Ignite Creation Date:
2025-12-24 @ 7:00 PM
Ignite Modification Date:
2025-12-25 @ 4:33 PM
Study NCT ID:
NCT02624557
Status:
COMPLETED
Last Update Posted:
2020-12-09
First Post:
2015-12-03
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Pharmacokinetic Study of Alpelisib in Subjects With Hepatic Impairment.
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'C585539', 'term': 'Alpelisib'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 23}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2015-12-21', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-05', 'completionDateStruct': {'date': '2017-10-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-12-06', 'studyFirstSubmitDate': '2015-12-03', 'studyFirstSubmitQcDate': '2015-12-03', 'lastUpdatePostDateStruct': {'date': '2020-12-09', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2015-12-08', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2017-10-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Plasma pharmacokinetic (PK) parameter Cmax', 'timeFrame': 'predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose', 'description': 'Measurement of effect of hepatic impairment on PK of alpelisib by assessment of the maximum plasma concentration (PK parameter Cmax). Cmax directly determined from the plasma concentration-time profile.'}, {'measure': 'PK parameter AUClast', 'timeFrame': 'predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose', 'description': 'Measurement of effect of hepatic impairment on PK of alpelisib by assessment of the PK parameter AUClast (area under the concentration-time curve from time zero to the last measurable concentration sampling time). AUC determined from the plasma concentration-time profile using non-compartmental analysis.'}, {'measure': 'PK parameter AUCinf', 'timeFrame': 'predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose', 'description': 'Measurement of effect of hepatic impairment on PK of alpelisib by assessment of the PK parameter AUCinf (area under the concentration-time curve from time zero to infinity ). AUC determined from the plasma concentration-time profile using non-compartmental analysis.'}], 'secondaryOutcomes': [{'measure': 'PK parameter AUC0-t', 'timeFrame': 'predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose', 'description': 'Measurement of effect of hepatic impairment on PK of alpelisib by assessment of the PK parameter AUC0-t (the partial area under the concentration-time curve from time zero to t hours post dose). AUC determined from the plasma concentration-time profile using non-compartmental analysis.'}, {'measure': 'PK parameter tmax', 'timeFrame': 'predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose', 'description': 'Measurement of effect of hepatic impairment on PK of alpelisib by assessment of the PK parameter tmax (time to reach maximum plasma concentration), directly determined from the plasma concentration-time profile.'}, {'measure': 'PK parameter Cl/F', 'timeFrame': 'predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose', 'description': 'Measurement of effect of hepatic impairment on PK of alpelisib by assessment of the PK parameter Cl/F (apparent oral total drug total plasma clearance calculated from steady-state exposure data ). Cl/F determined from the plasma concentration-time profile using non-compartmental analysis.'}, {'measure': 'PK parameter Vz/F', 'timeFrame': 'predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose', 'description': 'Measurement of effect of hepatic impairment on PK of alpelisib by assessment of the PK parameter Vz/F (the apparent volume of distribution during terminal phase). Vz/F determined from the plasma concentration-time profile using non-compartmental analysis.'}, {'measure': 'PK parameter T1/2', 'timeFrame': 'predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose', 'description': 'Measurement of effect of hepatic impairment on PK of alpelisib by assessment of the PK parameter T1/2 (elimination half-life associated with the terminal slope (lambda-z) of a semi logarithmic concentration-time curve). T1/2 determined from the plasma concentration-time profile using non-compartmental analysis.'}, {'measure': 'Relationship between PK parameters Cmax, AUClast, AUCinf and hepatic function parameters', 'timeFrame': 'predose, 30 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 144 hours post-dose', 'description': 'Determination of the relationship between the primary PK parameters Cmax, AUClast, AUCinf and baseline hepatic function parameters total bilirubin, INR and serum albumin.'}, {'measure': 'Adverse events severity and frequency', 'timeFrame': 'Baseline Day 1 to 30 days post-dose', 'description': 'Assessment of safety and tolerability of a single dose alpelisib in hepatic impaired subjects compared with healthy matching control subjects by assessing the frequency and severity of adverse events based on the CTCAE criteria.'}, {'measure': 'Change from baseline in laboratory parameters', 'timeFrame': 'Baseline Day 1 to 30 days post-dose', 'description': 'Assessment of safety and tolerability of a single dose alpelisib in hepatic impaired subjects compared with healthy matching control subjects by assessing the change from baseline in hematological and biochemical laboratory parameters.'