Ignite Creation Date:
2025-12-25 @ 1:27 AM
Ignite Modification Date:
2025-12-28 @ 12:06 AM
Study NCT ID:
NCT06566794
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-08-22
First Post:
2024-08-04
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
KF2022#4-trial: Effects of a Beta Blocker and NSAID on CYP Mediated Drug Metabolism
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D002110', 'term': 'Caffeine'}, {'id': 'D016642', 'term': 'Bupropion'}, {'id': 'D002214', 'term': 'Capsules'}, {'id': 'C072379', 'term': 'repaglinide'}, {'id': 'D005480', 'term': 'Flurbiprofen'}, {'id': 'D009853', 'term': 'Omeprazole'}, {'id': 'D003915', 'term': 'Dextromethorphan'}, {'id': 'D012996', 'term': 'Solutions'}, {'id': 'D008874', 'term': 'Midazolam'}, {'id': 'D019821', 'term': 'Simvastatin'}, {'id': 'D013607', 'term': 'Tablets'}, {'id': 'D000077261', 'term': 'Carvedilol'}, {'id': 'D004008', 'term': 'Diclofenac'}], 'ancestors': [{'id': 'D014970', 'term': 'Xanthines'}, {'id': 'D000470', 'term': 'Alkaloids'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D011688', 'term': 'Purinones'}, {'id': 'D011687', 'term': 'Purines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D011427', 'term': 'Propiophenones'}, {'id': 'D007659', 'term': 'Ketones'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D004304', 'term': 'Dosage Forms'}, {'id': 'D004364', 'term': 'Pharmaceutical Preparations'}, {'id': 'D011422', 'term': 'Propionates'}, {'id': 'D000144', 'term': 'Acids, Acyclic'}, {'id': 'D002264', 'term': 'Carboxylic Acids'}, {'id': 'D001713', 'term': 'Biphenyl Compounds'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D053799', 'term': '2-Pyridinylmethylsulfinylbenzimidazoles'}, {'id': 'D013454', 'term': 'Sulfoxides'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D011725', 'term': 'Pyridines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D001562', 'term': 'Benzimidazoles'}, {'id': 'D009019', 'term': 'Morphinans'}, {'id': 'D053610', 'term': 'Opiate Alkaloids'}, {'id': 'D006572', 'term': 'Heterocyclic Compounds, Bridged-Ring'}, {'id': 'D006576', 'term': 'Heterocyclic Compounds, 4 or More Rings'}, {'id': 'D010616', 'term': 'Phenanthrenes'}, {'id': 'D011084', 'term': 'Polycyclic Aromatic Hydrocarbons'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D001569', 'term': 'Benzodiazepines'}, {'id': 'D001552', 'term': 'Benzazepines'}, {'id': 'D008148', 'term': 'Lovastatin'}, {'id': 'D009281', 'term': 'Naphthalenes'}, {'id': 'D011412', 'term': 'Propanolamines'}, {'id': 'D000605', 'term': 'Amino Alcohols'}, {'id': 'D000438', 'term': 'Alcohols'}, {'id': 'D020005', 'term': 'Propanols'}, {'id': 'D000588', 'term': 'Amines'}, {'id': 'D002227', 'term': 'Carbazoles'}, {'id': 'D007211', 'term': 'Indoles'}, {'id': 'D006575', 'term': 'Heterocyclic Compounds, 3-Ring'}, {'id': 'D010648', 'term': 'Phenylacetates'}, {'id': 'D000146', 'term': 'Acids, Carbocyclic'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 12}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2024-08-20', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-08', 'completionDateStruct': {'date': '2025-12-31', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2024-08-20', 'studyFirstSubmitDate': '2024-08-04', 'studyFirstSubmitQcDate': '2024-08-20', 'lastUpdatePostDateStruct': {'date': '2024-08-22', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2024-08-22', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Area under the plasma concentration - time curve of carvedilol, diclofenac, caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam and simvastatin', 'timeFrame': 'Prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 23 hours after administration the drugs.'}], 'secondaryOutcomes': [{'measure': 'Peak plasma concentration for carvedilol, diclofenac, caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam, simvastatin and their metabolites.', 'timeFrame': 'Prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 23 hours after administration the drugs.'