Ignite Creation Date:
2025-12-24 @ 6:28 PM
Ignite Modification Date:
2025-12-28 @ 3:09 PM
Study NCT ID:
NCT01769768
Status:
COMPLETED
Last Update Posted:
2020-12-19
First Post:
2013-01-15
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Phase I Study to Evaluate the Effect of LDE225 on the Pharmacokinetics of Bupropion and Warfarin in Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'C561435', 'term': 'sonidegib'}, {'id': 'D016642', 'term': 'Bupropion'}], 'ancestors': [{'id': 'D011427', 'term': 'Propiophenones'}, {'id': 'D007659', 'term': 'Ketones'}, {'id': 'D009930', 'term': 'Organic Chemicals'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 114}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2013-04'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-02', 'completionDateStruct': {'date': '2016-08', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-12-16', 'studyFirstSubmitDate': '2013-01-15', 'studyFirstSubmitQcDate': '2013-01-15', 'lastUpdatePostDateStruct': {'date': '2020-12-19', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2013-01-17', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2016-08', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Pharmacokinetics (PK) parameter AUClast for S- and R-warfarin', 'timeFrame': '7 days', 'description': 'Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration'}, {'measure': 'PK parameter AUClast for bupropion', 'timeFrame': '7 days', 'description': 'Pharmacokinetics bupropion : Maximum observed plasma concentration after drug administration'}, {'measure': 'PK parameter AUCinf for bupropion', 'timeFrame': '7 days', 'description': 'Pharmacokinetics of bupropion : Maximum observed plasma concentration after drug administration'}, {'measure': 'PK parameter AUCinf for S- and R-warfarin', 'timeFrame': '7 days', 'description': 'Pharmacokinetics of warfarin and bupropion : Maximum observed plasma concentration after drug administration'}, {'measure': 'PK parameter Cmax for S- and R-warfarin', 'timeFrame': '7 days', 'description': 'Pharmacokinetics of warfarin : Maximum observed plasma concentration after drug administration'}, {'measure': 'PK parameters Cmax for bupropion', 'timeFrame': '7 days', 'description': 'Pharmacokinetics of Bupropion : Maximum observed plasma concentration after drug administration'}], 'secondaryOutcomes': [{'measure': 'effects of LDE225 on the pharmacodynamic activity of warfarin', 'timeFrame': '7 days', 'description': 'INR parameter (International Normalized Ratio) will be assessed to evaluate the pharmacodynamic effect of warfarin.'}, {'measure': 'safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin', 'timeFrame': '28 days cycles', 'description': 'safety laboratory parameters, adverse event reports, changes in vital signs, changes in physical examination parameters'}, {'measure': 'evaluate the preliminary evidence of anti-tumor activity of LDE225 in patients with advanced solid tumors', 'timeFrame': 'every other cycle', 'description': 'CT or MRI imaging parameters to determine the objective response rate according to RECIST 1.1 (Response Evaluation Criteria In Solid Tumors)'}, {'measure': 'assess the effect of LDE225 treatment on cardiac function', 'timeFrame': 'screening, cycle 4 and EOT', 'description': 'ECGs will be performed to determine the effect of LDE on the cardiac function.'}, {'measure': 'effects of LDE225 on the pharmacodynamic activity of warfarin', 'timeFrame': '7 days', 'description': 'PT (Prothrombin time) parameter will be assessed to evaluate the pharmacodynamic effect of warfarin.'