Ignite Creation Date:
2025-12-24 @ 9:09 PM
Ignite Modification Date:
2025-12-30 @ 3:16 PM
Study NCT ID:
NCT01258504
Status:
COMPLETED
Last Update Posted:
2017-05-31
First Post:
2010-12-10
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Influence of CYP3A4-induction by St. John's Wort on the Steady State Pharmacokinetics of Bosentan
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'C422326', 'term': 'Hypericum extract LI 160'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'gerd.mikus@med.uni-heidelberg.de', 'phone': '4962215639197', 'title': 'Prof. Dr. med. Gerd Mikus', 'organization': 'University of Heidelberg'}, 'certainAgreement': {'piSponsorEmployee': True, 'restrictiveAgreement': False}, 'limitationsAndCaveats': {'description': 'Interindividual changes of the interaction were large suggesting that close monitoring of bosentan effects is advisable because in a sizeable fraction of volunteers the exposure to bosentan was reduced.'}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Bosentan After First Dose', 'description': 'bosentan 125 mg p.o. day 1 single dose', 'otherNumAtRisk': 13, 'otherNumAffected': 9, 'seriousNumAtRisk': 13, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Bosentan at Steady-state', 'description': 'bosentan 62.5 mg p.o. b.i.d. day 2-10', 'otherNumAtRisk': 13, 'otherNumAffected': 9, 'seriousNumAtRisk': 13, 'seriousNumAffected': 0}, {'id': 'EG002', 'title': "Bosentan During St John's Wort", 'description': 'bosentan 62.5 mg p.o. b.i.d. day 11-20 SJW 300 mg t.i.d. day 11-20', 'otherNumAtRisk': 13, 'otherNumAffected': 4, 'seriousNumAtRisk': 13, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'feeling of heat', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 13, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 13, 'numAffected': 4}, {'groupId': 'EG002', 'numAtRisk': 13, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'dyspnea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 13, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'increase of alanine aminotransferase', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 13, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'pressure sensation in the head', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 13, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'epigastric pressure sensation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 13, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'nasopharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 13, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 13, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'strained muscle', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 13, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'nasal congestion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 13, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'ocular itching with secretion of tears', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 13, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'AUC of Bosentan', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '13', 'groupId': 'OG001'}, {'value': '13', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan After First Dose', 'description': 'bosentan 125 mg p.o. day 1 single dose'}, {'id': 'OG001', 'title': 'Bosentan at Steady-state', 'description': 'bosentan 62.5 mg p.o. b.i.d. day 2-10'}, {'id': 'OG002', 'title': "Bosentan During St John's Wort", 'description': 'bosentan 62.5 mg p.o. b.i.d. day 11-20 SJW 300 mg t.i.d. day 11-20'}], 'classes': [{'categories': [{'measurements': [{'value': '9540', 'groupId': 'OG000', 'lowerLimit': '7630', 'upperLimit': '12000'}, {'value': '5710', 'groupId': 'OG001', 'lowerLimit': '4530', 'upperLimit': '7200'}, {'value': '5020', 'groupId': 'OG002', 'lowerLimit': '2910', 'upperLimit': '8690'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '0-infinity; during dosing interval', 'unitOfMeasure': 'h*ng/ml', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}, {'type': 'PRIMARY', 'title': 'Cmax of Bosentan', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '13', 'groupId': 'OG001'}, {'value': '13', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan After First Dose', 'description': 'bosentan125 mg p.o. day 1 