Ignite Creation Date:
2025-12-24 @ 5:05 PM
Ignite Modification Date:
2026-02-12 @ 11:10 AM
Study NCT ID:
NCT02873650
Status:
TERMINATED
Last Update Posted:
2020-12-08
First Post:
2016-08-16
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Pharmacokinetics of Dabrafenib in Subjects With Hepatic Impairment
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'C561627', 'term': 'dabrafenib'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'open-label, parallel group'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 5}}, 'statusModule': {'whyStopped': 'Study was terminated due to continued enrolment difficulties.', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2016-12-20', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-04', 'completionDateStruct': {'date': '2019-04-08', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-12-06', 'studyFirstSubmitDate': '2016-08-16', 'studyFirstSubmitQcDate': '2016-08-16', 'lastUpdatePostDateStruct': {'date': '2020-12-08', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2016-08-19', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2018-10-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Maximum plasma concentration (Cmax)', 'timeFrame': 'Predose through 96 hours postdose'}, {'measure': 'Area under the curve (AUClast)', 'timeFrame': 'Predose through 96 hours postdose'}, {'measure': 'Area under the curve (AUFinf)', 'timeFrame': 'Predose through 96 hours postdose'}, {'measure': 'Systemic drug clearance (CL/F)', 'timeFrame': 'Predose through 96 hours postdose'}, {'measure': 'Time to reach maximum concentration (Tmax)', 'timeFrame': 'Predose through 96 hours postdose'}, {'measure': 'Terminal elimination rate (Lambda_z)', 'timeFrame': 'Predose through 96 hours postdose'}, {'measure': 'Elimination half-life (T1/2)', 'timeFrame': 'Predose through 96 hours postdose'}, {'measure': 'Volume of distribution (Vz/F)', 'timeFrame': 'Predose through 96 hours postdose'}], 'secondaryOutcomes': [{'measure': 'Number of subjects with adverse events', 'timeFrame': 'Time of study drug administration through 30 days postdose'}, {'measure': 'Number of subjects with abnormal lab values related to study drug', 'timeFrame': 'Time of study drug administration through 30 days postdose'}, {'measure': 'Number of subjects with abnormal blood pressure related to study drug', 'timeFrame': 'Time of study drug administration through 30 days postdose'}, {'measure': 'Number of subjects with abnormal pulse rate related to study drug', 'timeFrame': 'Time of study drug administration through 30 days postdose'}, {'measure': 'Number of subjects with abnormal respiratory rate related to study drug', 'timeFrame': 'Time of study drug administration through 30 days postdose'}, {'measure': 'Number of subjects with abnormal body temperature related to study drug', 'timeFrame': 'Time of study drug administration through 30 days postdose'}, {'measure': 'Changes in electrocardiogram (ECG)', 'timeFrame': 'Time of study drug administration through 30 days postdose'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Hepatic impairment', 'Healthy volunteers', 'Clinical pharmacology study', 'DRB436', 'dabrafenib', 'normal hepatic function', 'impaired hepatic function'], 'conditions': ['Hepatic Impairment']}, 'referencesModule': {'seeAlsoLinks': [{'url': 'https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17618', 'label': 'Related Info'}]}, 'descriptionModule': {'briefSummary': 'To characterize the pharmacokinetics and safety of dabrafenib following a single 100 mg oral dose in subjects with moderate and severe hepatic impairment.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion criteria (for all subjects)\n\n* Male and/or female subjects 18-75 years of age\n* Females must be of non-childbearing potential . All non-postmenopausal females must have a confirmed negative serum pregnancy\n* Subjects in good health condition as determined by no clinically significant findings from medical history and physical examination.\n* Body mass index (BMI) between ≥18.0 and ≤38.0 kg/m2, with body weight ≥ 50 kg and no more than 140 kg\n* Laboratory values must be within normal limits (correction allowed) or considered clinically insignificant\n* Do not participate in any other clinical trials with a BRAF or other RAF inhibitors\n\nAdditional inclusion criteria for patients with normal hepatic function (Control group):\n\n* Absence of clinically significant deviation from normal in medical history, physical examination, vital signs, electrocardiograms and clinical laboratory determinations.