Ignite Creation Date:
2025-12-25 @ 2:10 AM
Ignite Modification Date:
2026-03-04 @ 9:55 PM
Study NCT ID:
NCT02743260
Status:
COMPLETED
Last Update Posted:
2019-09-10
First Post:
2016-04-11
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Drug Transporter Interaction Study PHENTRA_2015_KPUK
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'C108475', 'term': 'pitavastatin'}, {'id': 'D008687', 'term': 'Metformin'}, {'id': 'D004077', 'term': 'Digoxin'}, {'id': 'C053001', 'term': 'adefovir'}, {'id': 'C106812', 'term': 'adefovir dipivoxil'}, {'id': 'D000068900', 'term': 'Sitagliptin Phosphate'}], 'ancestors': [{'id': 'D001645', 'term': 'Biguanides'}, {'id': 'D006146', 'term': 'Guanidines'}, {'id': 'D000578', 'term': 'Amidines'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D004071', 'term': 'Digitalis Glycosides'}, {'id': 'D002298', 'term': 'Cardenolides'}, {'id': 'D002301', 'term': 'Cardiac Glycosides'}, {'id': 'D002297', 'term': 'Cardanolides'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D006027', 'term': 'Glycosides'}, {'id': 'D002241', 'term': 'Carbohydrates'}, {'id': 'D014230', 'term': 'Triazoles'}, {'id': 'D001393', 'term': 'Azoles'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D011719', 'term': 'Pyrazines'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 24}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2016-04'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-09', 'completionDateStruct': {'date': '2017-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-09-06', 'studyFirstSubmitDate': '2016-04-11', 'studyFirstSubmitQcDate': '2016-04-13', 'lastUpdatePostDateStruct': {'date': '2019-09-10', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2016-04-19', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2017-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'organic anionic transporter polypeptide 1B1 (OATP1B1): Clearance over bioavailability (CL/F) of pitavastatin', 'timeFrame': '24 hours', 'description': 'PK parameter'}, {'measure': 'organic cation transporters 1 and 2 (OCT1/2), multidrug and toxic compound extrusion transporters 1 and 2,kidney splice variant (MATE1/2K): Renal clearance (CLr) of metformin', 'timeFrame': '24 hours', 'description': 'PK parameter'}, {'measure': 'intestinal p-glycoprotein (P-gp): Peak Plasma Concentration (Cmax) of digoxin', 'timeFrame': '24 hours', 'description': 'PK parameter'}, {'measure': 'renal p-glycoprotein (P-gp): Renal clearance (CLr) of digoxin:', 'timeFrame': '24 hours', 'description': 'PK parameter'}, {'measure': 'organic anion transporter 1 (OAT1): Renal clearance (CLr) of adefovir', 'timeFrame': '24 hours', 'description': 'PK parameter'}, {'measure': 'organic anion transporter 3 (OAT3): Renal clearance (CLr) of sitagliptin', 'timeFrame': '24 hours', 'description': 'PK parameter'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['phenotype', 'transporter', 'cocktail'], 'conditions': ['Healthy']}, 'referencesModule': {'references': [{'pmid': '32719417', 'type': 'DERIVED', 'citation': 'Hsin CH, Stoffel MS, Gazzaz M, Schaeffeler E, Schwab M, Fuhr U, Taubert M. Combinations of common SNPs of the transporter gene ABCB1 influence apparent bioavailability, but not renal elimination of oral digoxin. Sci Rep. 2020 Jul 27;10(1):12457. doi: 10.1038/s41598-020-69326-y.'}, {'pmid': '31247117', 'type': 'DERIVED', 'citation': 'Trueck C, Hsin CH, Scherf-Clavel O, Schaeffeler E, Lenssen R, Gazzaz M, Gersie M, Taubert M, Quasdorff M, Schwab M, Kinzig M, Sorgel F, Stoffel MS, Fuhr U. A Clinical Drug-Drug Interaction Study Assessing a Novel Drug Transporter Phenotyping Cocktail With Adefovir, Sitagliptin, Metformin, Pitavastatin, and Digoxin. Clin Pharmacol Ther. 2019 Dec;106(6):1398-1407. doi: 10.1002/cpt.1564. Epub 2019 Aug 12.'}]}, 'descriptionModule': {'briefSummary': 'The objective of the present study is to contribute to establishing in vivo phenotyping procedures for organic anionic transporter polypeptide 1B1 (OATP1B1), organic cation transporters 1 and 2 (OCT1/2), multidrug and toxic compound extrusion transporters 1 and 2,kidney splice variant (MATE1/2K), organic anion transporters 1 and 3 (OAT1/3), and p-glycoprotein (P-gp) transporters via a cocktail approach. To this end, marker substrates for each of the respective transporters are administered as single doses in one period each and as a cocktail in one period to 24 healthy volunteers, and phenotyping metrics are derived from plasma and urine concentrations.', 'detailedDescription': 'Blood sampling: - 0:15 h pre-dose, 0:15, 0:30, 0:45, 1:00, 1:20, 1:40, 2:00, 2:20, 2:40, 3:00, 3:30, 4:00, 5:00, 6:00, 8:00, 12:00, 16:00, 24:00 hours post-dose\n\nUrine Sampling: Pre-dose, 0-4 hours, 4-8 hours, 8-12 hours, 12-16 hours, 16-24 hours\n\nDrug analysis: by liquid chromatography - tandem mass spectrometry (LC-MS/MS)\n\nPharmacokinetic Characteristics: Evaluation is carried out using standard noncompartmental characteristics including: area under the plasma concentration vs. time curve truncated at time t (AUC0-t), area under the plasma concentration vs. time curve extrapolated to infinity (AUC0-∞), peak plasma concentration (Cmax), time of occurrence of Cmax (tmax), apparent elimination half-life (t½), clearance over bioavailability (CL/F), renal clearance (CLr) and renal secretion. The evaluation may be completed by compartmental population pharmacokinetic approaches.