single dose'}, {'id': 'OG001', 'title': 'Bosentan at Steady-state', 'description': 'bosentan 62.5 mg p.o. b.i.d. day 2-10'}, {'id': 'OG002', 'title': "Bosentan During St John's Wort", 'description': 'bosentan 62.5 mg p.o. b.i.d. day 11-20 SJW 300 mg t.i.d. day 11-20'}], 'classes': [{'categories': [{'measurements': [{'value': '1620', 'groupId': 'OG000', 'lowerLimit': '1170', 'upperLimit': '2240'}, {'value': '1370', 'groupId': 'OG001', 'lowerLimit': '1050', 'upperLimit': '1790'}, {'value': '1280', 'groupId': 'OG002', 'lowerLimit': '707', 'upperLimit': '2300'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'after first dose, at steady-state and during SJW', 'unitOfMeasure': 'ng/ml', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Bosentan', 'description': 'bosentan 125 mg p.o. single dose day 1 bosentan 62.5 mg p.o. b.i.d. day 2-10 bosentan 62.5 mg p.o. b.i.d. day 11-20 SJW 300 mg p.o. t.i.d. day 11-20'}], 'periods': [{'title': 'Bosentan Single Dose', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '13'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '13'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}, {'title': 'Bosentan Steady-state', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '13'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '13'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}, {'title': 'Bosentan and SJW', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '13'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '13'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Bosentan', 'description': 'bosentan 125 mg p.o. day 1 single dose bosentan 62.5 mg p.o. b.i.d. day 2-10 bosentan 62.5 mg p.o. b.i.d. day 11-20 SJW 300 mg p.o. t.i.d. day 11-20'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '35', 'spread': '11', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '12', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Germany', 'categories': [{'measurements': [{'value': '13', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'CASE_CONTROL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 13}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2011-01'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-05', 'completionDateStruct': {'date': '2012-06', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-05-03', 'studyFirstSubmitDate': '2010-12-10', 'resultsFirstSubmitDate': '2014-07-09', 'studyFirstSubmitQcDate': '2010-12-10', 'lastUpdatePostDateStruct': {'date': '2017-05-31', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2015-05-29', 'studyFirstPostDateStruct': {'date': '2010-12-13', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2015-06-02', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2011-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'AUC of Bosentan', 'timeFrame': '0-infinity; during dosing interval'}, {'measure': 'Cmax of Bosentan', 'timeFrame': 'after first dose, at steady-state and during SJW'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Steady-state', 'Bosentan', 'St. Johns Wort'], 'conditions': ['Drug Interactions']}, 'referencesModule': {'references': [{'pmid': '15568889', 'type': 'BACKGROUND', 'citation': 'Dingemanse J, van Giersbergen PL. Clinical pharmacology of bosentan, a dual endothelin receptor antagonist. Clin Pharmacokinet. 2004;43(15):1089-115. doi: 10.2165/00003088-200443150-00003.'}]}, 'descriptionModule': {'briefSummary': "The aim of the present study is to assess the impact of the cytochrome P450 2C9 (CYP2C9) genotype (\\*2 and \\*3 allele versus wild type; \\~3-5% poor metabolisers in Caucasian population) on the pharmacokinetics of bosentan and the impact of CYP3A4-induction by St. John's wort (SJW) on steady state bosentan which is a CYP3A4 inducer itself.", 'detailedDescription': 'We evaluate the effect of SJW on bosentan pharmacokinetics and its relationship to polymorphisms in the CYP2C9 gene known to reduce CYP2C9 activity. This study will be conducted at bosentan steady-state because concentrations decrease in the first 10 days of treatment due to auto-induction of the metabolism.