}, {'measure': 'Change from baseline in ECG parameters', 'timeFrame': 'Baseline Day 1 to 30 days post-dose', 'description': 'Assessment of safety and tolerability of a single dose alpelisib in hepatic impaired subjects compared with healthy matching control subjects by assessing the change from baseline in ECG parameters.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Hepatic impairment', 'Healthy volunteers', 'Clinical pharmacology study', 'BYL719', 'alpelisib'], 'conditions': ['Hepatic Impairment']}, 'referencesModule': {'seeAlsoLinks': [{'url': 'https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17198', 'label': 'Results for CBYL719A2105 can be found on the Novartis Clinical Trial Results Website'}]}, 'descriptionModule': {'briefSummary': 'To characterize the pharmacokinetics and safety of alpelisib in subjects with hepatic impairment compared to matched healthy control subjects.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': "Inclusion Criteria:\n\n-Other then hepatic impairment, subjects should be in good health as determined by past medical history, physical examination, vital signs, electrocardiogram (except for additional inclusion criteria for hepatic impaired subjects). -Subjects must weigh at least 50 kg and no more than 120 kg and have a body mass index in the range 18.0-36.0 kg/m2.\n\nAdditional criteria for hepatic impaired subjects: -Subjects must have a score clinically determined and calculated as per the Child-Pugh classification and consistent with the degree of hepatic impairment in which study is currently enrolling. -Stable Child-Pugh status within 28 days prior to dosing.\n\nExclusion Criteria: All subjects:\n\n* Subject has received a liver transplant at any time in the past and is on immunosuppressant therapy.\n* Smokers not willing to limit the use of tobacco to 10 cigarettes per day. -Surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject's safety in case of participation in the study. -Use of any herbal medications/supplements.\n\nHistory of acute pancreatitis within 1 year of study entry.\n\nAdditional criteria for subjects with normal liver function:\n\n-Use of any prescription or non-prescription medication. -Positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result.\n\nAdditional criteria for hepatic impaired subjects: -Use of any prescription or non-prescription medication, that has the potential to interact with alpelisb. Concomitant medications without potential to interact with alpelisib must be stable in dose. -Encephalopathy grade 3 or worse. -Total bilirubin \\> 6 mg/dl. Screening or baseline ECG: QTcF\\>480msec for both genders\n\nOther protocol-defined inclusion/exclusion criteria may apply."}, 'identificationModule': {'nctId': 'NCT02624557', 'briefTitle': 'Pharmacokinetic Study of Alpelisib in Subjects With Hepatic Impairment.', 'organization': {'class': 'INDUSTRY', 'fullName': 'Novartis'}, 'officialTitle': 'A Phase 1, Open-label, Single-dose, Multicenter, Parallel Group Study to Assess the Pharmacokinetics and Safety of Alpelisib (BYL719) in Subjects With Hepatic Impairment Compared to Matched Healthy Control Subjects.', 'orgStudyIdInfo': {'id': 'CBYL719A2105'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Moderate hepatic impairment group', 'description': 'Subjects with moderate hepatic impairment with Child-Pugh score 7 - 9', 'interventionNames': ['Drug: Alpelisib']}, {'type': 'EXPERIMENTAL', 'label': 'Severe hepatic impairment group', 'description': 'Subjects with severe hepatic impairment with Child-Pugh score 10 - 15', 'interventionNames': ['Drug: Alpelisib']}, {'type': 'EXPERIMENTAL', 'label': 'Matching healthy control group', 'description': 'Subjects with apparent normal liver function matched to the hepatic impairment subjects by sex, race, age, and weight.', 'interventionNames': ['Drug: Alpelisib']}], 'interventions': [{'name': 'Alpelisib', 'type': 'DRUG', 'description': 'Subjects will receive a single dose of 300 mg alpelisib.', 'armGroupLabels': ['Matching healthy control group', 'Moderate hepatic impairment group', 'Severe hepatic impairment group']}]}, 'contactsLocationsModule': {'locations': [{'zip': '80228', 'city': 'Lakewood', 'state': 'Colorado', 'country': 'United States', 'facility': 'DaVita Clinical Research-Denver', 'geoPoint': {'lat': 39.70471, 'lon': -105.08137}}, {'zip': '33136', 'city': 'Miami', 'state': 'Florida', 'country': 'United States', 'facility': 'University of Miami / Clinical Research Services, Inc.', 'geoPoint': {'lat': 25.77427, 'lon': -80.19366}}, {'zip': '32809', 'city': 'Orlando', 'state': 'Florida', 'country': 'United States', 'facility': 'Orlando Clinical Research Center', 'geoPoint': {'lat': 28.53834, 'lon': -81.37924}}, {'zip': '55404', 'city': 'Minneapolis', 'state': 'Minnesota', 'country': 'United States', 'facility': 'DaVita Clinical Research', 'geoPoint': {'lat': 44.97997, 'lon': -93.26384}}], 'overallOfficials': [{'name': 'Novartis Pharmaceuticals', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Novartis Pharmaceuticals'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Novartis Pharmaceuticals', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}