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

NCT ID: NCT02391688

Last Updated: 2017-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2015-04-30

Brief 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.

Conditions

Drug Interaction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Treatment A

Oral intake of:

caffeine 50 mg dextromethorphan 10 mg omeprazole 10 mg flurbiprofen 10 mg midazolam 1 mg

Group Type: EXPERIMENTAL

Caffeine, omeprazole, flurbiprofen, dextromethorphan, midazolam

Intervention Type: DRUG

Treatment B

Oral intake of:

fexofenadine 25 mg

Group Type: EXPERIMENTAL

Fexofenadine

Intervention Type: DRUG

Treatment C

Oral intake of:

bupropion 20 mg

Group Type: EXPERIMENTAL

Bupropion

Intervention Type: DRUG

Treatment D

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

Group Type: EXPERIMENTAL

Caffeine, omeprazole, flurbiprofen, dextromethorphan, midazolam

Intervention Type: DRUG

Bupropion

Intervention Type: DRUG

Fexofenadine

Intervention Type: DRUG

Interventions

Caffeine, omeprazole, flurbiprofen, dextromethorphan, midazolam

Intervention Type: DRUG

Bupropion

Intervention Type: DRUG

Fexofenadine

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Jules Desmeules

OTHER

Sponsor Role: lead

Responsible Party

Jules Desmeules

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Centre de Recherche Clinique, HUG, Rue Gabrielle Perret-Gentil 4

Geneva, , Switzerland

Countries

Switzerland

Other Identifiers

14-061

Identifier Type: -

Identifier Source: org_study_id