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'healthy subjects', 'healthyVolunteers': True, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Good state of health (physically and mentally)\n* Able to communicate well with the investigator, to understand and comply with the requirements of the study\n* Voluntarily signed informed consent after full explanation of the study to the participant.\n* No clinically relevant findings in any of the investigations of the pre-study examination, especially aminotransferase elevations ≥ 3 × upper limit of normal(ULN). Minor deviations of other laboratory values from normal range may be acceptable, if judged by the investigator to be of no clinical relevance.\n* Known genotype for CYP2C9 polymorphism.\n* Agreement to abstain from alcoholic beverages during the time of the study.\n* Females must agree to use a reliable contraception (Pearl Index \\<1%), e.g. double barrier method.\n\nExclusion Criteria:\n\n* Any regular drug treatment within the last two months, except for oral contraceptives in female volunteers and L-thyroxine.\n* Any intake of a substance known to induce or inhibit drug metabolising enzymes or drug transporters within a period of less than 10 times the respective elimination half-life or 2 weeks, whatever is longer\n* Any participation in a clinical trial within the last month before inclusion\n* Any physical disorder which could interfere with the participant's safety during the clinical trial or with the study objectives\n* Any acute or chronic illness, or clinically relevant findings in the pre-study examination, especially: a) any condition, which could modify absorption, distribution, metabolism, or excretion of the drug regimen under investigation b) Allergies (except for mild forms of hay fever) or history of hypersensitivity reactions\n* Regular smoking\n* Blood donation within 6 weeks before first study day\n* Excessive alcohol drinking (more than approximately 20 g alcohol per day)\n* Inability to communicate well with the investigator due to language problems or poor mental development\n* Inability or unwillingness to give written informed consent\n* Known or planned pregnancy or breast feeding\n* Pre-existing moderate or severe liver impairment"}, 'identificationModule': {'nctId': 'NCT01258504', 'briefTitle': "Influence of CYP3A4-induction by St. John's Wort on the Steady State Pharmacokinetics of Bosentan", 'organization': {'class': 'OTHER', 'fullName': 'Heidelberg University'}, 'officialTitle': "Influence of Cytochrome P450 3A4 (CYP3A4)-Induction by St. John's Wort (SJW) on the Steady State Pharmacokinetics of Bosentan", 'orgStudyIdInfo': {'id': 'K330'}, 'secondaryIdInfos': [{'id': '2010-022328-64', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'label': 'CYP2C9 wild type', 'description': 'CYP2C9 wild type ="extensive metaboliser"\n\n* Administration of bosentan: 1 x 125 mg p.o. on days 1 and 20, 2 x 62.5 mg p.o. on day 2, 2 x 125 mg p.o. on days 3-19\n* Administration of St. Johns Wort: 3 x 300 mg daily p.o. on days 11-19 and 2 x 300 mg on day 20', 'interventionNames': ['Drug: St. Johns Wort']}, {'label': 'CYP2C9 mutant', 'description': 'CYP2C9 \\*2/\\*2 or 2\\*/\\*3 or \\*3/\\*3 = "poor metaboliser"\n\n* Administration of bosentan: 1 x 125 mg p.o. on days 1 and 20, 2 x 62.5 mg p.o. on day 2, 2 x 125 mg p.o. on days 3-19\n* Administration of St. Johns Wort: 3 x 300 mg daily p.o. on days 11-19 and 2 x 300 mg on day 20', 'interventionNames': ['Drug: St. Johns Wort']}], 'interventions': [{'name': 'St. Johns Wort', 'type': 'DRUG', 'otherNames': ['Jarsin'], 'description': '* Administration of bosentan: 1 x 125 mg p.o. on days 1 and 20, 2 x 62.5 mg p.o. on day 2, 2 x 125 mg p.o. on days 3-19.\n* Administration of SJW: 3 x 300 mg daily p.o. on days 11-19 and 2 x 300 mg on day 20', 'armGroupLabels': ['CYP2C9 mutant', 'CYP2C9 wild type']}]}, 'contactsLocationsModule': {'locations': [{'zip': '69120', 'city': 'Heidelberg', 'country': 'Germany', 'facility': 'University Hospital Heidelberg', 'geoPoint': {'lat': 49.40768, 'lon': 8.69079}}], 'overallOfficials': [{'name': 'Gerd Mikus, Prof. Dr.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'deputy head of department'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Gerd Mikus', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Head of Clinical Research Unit', 'investigatorFullName': 'Gerd Mikus', 'investigatorAffiliation': 'Heidelberg University'}}}}