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Endobiotics for Phenotyping of Human Cytochrome P450 Enzymes

NCT04188028 · Status: COMPLETED · Phase: NA · Type: INTERVENTIONAL · Enrollment: 40

Last updated 2022-01-04

No results posted yet for this study

Summary

CYP2D6 metabolizes \~25% of all marketed drugs. There is an important variability in the activity of this enzyme among individuals. The cause of this variability might be environmental, genetic, ethnical or even related to a disease. The administration of a CYP2D6 probe drug (e.g. dextromethorphan) is a good way to characterize CYP2D6 phenotype. Nonetheless, it is relatively invasive and the vulnerable population (e.g. pregnant women) cannot be phenotyped in this manner. Therefore, finding an endogenous substance which is metabolized by CYP2D6 could replace usual phenotyping procedure using a probe drug. This study evaluates the impact of a CYP2D6 inhibitor and of genetic polymorphism on the metabolome of healthy volunteers in order to identify new CYP2D6 biomarkers. To this end, untargeted metabolomics analysis using LC-HRMS will be performed on plasma and urine samples This single-centre open-label clinical trial will include 40 healthy subjects (men and women) between 18 and 65 years. Eligible participants will be assigned to a study group according to their CYP2D6 genotypes: poor metabolizers (PMs) and extensive/ultrarapid metabolizers (EMs-UMs). Two sessions will take place for each subjects.

Session 1: CYP2D6 phenotyping (dextromethorphan 5 mg, single dose) Session 2: idem session 1 with prior uptake of a CYP2D6 inhibitor (paroxetine 10 or 20 mg, one dose a day for 7 days).

In both sessions, urine will be collected up to 24 hours and capillary/venous blood will be sampled before phenotyping for metabolomics analyses. Urine will also be collected for 4 hours after dextromethorphan intake in order to phenotype the CYP2D6 enzyme.

Conditions

  • Healthy

Interventions

DRUG

Dextromethorphan 5 MG

dextromethorphan 5 mg po

DRUG

Paroxetine 10Mg Tablet

Paroxetine 10 mg po

DRUG

Paroxetine 20Mg Tablet

Paroxetine 20 mg po

Sponsors & Collaborators

  • Jules Desmeules

    lead OTHER

Study Design

Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Model
CROSSOVER

Eligibility

Min Age
18 Years
Max Age
65 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2019-01-01
Primary Completion
2019-07-31
Completion
2019-12-31

Countries

  • Switzerland

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04188028 on ClinicalTrials.gov