\n\nStatistical evaluation: Pharmacokinetic characteristics are compared for cocktail administration vs. individual administration by standard average bioequivalence assessment.\n\nSafety, tolerability: Adverse events, laboratory and clinical parameters and vital signs will be assessed.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '85 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Caucasian\n* Body mass index (BMI) between and inclusive 18.5 and 30 kg/m2\n* Willing and capable to confirm written consent prior to enrolment after ample information has been provided\n* Normal findings in the medical history unless the principal investigator considers an abnormality to be clinically relevant.\n* Considered to be healthy by the principal investigator on the basis of extensive pre-study screening-\n\nExclusion Criteria:\n\nStandard for healthy volunteers, including:\n\n* Female subjects only: positive results in pregnancy test\n* Female subjects only: lactating women\n* Female subjects only: subjects who do not use or do not agree to use appropriate contraceptive methods during the study as defined in Note for Guidance on Non-Clinical Safety Studies for the Conduct of Human Clinical Trials for Pharmaceuticals (CHMP/ICH/286/95 modification)'}, 'identificationModule': {'nctId': 'NCT02743260', 'briefTitle': 'Drug Transporter Interaction Study PHENTRA_2015_KPUK', 'organization': {'class': 'OTHER', 'fullName': 'University of Cologne'}, 'officialTitle': 'Single Centre in Vivo Cocktail Phenotyping Study on OATP1B1, OCT1/2, MATE1/2K, OAT1/3, and P-gp Drug Transporters in Healthy Volunteers', 'orgStudyIdInfo': {'id': 'PHENTRA_2015_KPUK'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'pitavastatin (OATP1B1)', 'description': '2 mg pitavastatin single dose', 'interventionNames': ['Drug: pitavastatin']}, {'type': 'EXPERIMENTAL', 'label': 'metformin (MATE1, MATE2K, OCT1, OCT2)', 'description': '500 mg metformin single dose', 'interventionNames': ['Drug: Metformin']}, {'type': 'EXPERIMENTAL', 'label': 'digoxin (intestinal & renal P-glycoprotein)', 'description': '0.5 mg digoxin single dose', 'interventionNames': ['Drug: digoxin']}, {'type': 'EXPERIMENTAL', 'label': 'adefovir dipivoxil (OAT1)', 'description': '10 mg adefovir dipivoxil single dose', 'interventionNames': ['Drug: Adefovir']}, {'type': 'EXPERIMENTAL', 'label': 'sitagliptin (OAT3)', 'description': '100 mg sitagliptin single dose', 'interventionNames': ['Drug: sitagliptin']}, {'type': 'EXPERIMENTAL', 'label': 'cocktail (all substances)', 'description': 'combination of all individual drugs at respective single doses', 'interventionNames': ['Drug: pitavastatin', 'Drug: Metformin', 'Drug: digoxin', 'Drug: Adefovir', 'Drug: sitagliptin']}], 'interventions': [{'name': 'pitavastatin', 'type': 'DRUG', 'otherNames': ['Livazo®'], 'armGroupLabels': ['cocktail (all substances)', 'pitavastatin (OATP1B1)']}, {'name': 'Metformin', 'type': 'DRUG', 'otherNames': ['Metformin-CT®'], 'armGroupLabels': ['cocktail (all substances)', 'metformin (MATE1, MATE2K, OCT1, OCT2)']}, {'name': 'digoxin', 'type': 'DRUG', 'otherNames': ['Digacin®'], 'armGroupLabels': ['cocktail (all substances)', 'digoxin (intestinal & renal P-glycoprotein)']}, {'name': 'Adefovir', 'type': 'DRUG', 'otherNames': ['Hepsera®'], 'armGroupLabels': ['adefovir dipivoxil (OAT1)', 'cocktail (all substances)']}, {'name': 'sitagliptin', 'type': 'DRUG', 'otherNames': ['Januvia®'], 'armGroupLabels': ['cocktail (all substances)', 'sitagliptin (OAT3)']}]}, 'contactsLocationsModule': {'locations': [{'zip': '50931', 'city': 'Cologne', 'state': 'North Rhine-Westphalia', 'country': 'Germany', 'facility': 'Department of Pharmacology I, University Hospital Cologne', 'geoPoint': {'lat': 50.93333, 'lon': 6.95}}], 'overallOfficials': [{'name': 'Uwe Fuhr, Prof. Dr.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Department of Pharmacology I, University Hospital Cologne Cologne, NRW, Germany, 50931'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Cologne', 'class': 'OTHER'}, 'collaborators': [{'name': 'Umm Al-Qura University', 'class': 'OTHER'}, {'name': 'Institute for Biomedical and Pharmaceutical Research (IBMP), Nürnberg-Heroldsberg, Germany', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Acting Director, Department of Pharmacology I', 'investigatorFullName': 'Prof. Dr. Uwe Fuhr', 'investigatorAffiliation': 'University of Cologne'}}}}