Overview

This trial is active, not recruiting.

Condition drug interaction
Treatments caffeine, omeprazole, flurbiprofen, dextromethorphan, midazolam, bupropion, fexofenadine
Phase phase 1
Sponsor Jules Desmeules
Start date November 2014
End date April 2015
Trial size 30 participants
Trial identifier NCT02391688, 14-061

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model crossover assignment
Masking open label
Primary purpose diagnostic
Arm
(Experimental)
Oral intake of: caffeine 50 mg dextromethorphan 10 mg omeprazole 10 mg flurbiprofen 10 mg midazolam 1 mg
caffeine, omeprazole, flurbiprofen, dextromethorphan, midazolam
(Experimental)
Oral intake of: fexofenadine 25 mg
fexofenadine
(Experimental)
Oral intake of: bupropion 20 mg
bupropion
(Experimental)
Oral Intake of Geneva cocktail (A+B+C): caffeine 50 mg dextromethorphan 10 mg omeprazole 10 mg flurbiprofen 10 mg midazolam 1 mg fexofenadine 25 mg bupropion 20 mg
caffeine, omeprazole, flurbiprofen, dextromethorphan, midazolam
bupropion
fexofenadine

Primary Outcomes

Measure
Area under the capillary blood concentration-time curve (AUC) of caffeine
time frame: 0, 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Area under the capillary blood concentration-time curve (AUC) of dextromethorphan
time frame: 0, 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Area under the capillary blood concentration-time curve (AUC) of flurbiprofen
time frame: 0, 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Area under the capillary blood concentration-time curve (AUC) of midazolam
time frame: 0, 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Area under the capillary blood concentration-time curve (AUC) of omeprazole
time frame: 0, 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Area under the capillary blood concentration-time curve (AUC) of fexofenadine
time frame: 0, 0.5, 1, 2, 3, 4, 6, 8 hours post treatment B or D
Area under the capillary blood concentration-time curve (AUC) of bupropion
time frame: 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post treatment C or D

Secondary Outcomes

Measure
Metabolic ratio (MR) of paraxanthine blood concentration /caffeine blood concentration
time frame: 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Metabolic ratio (MR) of dextrorphan blood concentration /dextromethorphan blood concentration
time frame: 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Metabolic ratio (MR) of 4-hydroxyflurbiprofen blood concentration /flurbiprofen blood concentration
time frame: 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Metabolic ratio (MR) of 1-hydroxymidazolam blood concentration /midazolam blood concentration
time frame: 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Metabolic ratio (MR) of 5-hydroxyomeprazole blood concentration /omeprazole blood concentration
time frame: 0.5, 1, 2, 3, 4, 6, 8 hours post treatment A or D
Metabolic ratio (MR) of 4-hydroxybupropion blood concentration /bupropion blood concentration
time frame: 0.5, 1, 2, 3, 4, 6, 8, 12, 24 hours post treatment C or D
Number of adverse events
time frame: at each drug administration day

Eligibility Criteria

Male or female participants from 18 years up to 60 years old.

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

Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by University Hospital, Geneva.