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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02391688
Other study ID # 14-061
Secondary ID
Status Completed
Phase Phase 1
First received February 19, 2015
Last updated February 6, 2017
Start date November 2014
Est. completion date April 2015

Study information

Verified date February 2017
Source University Hospital, Geneva
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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 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.

When a cocktail approach is used it is important to make sure that no drug-drug interactions occur between the probes within the cocktail. The validation of the lack of interactions, which is the aim of the study, consists of demonstrating that there is no difference in the pharmacokinetic parameters and/or metabolic ratios when a probe is administered alone or as part of the cocktail. The Geneva 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.

Probe and metabolite concentrations will be measured in capillary blood using a dried blood spot (DBS) analysis. To further facilitate sampling, a new simple device will be used to ensure the precision of capillary blood collection.


Recruitment information / eligibility

Status Completed
Enrollment 30
Est. completion date April 2015
Est. primary completion date April 2015
Accepts healthy volunteers Accepts Healthy Volunteers
Gender All
Age group 18 Years to 60 Years
Eligibility Inclusion Criteria:

- Healthy volunteers aged from 18 to 60 years

- BMI between 18 and 27

- Understanding of French language and able to give a written inform consent.

Exclusion Criteria:

- smoker

- pregnant women

- taking drugs which alter cytochrome P450 (CYP) activity

- renal or hepatic impairment

- medical history of chronic alcoholism or abuse of psychoactive drugs

- liver transplantation

- sensitivity to any of the drugs used

- Alteration of hepatic tests, more than 2x normal (aspartate transaminase >100U/L ; alanine transaminase >100 units/L ; gamma-glutamyl transferase >80 units/L ; bilirubin >50µmol/L)

- Presenting genetic polymorphism of poor CYP2C9, CYP2C19, CYP2D6 metabolizer

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Caffeine, omeprazole, flurbiprofen, dextromethorphan, midazolam

Bupropion

Fexofenadine


Locations

Country Name City State
Switzerland Centre de Recherche Clinique, HUG, Rue Gabrielle Perret-Gentil 4 Genève

Sponsors (1)

Lead Sponsor Collaborator
Jules Desmeules

Country where clinical trial is conducted

Switzerland, 

Outcome

Type Measure Description Time frame Safety issue
Other Correlation of drug concentrations (ng/ml) in DBS obtained with two sampling techniques for all administered drugs 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A, B, C and D
Primary Area under the capillary blood concentration-time curve (AUC) of caffeine Comparison of caffeine AUC when treatment A or D is administered 0, 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Primary Area under the capillary blood concentration-time curve (AUC) of dextromethorphan Comparison of dextromethorphan AUC when treatment A or D is administered 0, 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Primary Area under the capillary blood concentration-time curve (AUC) of flurbiprofen Comparison of flurbiprofen AUC when treatment A or D is administered 0, 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Primary Area under the capillary blood concentration-time curve (AUC) of midazolam Comparison of midazolam AUC when treatment A or D is administered 0, 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Primary Area under the capillary blood concentration-time curve (AUC) of omeprazole Comparison of omeprazole AUC when treatment A or D is administered 0, 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Primary Area under the capillary blood concentration-time curve (AUC) of fexofenadine Comparison of fexofenadine AUC when treatment B or D is administered 0, 0.5, 1, 2, 3, 4, 6, 8 hours post treatment B or D
Primary Area under the capillary blood concentration-time curve (AUC) of bupropion Comparison of bupropion AUC when treatment C or D is administered 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post treatment C or D
Secondary Metabolic ratio (MR) of paraxanthine blood concentration /caffeine blood concentration Comparison of paraxanthine/caffeine MRs between treatment A and D 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Secondary Metabolic ratio (MR) of dextrorphan blood concentration /dextromethorphan blood concentration Comparison of dextrorphan/dextromethorphan MRs between treatment A and D 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Secondary Metabolic ratio (MR) of 4-hydroxyflurbiprofen blood concentration /flurbiprofen blood concentration Comparison of 4-hydroxyflurbiprofen/flurbiprofen MRs between treatment A and D 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Secondary Metabolic ratio (MR) of 1-hydroxymidazolam blood concentration /midazolam blood concentration Comparison of 1-hydroxymidazolam/midazolam MRs between treatment A and D 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Secondary Metabolic ratio (MR) of 5-hydroxyomeprazole blood concentration /omeprazole blood concentration Comparison of 5-hydroxyomeprazole/omeprazole MRs between treatment A and D 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Secondary Metabolic ratio (MR) of 4-hydroxybupropion blood concentration /bupropion blood concentration Comparison of 4-hydroxybupropion/bupropion MRs between treatment C and D 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post treatment C or D
Secondary Number of adverse events at each drug administration day
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