HealthyPhase 1Switch19NCT05264142
Risk of CYP2C19 Phenoconversion in Healthy Volunteers With Rapid, Normal, and Intermediate Predicted Metabolizers' Status
A Phase 1 study testing Voriconazole 200mg, FluvoxaMINE 50 Mg Oral Tablet and Omeprazole 10 MG Oral Tablet in people with Healthy, run by University Hospital, Geneva at 1 site in Switzerland.
Trial summary
CYP2C19 is responsible for the metabolism of approximately 10% of drugs currently on the market, including several proton pump inhibitors, clopidogrel, benzodiazepines and some tricyclic antidepressants, including amitriptyline. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Voriconazole 200mg, FluvoxaMINE 50 Mg Oral Tablet and Omeprazole 10 MG Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Apr 2022to 31 Aug 2023
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy men and women ≥ 18 years old
- Understanding of French language and able to give a written consent
- Reliable contraception during the whole study, including a barrier method
- CYP2C19 genotype associated to the RM (*1/*17) , NM(*1/*1) AND IM(*1/*2-*2/*17) activity groups
Who cannot join
- 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 Pharmacoloy and Toxicology, HUG and on the investigator's knowledge)
- History of liver transplantation
- Alcohol intake during fluvoxamine intake
- Psychotropic substances use during fluvoxamine intake
Show all 13Show fewer
- Alteration of hepatic tests (ASAT, ALAT, GGT, BILI) more than 3x normal
- Glomerular filtration rate (GFR) < 60 ml/min/1.73 m2
- Medical history of chronic alcoholism or abuse of psychoactive drugs
- Regular use of psychotropic substances
- Sensitivity to any of the drugs used
- Psychiatric disorders
- Beck Score ≥ 10 (question related to suicide >0)
Trial locations and contacts
1 site in 1 country.
Switzerland1 site, 1 recruiting
- Recruiting
Geneva University Hospitals, HUG
Geneva
Caroline Samer, Dr, caroline.samer@hcuge.ch
Kenza Abouir, kenza.abouir@hcuge.ch
About this study
Official title: Impact of Genetic Polymorphism on Drug Interactions Involving CYP2C19: Risk of Phenoconversion in Healthy CYP2C19 Fast, Normal and Intermediate Metabolizers Status
CYP2C19 is responsible for the metabolism of approximately 10% of drugs currently on the market, including several proton pump inhibitors, clopidogrel, benzodiazepines and some tricyclic antidepressants, including amitriptyline. It is a cytochrome whose activity is characterized by a great variability in the general population. This variability can be explained, in part, by genetic and environmental factors The classification of phenotypes associated with CYP2C19 has evolved over time. Today, five distinct phenotypes are used to characterize this variability: the slow metabolizer (SM) phenotype, the intermediate metabolizer (IM) phenotype, the normal metabolizer (NM) phenotype, the fast metabolizer (RM) phenotype and finally the ultra-fast metabolizer (UM) phenotype. (UM) phenotype.
Although directly measurable with test substances, CYP2C19 phenotypes are often assigned on the basis of genotype. They may be impacted by intrinsic (e.g., comorbidities) or extrinsic (e.g., co-medications) factors. Phenoconversion or phenotypic change is the phenomenon by which an individual switches from one phenotype to another due to an environmental influence such as a drug interaction. However, genotype is likely to influence the degree of response to a drug interaction. Vulnerability to phenoconversion therefore differs according to the genotype of the individual.
The purpose of our study is to determine whether individuals genetically MR, NM and IM have the same vulnerability to phenoconversion. Thus, the magnitude of the response to CYP2C19 inhibition will be studied in these 3 groups of individuals (NM:*1/*1, RM:*1/*17 and IM:*1/*2-*2/*17). Inhibition will be studied in two steps, using a strong (fluvoxamine) and a weak (voriconazole) inhibitor of CYP2C19.
Read the detailed description
Phase 1, open-label, parallel study in healthy volunteers selected according to their genotypic belonging to one of the three study groups.
