Evaluation of the Potential Pharmacokinetic Interactions Between Probe Drugs in the Geneva Phenotyping Cocktail

Drug Interaction Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02391688
• Other study ID #: 14-061
• 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
• 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

Related Conditions & MeSH terms

• Drug Interaction

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