}, {'measure': 'safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin', 'timeFrame': '28 days cycles', 'description': 'safety laboratory parameters'}, {'measure': 'safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin', 'timeFrame': '28 days cycles', 'description': 'adverse event reports'}, {'measure': 'safety of LDE225 when administered alone and concomitantly with either bupropion or warfarin', 'timeFrame': '28 days cycles', 'description': 'changes in vital signs'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Adults, Hh (Hedgehog) pathway inhibitor, LDE225, Warfarin, Bupropion, advanced solid tumor, drug-drug interaction, pharmacokinetic'], 'conditions': ['Advanced Solid Tumor']}, 'referencesModule': {'references': [{'pmid': '32736411', 'type': 'DERIVED', 'citation': "Pooler DB, Ness DB, Sarantopoulos J, Squittieri N, Ravichandran S, Britten CD, Amaravadi RK, Vaishampayan U, LoRusso P, Shapiro GI, Olszanski AJ, Perez R, Gutierrez M, O'Rourke MA, Chung V, Lee JJ, Lewis LD. The effect of sonidegib (LDE225) on the pharmacokinetics of bupropion and warfarin in patients with advanced solid tumours. Br J Clin Pharmacol. 2021 Mar;87(3):1291-1302. doi: 10.1111/bcp.14508. Epub 2020 Aug 20."}], 'seeAlsoLinks': [{'url': 'https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=16289', 'label': 'Results for CLDE225A2112 can be found on the Novartis Clinical Trial Results Website'}]}, 'descriptionModule': {'briefSummary': 'This is a multi center, open-label study to evaluate the drug-drug interaction of LDE225 on the PK of bupropion and warfarin patients with advanced solid tumors. Subjects will receive 800mg daily of LDE225 and two separate doses of either bupropion or warfarin.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Adults\n* Patients with cytopathologically or histopathologically confirmed diagnosis of an advanced solid tumor which has progressed despite standard therapy, or for which no standard therapy exists or patients with locally advanced or metastatic basal cell carcinoma who are not amendable or eligible for standard therapy.\n* Protocol-defined renal , liver and bone marrow function\n\nExclusion Criteria:\n\n* CNS (Central Nervous System) tumors as well as history of brain metastases\n* Systemic anticancer treatment (including biologic therapy/antibodies) within 2 weeks before first dose of study treatment (6 weeks for nitrosourea, mitomycin, and monoclonal antibodies).\n* Radiation therapy within 4 weeks before first dose\n* Investigational agents within 4 weeks before start of study therapy\n* Patients with known allergy/hypersensitivity to warfarin or bupropion and/or related compounds\n* Patients with a history of/or active bleeding disorders\n* Patients receiving treatment with vitamin K, Coumadin or other agents containing warfarin and heparin. Heparin flush to maintain patency of a central venous access device is allowed.\n* Patients receiving treatment with bupropion.\n* Patients who have neuromuscular disorders that are associated with elevated CK (Creatine phosphokinase) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).\n* Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B or C (testing is not mandatory for study entry)\n* Patients currently receiving systemic corticosteroids\n\nOther protocol-defined inclusion/exclusion criteria may apply'}, 'identificationModule': {'nctId': 'NCT01769768', 'briefTitle': 'Phase I Study to Evaluate the Effect of LDE225 on the Pharmacokinetics of Bupropion and Warfarin in Patients', 'organization': {'class': 'INDUSTRY', 'fullName': 'Novartis'}, 'officialTitle': 'A Phase Ib, Multi-center, Two Parallel Group, Open-label, Drug-drug Interaction Study to Assess the Effect of LDE225 on the Pharmacokinetics of Bupropion and Warfarin in Patients With Advanced Solid Tumors', 'orgStudyIdInfo': {'id': 'CLDE225A2112'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'LDE225+Warfarin', 'description': 'At least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the warfarin group.', 'interventionNames': ['Drug: LDE225', 'Drug: Wafarin']}, {'type': 'EXPERIMENTAL', 'label': 'LDE225+Bupropion', 'description': 'At least 15 evaluable patients