Volunteers are included in the study and go through a buccal swab for genotyping, allowing their allocation into 3 groups according to their CYP2C19 genotype (RM: *1/*17 - NM: *1/*1 - IM: *1/*2 and *2/*17).
Following this step, volunteers have an inclusion session to determine if they meet the inclusion and non-exclusion criteria for the study.
The included volunteers will participate in three study sessions will take place.
Session 1 (control session): administration of 10mg of omeprazole for CYP2C19 phenotyping Session 2: same as session 1 with a prior intake of voriconazole 400 mg (weak inhibitor of CYP2C19 2 hours before omeprazole intake) Session 3: same as session 1 with a prior intake of fluvoxamine (strong CYP2C19 inhibitor, 12 h before and 2 h before taking the omeprazole)
At each session, dried blood spot (DBS) samples will be collected before the intake of the omeprazole (T0) and then at 2, 3, 6 and 8 hours after taking the capsule.
A wash-out period of minimum 3 days will be observed between session 1 and 2 and of minimum 1 week will be observed between sessions 2 and 3.
- Conditions
- Healthy
- Being tested
- Voriconazole 200mg, FluvoxaMINE 50 Mg Oral Tablet, Omeprazole 10 MG Oral Tablet
- Keywords
- Phenoconversion, Pharmakinetics, Genotype, Cytochrome 2C19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Voriconazole 200mgDrug
Also called J02AC03
Voriconazole is a weak CYP2C19 inhibitor. It is used in study session 2 to study the impact of a weak inhibitor on the phenotype switch among the different genotypes included in the study.
FluvoxaMINE 50 Mg Oral TabletDrug
Also called N06AB08
Fluvoxamine is a strong CYP2C19 inhibitor. It is used in study session 3 to study the impact of a strong inhibitor on the phenotype switch among the different genotypes included in the study.
Omeprazole 10 MG Oral TabletDrug
Also called A02BC01
Omeprazole is a CYP2C19 probe substrate. It is used in the study as a tool for CYP2C19 phenotyping at each of the sessions.
| Study group | Role | What they receive |
|---|---|---|
| CYP2C19 Rapid Metabolizers (RM) | Experimental | CYP2C19 rapid metabolizers (RM) are characterized by one normal function allele and one increased function allele Receives: Drug: Voriconazole 200mg; Drug: FluvoxaMINE 50 Mg Oral Tablet; Drug: Omeprazole 10 MG Oral Tablet |
| CYP2C19 Normal metabolizers (NM) | Experimental | CYP2C19 normal metabolizers (NMs) harboring two normal function alleles defined by the lack of any characterized polymorphisms. Receives: Drug: Voriconazole 200mg; Drug: FluvoxaMINE 50 Mg Oral Tablet; Drug: Omeprazole 10 MG Oral Tablet |
| CYP2C19 Intermediate metabolizers (IM) | Experimental | CYP2C19 intermediate metabolizers (IMs) are characterized by the presence of one normal function allele and one no function allele or one no function allele and one increased function allele. Receives: Drug: Voriconazole 200mg; Drug: FluvoxaMINE 50 Mg Oral Tablet; Drug: Omeprazole 10 MG Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phenoconversion rate
The proportion of volunteers in each group who acquire a phenotype switch such as from NM to PM after pre-treatment by voriconazole and fluvoxamine (weak and strong inhibitors, respectively)
Measured: 2 months
Secondary outcomes (4)
AUC assessment
Test drugs and their metabolite AUC measurement in whole capillary blood as well as metabolite /probe AUC ratio and single points metabolic ratios.
Measured: 1 year
CL assessment
Test drugs and their metabolite Cl measurement in whole capillary blood
Measured: 1 year
Cmax assessment
Test drugs and their metabolite Cmax measurement in whole capillary blood
Measured: 1 year
Tmax assessment
Test drugs and their metabolite Tmax measurement in whole capillary blood
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2022
- Study start1 Apr 2022
- Primary completion31 Mar 2023 (estimated)
- Study completion31 Aug 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by University Hospital, GenevaThe 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 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The study will include 3 distinct CYP2C19 genotype groups that will constitute the 3 arms of the study. For each volunteer, the study will consist of 3 sessions. Same drugs will be administered to the 3 arms of the study.
