NCT06566794

KF2022#4-trial: Effects of a Beta Blocker and NSAID on CYP Mediated Drug Metabolism

KF2022#4-tutkimus:Beetasalpaajan ja tulehduskipulääkkeen Vaikutus CYP-entsyymivälitteiseen lääkeainemetaboliaan

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Helsinki University Central Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 40 Years
• Healthy volunteers: Accepted

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.

Conditions

• Drug Interaction

Interventions

Type	Name	Description
DRUG	Caffeine Tablet	0,5 x 100 mg tablet (50 mg caffeine).
DRUG	Bupropion Hydrochloride Capsels	1 x 20 mg tablet.
DRUG	Repaglinide Capsels	1 x 0,05 mg tablet.
DRUG	Flurbiprofen Capsels	1 x 10 mg tablet.
DRUG	Omeprazole 10 MG	1 x 10 mg tablet.
DRUG	Dextromethorphan Oral Solution	5,0 ml of 2 mg/ml oral solution (10 mg dextromethorphan).
DRUG	Midazolam oral solution	0,5 ml of 2 mg/ml oral solution (1,0 mg midazolam).
DRUG	Simvastatin tablets	1 x 10 mg tablet.
DRUG	Placebo	2 x placebo tablets in the Placebo Phase/Arm
DRUG	Carvedilol	2 x 25 mg tablets
DRUG	Diclofenac	1 x 50 mg tablet (three times daily for three days)

Timeline

• Start date: 2024-08-22
• Primary completion: 2025-01-10
• Completion: 2025-01-10
• First posted: 2024-08-22
• Last updated: 2026-03-06

Locations

1 site across 1 country: Finland