with advanced solid tumors will be enrolled into the study into the Bupropion group', 'interventionNames': ['Drug: LDE225', 'Drug: Bupropion']}], 'interventions': [{'name': 'LDE225', 'type': 'DRUG', 'description': 'LDE225 800 mg once daily dosing will begin on Cycle 1 Day 1 of a 28-day cycle.Treatment with LDE225 for both groups will continue until the patient experiences unacceptable toxicity that precludes further treatment, disease progression, withdrawal of consent and/or at the discretion of the investigator.', 'armGroupLabels': ['LDE225+Bupropion', 'LDE225+Warfarin']}, {'name': 'Wafarin', 'type': 'DRUG', 'description': '15 mg single dose of warfarin (oral tablet) will be given to patients.', 'armGroupLabels': ['LDE225+Warfarin']}, {'name': 'Bupropion', 'type': 'DRUG', 'description': '75 mg single dose of bupropion(oral tablet, from an immediate release formulation) will be given to patients', 'armGroupLabels': ['LDE225+Bupropion']}]}, 'contactsLocationsModule': {'locations': [{'zip': '91010', 'city': 'Duarte', 'state': 'California', 'country': 'United States', 'facility': 'City of Hope National Medical Center Oncology', 'geoPoint': {'lat': 34.13945, 'lon': -117.97729}}, {'zip': '66160', 'city': 'Kansas City', 'state': 'Kansas', 'country': 'United States', 'facility': 'University of Kansas Medical Center CBYM338B2203', 'geoPoint': {'lat': 39.11417, 'lon': -94.62746}}, {'zip': '02114', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Massachusetts General Hospital Dana-Farber Cancer Institute', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '48201', 'city': 'Detroit', 'state': 'Michigan', 'country': 'United States', 'facility': 'Karmanos Cancer Institute', 'geoPoint': {'lat': 42.33143, 'lon': -83.04575}}, {'zip': '03756', 'city': 'Lebanon', 'state': 'New Hampshire', 'country': 'United States', 'facility': 'Dartmouth Hitchcock Medical Center Dartmouth-Hitchcock Med Ctr', 'geoPoint': {'lat': 43.64229, 'lon': -72.25176}}, {'zip': '07601', 'city': 'Hackensack', 'state': 'New Jersey', 'country': 'United States', 'facility': 'Hackensack University Medical Center Dept.of HackensackUniv.MedCtr.', 'geoPoint': {'lat': 40.88593, 'lon': -74.04347}}, {'zip': '19104', 'city': 'Philadelphia', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'University of Pennsylvania--Abramson Cancer Center Abramson Cancer Center', 'geoPoint': {'lat': 39.95238, 'lon': -75.16362}}, {'zip': '19111-2497', 'city': 'Philadelphia', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'Fox Chase Cancer Center', 'geoPoint': {'lat': 39.95238, 'lon': -75.16362}}, {'zip': '15232', 'city': 'Pittsburgh', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'University of Pittsburgh Cancer Institute UPMC Cancer Pavilion', 'geoPoint': {'lat': 40.44062, 'lon': -79.99589}}, {'zip': '29425', 'city': 'Charleston', 'state': 'South Carolina', 'country': 'United States', 'facility': 'Medical University of South Carolina Dept.of Neurosciences/MS Ctr.', 'geoPoint': {'lat': 32.77632, 'lon': -79.93275}}, {'zip': '29605', 'city': 'Greenville', 'state': 'South Carolina', 'country': 'United States', 'facility': 'Cancer Centers of the Carolinas SC', 'geoPoint': {'lat': 34.85262, 'lon': -82.39401}}, {'zip': '78229', 'city': 'San Antonio', 'state': 'Texas', 'country': 'United States', 'facility': 'Utah Health Science Center at San Antonio', 'geoPoint': {'lat': 29.42412, 'lon': -98.49363}}, {'zip': '84112', 'city': 'Salt Lake City', 'state': 'Utah', 'country': 'United States', 'facility': 'University of Utah / Huntsman Cancer Institute', 'geoPoint': {'lat': 40.76078, 'lon': -111.89105}}], 'overallOfficials': [{'name': 'Novartis Pharmaceuticals', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Novartis Pharmaceuticals'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Novartis Pharmaceuticals', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}