enzyme plays a crucial role in the metabolism of several important drugs and exhibits significant interindividual variability in its activity, which can contribute to adverse drug reactions or reduced therapeutic efficacy.
The study will involve 40 healthy volunteers, divided into two groups: 10 poor metabolizers and 30 non-poor metabolizers. Each participant will undergo three sessions.
In the first session, 24-hour urine collection and plasma sampling will be conducted. Omeprazole will be administered orally, and the baseline blood OH-omeprazole/omeprazole ratio will be determined via capillary blood sampling.
The second session, identical in procedure to the first, will take place after 7 days of fluvoxamine administration (inhibition phase). The third session will also mirror the first but will follow 10 days of rifampicin administration (induction phase).
Endogenous compounds showing significant variation across sessions and between metabolizer groups will be evaluated as potential biomarkers for predicting CYP2C19 activity.
Detailed description
CYP2C19 is involved in the metabolism of approximately 6.8% of all marketed drugs. Its enzymatic activity varies significantly between individuals due to genetic polymorphisms, environmental factors, ethnicity, or disease states. While the administration of a CYP2C19 probe drug, such as omeprazole, is a reliable method for phenotyping this enzyme, it is relatively invasive and not suitable for certain vulnerable populations, such as pregnant women.
Identifying an endogenous compound metabolized by CYP2C19 could provide a non-invasive alternative to conventional phenotyping methods. This clinical study aims to identify such endogenous biomarkers by evaluating the effects of genetic variation, enzyme inhibition and induction on the metabolome of healthy volunteers.
To achieve this, untargeted metabolomic profiling using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS) will be conducted on plasma, extracellular vesicles and urine samples.
This single-centre, open-label clinical trial will enroll 40 healthy participants (both men and women), aged 18 to 65 years. Participants will be assigned to one of two groups based on their CYP2C19 genotype: poor metabolizers (PMs) and normal, rapid, or ultrarapid metabolizers (NMs, RMs, UMs).
Each participant will undergo three study sessions:
Session 1: CYP2C19 phenotyping following a single 10 mg oral dose of omeprazole.
Session 2: Identical to Session 1, but following a 7-day pretreatment with fluvoxamine (CYP2C19 inhibitor, 50 mg once daily).
Session 3: Identical to Session 1, but following a 10-day pretreatment with rifampicin (CYP2C19 inducer, 600 mg once daily).
In all sessions, urine will be collected for 24 hours and venous blood samples will be taken prior to omeprazole administration for metabolomics analysis. Capillary blood will also be sampled after omeprazole intake to assess the CYP2C19 phenotype.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CYP2C19 Poor Metabolizers (PMs) | Experimental | Drug: Control session, Drug: Inhibition session, Drug: Induction sessionCarriers of two non-functional alleles of CYP2C19 |
| CYP2C19 Normal, Rapid or Ultrarapid Metabolizers (NMs-RMs-UMs) | Experimental | Drug: Control session, Drug: Inhibition session, Drug: Induction sessionCarriers of two normally functional alleles (NMs), one normally functional allele and one increased-functional allele (RMs) or two increased-functional alleles of CYP2C19 (UMs). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Healthy men and women
- Age 18-65 years
- Body Mass Index (BMI) 18-27
- Understanding of French language and able to give a written inform consent
- CYP2C19 genotype: PMs, NMs, RMs or UMs
Key exclusion criteria (14 listed)
- CYP2C19 IMs
- Participation in any other interventional clinical study within 3 months prior to inclusion
- Pregnant or breastfeeding woman
- Any pathologies, use of drugs or food that may affect CYP activity (based on the 'drug interactions and cytochromes P450 table published by the Service of Clinical Pharmacology and Toxicology, HUG50 and on the investigator's knowledge)
- Medical history of liver transplantation
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 |
|---|---|---|
| Control sessionPlasma and urine sampling as well as the determination of the blood OH-omeprazole/omeprazole ratio at baseline by capillary blood sampling. | Drug | CYP2C19 Normal, Rapid or Ultrarapid Metabolizers (NMs-RMs-UMs), CYP2C19 Poor Metabolizers (PMs) |
| Inhibition sessionPlasma and urine sampling as well as the determination of the blood OH-omeprazole/omeprazole ratio at baseline by capillary blood sampling, with prior administration of 50 mg of fluvoxamine for 7 consecutive days (CYP2C19 inhibitor). | Drug | CYP2C19 Normal, Rapid or Ultrarapid Metabolizers (NMs-RMs-UMs), CYP2C19 Poor Metabolizers (PMs) |
| Induction sessionPlasma and urine sampling as well as the determination of the blood OH-omeprazole/omeprazole ratio at baseline by capillary blood sampling, with prior administration of 600 mg of rifampicin for 10 consecutive days (CYP2C19 inducer). | Drug | CYP2C19 Normal, Rapid or Ultrarapid Metabolizers (NMs-RMs-UMs), CYP2C19 Poor Metabolizers (PMs) |
Primary outcome
Fold-change in the intensities of features determined by mass spectrometry according to genotype (PMs versus NMs-RMs-UMs) and according to sessions.
Time frame: Samples collected at Session 1 (Day 1), Session 2 (Day 11 ± 4), and Session 3 (Day 27 ± 4); data analysis completed within 90 days after the final session of the last participant.
Metabolic features showing a fold-change ≥ 1.5 or ≤ 0.6737 will be qualified as CYP2C19 endogenous biomarkers. Chromatographic signals will be detected in healthy volunteers' urine, plasma and liver-derived extracellular vesicles by liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) at each session for each volunteer.
2 secondary outcomes
Correlation of significant ions measured in metabolomics with OH-OPZ/OPZ blood ratio.
Time frame: Within 90 days after the last study session of the last participant.
Predictive performance metrics of a multivariate linear regression model for CYP2C19 phenotype.
Time frame: Within 90 days after the last study session of the last participant.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2025.
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Screening Protocol
Pain
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.
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 Inhibition session and Induction session in people with Healthy Volunteers, run by Caroline Samer 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 6 inclusion and 14 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: looking for participants now, as of the sponsor's last update on 11 Jun 2025. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yahia Bennani, Master's degree (+41 78 733 14 23, yahia.bennani@hug.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fold-change in the intensities of features determined by mass spectrometry according to genotype (PMs versus NMs-RMs-UMs) and according to sessions. (time frame: Samples collected at Session 1 (Day 1), Session 2 (Day 11 ± 4), and Session 3 (Day 27 ± 4); data analysis completed within 90 days after the final session of the last participant.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Jun 2025.