}, {'measure': 'Half-life for carvedilol, diclofenac, caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam, simvastatin and their metabolites.', 'timeFrame': 'Prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 23 hours after administration the drugs.'}, {'measure': 'Time to peak plasma concentration for carvedilol, diclofenac, caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam, simvastatin and their metabolites.', 'timeFrame': 'Prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 23 hours after administration the drugs.'}, {'measure': 'Fractional areas under concentration-time curve (AUC) for carvedilol, diclofenac, caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam, simvastatin and their metabolites.', 'timeFrame': 'Prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 23 hours after administration the drugs.'}, {'measure': 'Areas under concentration-time curve (AUC) for carvedilol, diclofenac, caffeine, bupropion, repaglinide, flurbiprofen, omeprazole, dextromethorphan, midazolam, simvastatin and their metabolites.', 'timeFrame': 'Prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 23 hours after administration the drugs.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Drug Interaction']}, 'descriptionModule': {'briefSummary': '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.\n\nIn 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '40 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Written informed consent\n* Age 18-40\n* Healthy\n* Systolic blood pressure ≥110 mmHg\n* Heart rate ≥ 55/min\n* Normal ECG\n* 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.\n\nExclusion Criteria:\n\n* Significant disease\n* Previous or current gastrointestinal bleeding, ulcer or perforation\n* Findings of a medical examination and laboratory tests, which require a more detailed examination of the state of health\n* Smoking\n* Hormonal birth control or other regular medication\n* Pregnancy (current or planned) or nursing\n* Participation in any other studies involving investigational or marketed drug products within three months prior to the entry into this study\n* Donation of blood within three months prior to the entry into this study\n* Significant overweight / small or hard-to-find veins\n* BMI \\< 18.5 kg/m2\n* Insufficient Finnish language skills\n* Hypersensitivity or contraindication to study drugs'}, 'identificationModule': {'nctId': 'NCT06566794', 'acronym': 'KF2022#4', 'briefTitle': 'KF2022#4-trial: Effects of a Beta Blocker and NSAID on CYP Mediated Drug Metabolism', 'organization': {'class': 'OTHER', 'fullName': 'Helsinki University Central Hospital'}, 'officialTitle': 'KF2022#4-tutkimus:Beetasalpaajan ja tulehduskipulääkkeen Vaikutus CYP-entsyymivälitteiseen lääkeainemetaboliaan', 'orgStudyIdInfo': {'id': 'KF2022#4'}, 'secondaryIdInfos': [{'id': '2023-000002-25', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Placebo tablets (2 x Placebo) and 150 ml water at 8.00 a.m. on the study day.\n\nStudy drug doses (caffeine 50 mg, bupropion 20 mg, repaglinide 0,05 mg, flurbiprofen 10 mg, omeprazole 10 mg, dextromethorphan 10 mg, midazolam 1,0 mg, simvastatin 10 mg) and 250 ml water at 9:00 a.m.', 'interventionNames': ['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']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Carvedilol', 'description': 'Carvedilol tablets (2 x Carvedilol STADA 25 mg) and 150 ml water at 8.00 a.m. on the study day.\n\nStudy drug doses (caffeine 50 mg, bupropion 20 mg, repaglinide 0,05 mg, flurbiprofen 10 mg, omeprazole 10 mg, dextromethorphan 10 mg, midazolam 1,0 mg, simvastatin 10 mg) and 250 ml water at 9:00 a.m.', 'interventionNames': ['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: Carvedilol']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Diclofenac', 'description': 'Diclofenac tablet (1 x Voltaren Rapid 50 mg) three times a day around 8.00 a.m., 3.00 p.m. and 9.00 p.m. for three days.