Ignite Creation Date:
2025-12-25 @ 4:05 AM
Ignite Modification Date:
2026-01-29 @ 3:34 AM
Study NCT ID:
NCT02274402
Status:
COMPLETED
Last Update Posted:
2025-11-20
First Post:
2014-08-25
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Pharmacokinetics of Prednisone in Adults
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D001800', 'term': 'