KF2022#4-trial: Effects of a Beta Blocker and NSAID on CYP Mediated Drug Metabolism
NCT Number: NCT06566794
Acronym: KF2022#4
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Drug Interaction
Interventions: DRUG: Caffeine Tablet|DRUG: Bupropion Hydrochloride Capsels|DRUG: Repaglinide Capsels|DRUG: Flurbiprofen Capsels|DRUG: Omeprazole 10 MG|DRUG: Dextromethorphan Oral Solution|DRUG: Midazolam oral solution|DRUG: Simvastatin tablets|DRUG: Placebo|DRUG: Carvedilol|DRUG: Diclofenac
Sponsor: Helsinki University Central Hospital
Collaborators: University of Helsinki
Sex: ALL
Age: ADULT
Enrollment: 12
Study Design: Allocation: RANDOMIZED|Intervention Model: CROSSOVER|Masking: NONE|Primary Purpose: BASIC_SCIENCE
Start Date: 2024-08-20
Completion Date: 2025-12-31
Locations: Department of Clinical Pharmacology, Helsinki, Finland

Summary:
Carvedilol is a non-selective beta-blocker in common clinical use, used to treat hypertension, heart failure, and angina pectoris symptoms associated with coronary artery disease. Diclofenac is a non-selective anti-inflammatory drug in general use, which is used to treat rheumatic diseases, osteoarthritis, musculoskeletal pain conditions, menstrual pains and migraines, among others. In our recent experiments involving liver cell enzymes, both carvedilol and diclofenac were found to inhibit several cytochrome P450 (CYP) enzymes central to drug metabolism, potentially leading to adverse drug interactions with other drugs metabolized by the same enzyme. The purpose of this study is to investigate the effects of the use of carvedilol and diclofenac on the activity of key CYP enzymes in drug metabolism in healthy volunteers using a low-dose model drug combination covering seven CYP enzymes.

In an open three-phase, randomized, crossover study with 12 healthy volunteers, the subjects will receive a drug combination of caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam and simvastatin and as a premedication either placebo, carvedilol or diclofenac. Blood samples will be collected and carvedilol, diclofenac, caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam and simvastatin pharmacokinetics will be monitored up to 23 hours post dose.

Primary Outcome Measures: Area under the plasma concentration - time curve of carvedilol, diclofenac, caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam and simvastatin, Prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 23 hours after administration the drugs.
Secondary Outcome Measures: Peak plasma concentration for carvedilol, diclofenac, caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam, simvastatin and their metabolites., Prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 23 hours after administration the drugs.|Half-life for carvedilol, diclofenac, caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam, simvastatin and their metabolites., Prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 23 hours after administration the drugs.|Time to peak plasma concentration for carvedilol, diclofenac, caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam, simvastatin and their metabolites., Prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 23 hours after administration the drugs.|Fractional areas under concentration-time curve (AUC) for carvedilol, diclofenac, caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam, simvastatin and their metabolites., Prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 23 hours after administration the drugs.|Areas under concentration-time curve (AUC) for carvedilol, diclofenac, caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam, simvastatin and their metabolites., Prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 23 hours after administration the drugs.