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Geneva
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Caroline Samer, University Hospital, Geneva
- Investigators
- Caroline Samer, Prof, Principal investigator, Division of Clinical Pharmacology and Toxicology, Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05264142
- Sponsor's protocol ID
- 2022-XXXX
- Acronym
- Switch19
- Status last verified
- Oct 2022
- First submitted
- 11 Feb 2022
- Last updated
- 3 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Genetic Polymorphism on Drug Interactions Involving CYP2C19: Risk of Phenoconversion in Healthy CYP2C19 Fast, Normal and Intermediate Metabolizers Status
- ClinicalTrials.gov ID
- NCT05264142
- Acronym / sponsor ID
- Switch19 / 2022-XXXX
- Conditions
- Healthy
- Keywords
- Phenoconversion, Pharmakinetics, Genotype, Cytochrome 2C19
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- University Hospital, GenevaUniversity, hospital or other
- Study start
- 1 Apr 2022 (actual)
- Primary completion
- 31 Mar 2023 (estimated)
- Study completion
- 31 Aug 2023 (estimated)
- First posted
- 3 Mar 2022 (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.
CYP2C19 is responsible for the metabolism of approximately 10% of drugs currently on the market, including several proton pump inhibitors, clopidogrel, benzodiazepines and some tricyclic antidepressants, including amitriptyline. It is a cytochrome whose activity is characterized by a great variability in the general population. This variability can be explained, in part, by genetic and environmental factors The classification of phenotypes associated with CYP2C19 has evolved over time. Today, five distinct phenotypes are used to characterize this variability: the slow metabolizer (SM) phenotype, the intermediate metabolizer (IM) phenotype, the normal metabolizer (NM) phenotype, the fast metabolizer (RM) phenotype and finally the ultra-fast metabolizer (UM) phenotype. (UM) phenotype.
Although directly measurable with test substances, CYP2C19 phenotypes are often assigned on the basis of genotype. They may be impacted by intrinsic (e.g., comorbidities) or extrinsic (e.g., co-medications) factors. Phenoconversion or phenotypic change is the phenomenon by which an individual switches from one phenotype to another due to an environmental influence such as a drug interaction. However, genotype is likely to influence the degree of response to a drug interaction. Vulnerability to phenoconversion therefore differs according to the genotype of the individual.
The purpose of our study is to determine whether individuals genetically MR, NM and IM have the same vulnerability to phenoconversion. Thus, the magnitude of the response to CYP2C19 inhibition will be studied in these 3 groups of individuals (NM:*1/*1, RM:*1/*17 and IM:*1/*2-*2/*17). Inhibition will be studied in two steps, using a strong (fluvoxamine) and a weak (voriconazole) inhibitor of CYP2C19.
Detailed description
Phase 1, open-label, parallel study in healthy volunteers selected according to their genotypic belonging to one of the three study groups.
Volunteers are included in the study and go through a buccal swab for genotyping, allowing their allocation into 3 groups according to their CYP2C19 genotype (RM: *1/*17 - NM: *1/*1 - IM: *1/*2 and *2/*17).
Following this step, volunteers have an inclusion session to determine if they meet the inclusion and non-exclusion criteria for the study.
The included volunteers will participate in three study sessions will take place.
Session 1 (control session): administration of 10mg of omeprazole for CYP2C19 phenotyping Session 2: same as session 1 with a prior intake of voriconazole 400 mg (weak inhibitor of CYP2C19 2 hours before omeprazole intake) Session 3: same as session 1 with a prior intake of fluvoxamine (strong CYP2C19 inhibitor, 12 h before and 2 h before taking the omeprazole)
At each session, dried blood spot (DBS) samples will be collected before the intake of the omeprazole (T0) and then at 2, 3, 6 and 8 hours after taking the capsule.
