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Completed

NCT Number: NCT06566794

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

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.

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Key information

Conditions

Drug Interaction

Age range

18 year–40 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Department of Clinical Pharmacology

Helsinki, Finland

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Written informed consent
  • Age 18-40
  • Healthy
  • Systolic blood pressure ≥110 mmHg
  • Heart rate ≥ 55/min
  • Normal ECG
  • Accepted results from laboratory tests (blood haemoglobin, basic blood count and blood platelets, alanine aminotransferase, alkaline phosphatase, glutamyl transferase, creatine kinase, creatinine, plasma glucose concentration, plasma potassium and sodium). Negative pregnancy test result (serum human chorionic gonadotropin) for women.

Exclusion criteria

  • Significant disease
  • Previous or current gastrointestinal bleeding, ulcer or perforation
  • Findings of a medical examination and laboratory tests, which require a more detailed examination of the state of health
  • Smoking
  • Hormonal birth control or other regular medication
  • Pregnancy (current or planned) or nursing
  • Participation in any other studies involving investigational or marketed drug products within three months prior to the entry into this study
  • Donation of blood within three months prior to the entry into this study
  • Significant overweight / small or hard-to-find veins
  • BMI < 18.5 kg/m2
  • Insufficient Finnish language skills
  • Hypersensitivity or contraindication to study drugs

Treatment and study plan

Caffeine Tablet

Drug

0,5 x 100 mg tablet (50 mg caffeine).

Other names: YA Kofeiinitabletti 100 mg, Yliopiston apteekki

Bupropion Hydrochloride Capsels

Drug

1 x 20 mg tablet.

Other names: Bupropion hydrochloride 20 mg caps, HUS Apteekki

Repaglinide Capsels

Drug

1 x 0,05 mg tablet.

Other names: Repaglinide 0.05 mg caps, HUS Apteekki

Flurbiprofen Capsels

Drug

1 x 10 mg tablet.

Other names: Flurbiprofen 10 mg caps, HUS Apteekki

Omeprazole 10 MG

Drug

1 x 10 mg tablet.

Other names: Losec Mups 10 mg enterotablet, AstraZeneca

Dextromethorphan Oral Solution

Drug

5,0 ml of 2 mg/ml oral solution (10 mg dextromethorphan).

Other names: Rometor Ratiopharm 2 mg/ml oral solution, Ratiopharm

Midazolam oral solution

Drug

0,5 ml of 2 mg/ml oral solution (1,0 mg midazolam).

Other names: Midazolam-Ratiopharm 2 mg/ml oral solution, Ratiopharm

Simvastatin tablets

Drug

1 x 10 mg tablet.

Other names: Simvastatin Krka 10 mg tablet, KRKA

Placebo

Drug

2 x placebo tablets in the Placebo Phase/Arm

Other names: Placebo, 9 mm tablet, Yliopiston apteekki

Carvedilol

Drug

2 x 25 mg tablets

Other names: Carvedilol STADA 25 mg tablet, STADA Arzneimittel AG

Diclofenac

Drug

1 x 50 mg tablet (three times daily for three days)

Other names: Voltaren Rapid 50 mg, Novartis Finland Oy

Primary outcomes

  1. Area under the plasma concentration - time curve of carvedilol, diclofenac, caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam and simvastatin

    Time frame: Prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 23 hours after administration the drugs.

Secondary outcomes

  1. Peak plasma concentration for carvedilol, diclofenac, caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam, simvastatin and their metabolites.

    Time frame: Prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 23 hours after administration the drugs.

  2. Half-life for carvedilol, diclofenac, caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam, simvastatin and their metabolites.

    Time frame: Prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 23 hours after administration the drugs.

  3. Time to peak plasma concentration for carvedilol, diclofenac, caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam, simvastatin and their metabolites.

    Time frame: Prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 23 hours after administration the drugs.

  4. Fractional areas under concentration-time curve (AUC) for carvedilol, diclofenac, caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam, simvastatin and their metabolites.

    Time frame: Prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 23 hours after administration the drugs.

  5. Areas under concentration-time curve (AUC) for carvedilol, diclofenac, caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam, simvastatin and their metabolites.

    Time frame: Prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 23 hours after administration the drugs.

Sponsors and collaborators

Lead sponsor

Helsinki University Central Hospital

Other

Collaborators

  • University of Helsinki

Registry information

Official study title

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

Acronym: KF2022#4

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Aug 22, 2024
Registry last updated
Mar 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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