\n* Must match to at least one hepatic impairment subject by age, gender and bodyweight\n\nAdditional inclusion criteria for hepatic impaired subjects:\n\n* Confirmed hepatic disease\n* Stable Child-Pugh status within 28 days prior to dosing.\n\nExclusion criteria for all subjects\n\n* Participation in any clinical investigation within 4 weeks prior to dosing\n* Significant acute illness within the two weeks prior to dosing\n* History of immunodeficiency diseases, including a positive HIV\n* History of malignancy of any organ system, treated or untreated, within 5 years\n* Any prior history of keratoacanthoma and/or cutaneous squamous cell carcinoma\n* A known diagnosis of any of the RASopathies, such as NF-1, Noonan syndrome, or related conditions.\n* History of drug or alcohol abuse within the 6 months prior to dosing\n* Smoking: urine cotinine levels below 500 ng/mL on Day -1.\n* Use of drugs known to affect CYP3A4 and/or CYP2C8 including both (strong or moderate) inhibitors and inducers, within 7 days prior to dosing\n* Administration of medications that prolong the QT interval within 4 weeks prior to dosing and until EOT.\n* History or current diagnosis of cardiac disease indicating significant risk of safety\n* Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs.\n\nAdditional exclusion criteria for healthy subjects (control group):\n\n* Clinical evidence of liver disease or liver injury\n* History or presence of renal impairment as indicated by abnormal creatinine or BUN values\n* A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody\n\nAdditional exclusion criteria for subjects with hepatic impairment:\n\n* Alcohol or drug abuse within one month prior to dosing or evidence of such\n* History of liver transplantation at any time in the past and is on immunosuppressant therapy.\n* Encephalopathy Grade 3 or worse within 28 days of dosing.\n* History of surgical portosystemic shunt.\n* Life expectancy ≤3 months\n\nOther protocol-defined inclusion/exclusion may apply.'}, 'identificationModule': {'nctId': 'NCT02873650', 'briefTitle': 'Pharmacokinetics of Dabrafenib in Subjects With Hepatic Impairment', 'organization': {'class': 'INDUSTRY', 'fullName': 'Novartis'}, 'officialTitle': 'A Phase I, Open Label, Multicenter, Single Dose Study to Evaluate the Pharmacokinetics of Dabrafenib in Healthy Subjects With Normal Hepatic Function and Subjects With Impaired Hepatic Function', 'orgStudyIdInfo': {'id': 'CDRB436A2107'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Group 1 - Control group', 'interventionNames': ['Drug: dabrafenib']}, {'type': 'EXPERIMENTAL', 'label': 'Group 2-Moderate hepatic impairment', 'interventionNames': ['Drug: dabrafenib']}, {'type': 'EXPERIMENTAL', 'label': 'Group 3-Severe hepatic impairment', 'interventionNames': ['Drug: dabrafenib']}], 'interventions': [{'name': 'dabrafenib', 'type': 'DRUG', 'otherNames': ['DRB436'], 'description': 'Single dose of 100 mg dabrafenib on Day 1', 'armGroupLabels': ['Group 1 - Control group', 'Group 2-Moderate hepatic impairment', 'Group 3-Severe hepatic impairment']}]}, 'contactsLocationsModule': {'locations': [{'zip': '900017', 'city': 'Los Angeles', 'state': 'California', 'country': 'United States', 'facility': 'American Institute of Research', 'geoPoint': {'lat': 34.05223, 'lon': -118.24368}}, {'zip': '32713', 'city': 'DeBary', 'state': 'Florida', 'country': 'United States', 'facility': 'Omega Research Consultants LLC', 'geoPoint': {'lat': 28.88305, 'lon': -81.30868}}, {'zip': '08009', 'city': 'Berlin', 'state': 'New Jersey', 'country': 'United States', 'facility': 'Hassman Research Institute', 'geoPoint': {'lat': 39.79123, 'lon': -74.92905}}, {'zip': '27612', 'city': 'Raleigh', 'state': 'North Carolina', 'country': 'United States', 'facility': 'Wake Research Associates Oncology', 'geoPoint': {'lat': 35.7721, 'lon': -78.63861}}], 'overallOfficials': [{'name': 'Novartis Pharmaceuticals', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Novartis Pharmaceuticals'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Novartis Pharmaceuticals', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}