A wash-out period of minimum 3 days will be observed between session 1 and 2 and of minimum 1 week will be observed between sessions 2 and 3.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- The study will include 3 distinct CYP2C19 genotype groups that will constitute the 3 arms of the study. For each volunteer, the study will consist of 3 sessions. Same drugs will be administered to the 3 arms of the study.
| Arm | Type | Receives |
|---|---|---|
| CYP2C19 Rapid Metabolizers (RM) | Experimental | Drug: Voriconazole 200mg, Drug: FluvoxaMINE 50 Mg Oral Tablet, Drug: Omeprazole 10 MG Oral TabletCYP2C19 rapid metabolizers (RM) are characterized by one normal function allele and one increased function allele |
| CYP2C19 Normal metabolizers (NM) | Experimental | Drug: Voriconazole 200mg, Drug: FluvoxaMINE 50 Mg Oral Tablet, Drug: Omeprazole 10 MG Oral TabletCYP2C19 normal metabolizers (NMs) harboring two normal function alleles defined by the lack of any characterized polymorphisms. |
| CYP2C19 Intermediate metabolizers (IM) | Experimental | Drug: Voriconazole 200mg, Drug: FluvoxaMINE 50 Mg Oral Tablet, Drug: Omeprazole 10 MG Oral TabletCYP2C19 intermediate metabolizers (IMs) are characterized by the presence of one normal function allele and one no function allele or one no function allele and one increased function allele. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Healthy men and women ≥ 18 years old
- Understanding of French language and able to give a written consent
- Reliable contraception during the whole study, including a barrier method
- CYP2C19 genotype associated to the RM (*1/*17) , NM(*1/*1) AND IM(*1/*2-*2/*17) activity groups
Key exclusion criteria (13 listed)
- 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 Pharmacoloy and Toxicology, HUG and on the investigator's knowledge)
- History of liver transplantation
- Alcohol intake during fluvoxamine intake
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 |
|---|---|---|
| Voriconazole 200mgAlso: J02AC03Voriconazole is a weak CYP2C19 inhibitor. It is used in study session 2 to study the impact of a weak inhibitor on the phenotype switch among the different genotypes included in the study. | Drug | CYP2C19 Intermediate metabolizers (IM), CYP2C19 Normal metabolizers (NM), CYP2C19 Rapid Metabolizers (RM) |
| FluvoxaMINE 50 Mg Oral TabletAlso: N06AB08Fluvoxamine is a strong CYP2C19 inhibitor. It is used in study session 3 to study the impact of a strong inhibitor on the phenotype switch among the different genotypes included in the study. | Drug | CYP2C19 Intermediate metabolizers (IM), CYP2C19 Normal metabolizers (NM), CYP2C19 Rapid Metabolizers (RM) |
| Omeprazole 10 MG Oral TabletAlso: A02BC01Omeprazole is a CYP2C19 probe substrate. It is used in the study as a tool for CYP2C19 phenotyping at each of the sessions. | Drug | CYP2C19 Intermediate metabolizers (IM), CYP2C19 Normal metabolizers (NM), CYP2C19 Rapid Metabolizers (RM) |
Primary outcome
Phenoconversion rate
Time frame: 2 months
The proportion of volunteers in each group who acquire a phenotype switch such as from NM to PM after pre-treatment by voriconazole and fluvoxamine (weak and strong inhibitors, respectively)
4 secondary outcomes
AUC assessment
Time frame: 1 year
CL assessment
Time frame: 1 year
Cmax assessment
Time frame: 1 year
Tmax assessment
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2022.
- Individual participant dataSharing planned: No
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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.
Caroline Samer, Prof principal investigator
Division of Clinical Pharmacology and Toxicology, Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals
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 Voriconazole 200mg, FluvoxaMINE 50 Mg Oral Tablet and Omeprazole 10 MG Oral Tablet in people with Healthy, run by University Hospital, Geneva 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 4 inclusion and 13 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: status not confirmed, as of the sponsor's last update on 3 Nov 2022. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Youssef Daali, Prof (022395430, Youssef.daali@hcuge.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phenoconversion rate (time frame: 2 months). 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 3 Nov 2022.