\n\nDiclofenac tablet (1 x Voltaren Rapid 50 mg) and 150 ml water at 8.00 a.m., 3.00 p.m. and 9.00 p.m. on the study day (3rd day of diclofenac treatment).\n\nStudy drug doses (caffeine 50 mg, bupropion 20 mg, repaglinide 0,05 mg, flurbiprofen 10 mg, omeprazole 10 mg, dextromethorphan 10 mg, midazolam 1,0 mg, simvastatin 10 mg) and 250 ml water at 9:00 a.m.', 'interventionNames': ['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: Diclofenac']}], 'interventions': [{'name': 'Caffeine Tablet', 'type': 'DRUG', 'otherNames': ['YA Kofeiinitabletti 100 mg, Yliopiston apteekki'], 'description': '0,5 x 100 mg tablet (50 mg caffeine).', 'armGroupLabels': ['Carvedilol', 'Diclofenac', 'Placebo']}, {'name': 'Bupropion Hydrochloride Capsels', 'type': 'DRUG', 'otherNames': ['Bupropion hydrochloride 20 mg caps, HUS Apteekki'], 'description': '1 x 20 mg tablet.', 'armGroupLabels': ['Carvedilol', 'Diclofenac', 'Placebo']}, {'name': 'Repaglinide Capsels', 'type': 'DRUG', 'otherNames': ['Repaglinide 0.05 mg caps, HUS Apteekki'], 'description': '1 x 0,05 mg tablet.', 'armGroupLabels': ['Carvedilol', 'Diclofenac', 'Placebo']}, {'name': 'Flurbiprofen Capsels', 'type': 'DRUG', 'otherNames': ['Flurbiprofen 10 mg caps, HUS Apteekki'], 'description': '1 x 10 mg tablet.', 'armGroupLabels': ['Carvedilol', 'Diclofenac', 'Placebo']}, {'name': 'Omeprazole 10 MG', 'type': 'DRUG', 'otherNames': ['Losec Mups 10 mg enterotablet, AstraZeneca'], 'description': '1 x 10 mg tablet.', 'armGroupLabels': ['Carvedilol', 'Diclofenac', 'Placebo']}, {'name': 'Dextromethorphan Oral Solution', 'type': 'DRUG', 'otherNames': ['Rometor Ratiopharm 2 mg/ml oral solution, Ratiopharm'], 'description': '5,0 ml of 2 mg/ml oral solution (10 mg dextromethorphan).', 'armGroupLabels': ['Carvedilol', 'Diclofenac', 'Placebo']}, {'name': 'Midazolam oral solution', 'type': 'DRUG', 'otherNames': ['Midazolam-Ratiopharm 2 mg/ml oral solution, Ratiopharm'], 'description': '0,5 ml of 2 mg/ml oral solution (1,0 mg midazolam).', 'armGroupLabels': ['Carvedilol', 'Diclofenac', 'Placebo']}, {'name': 'Simvastatin tablets', 'type': 'DRUG', 'otherNames': ['Simvastatin Krka 10 mg tablet, KRKA'], 'description': '1 x 10 mg tablet.', 'armGroupLabels': ['Carvedilol', 'Diclofenac', 'Placebo']}, {'name': 'Placebo', 'type': 'DRUG', 'otherNames': ['Placebo, 9 mm tablet, Yliopiston apteekki'], 'description': '2 x placebo tablets in the Placebo Phase/Arm', 'armGroupLabels': ['Placebo']}, {'name': 'Carvedilol', 'type': 'DRUG', 'otherNames': ['Carvedilol STADA 25 mg tablet, STADA Arzneimittel AG'], 'description': '2 x 25 mg tablets', 'armGroupLabels': ['Carvedilol']}, {'name': 'Diclofenac', 'type': 'DRUG', 'otherNames': ['Voltaren Rapid 50 mg, Novartis Finland Oy'], 'description': '1 x 50 mg tablet (three times daily for three days)', 'armGroupLabels': ['Diclofenac']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Helsinki', 'country': 'Finland', 'contacts': [{'name': 'Janne Backman, MD, PhD', 'role': 'CONTACT', 'email': 'janne.backman@hus.fi', 'phone': '+35894711'}], 'facility': 'Department of Clinical Pharmacology', 'geoPoint': {'lat': 60.16952, 'lon': 24.93545}}], 'centralContacts': [{'name': 'Janne Backman, MD, PhD', 'role': 'CONTACT', 'email': 'janne.backman@hus.fi', 'phone': '+35894711'}, {'name': 'Laura Tervala', 'role': 'CONTACT', 'email': 'laura.tervala@hus.fi', 'phone': '+35894711'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Helsinki University Central Hospital', 'class': 'OTHER'}, 'collaborators': [{'name': 'University of Helsinki', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor, Head physician', 'investigatorFullName': 'Janne Backman', 'investigatorAffiliation': 'Helsinki University Central Hospital'}}}}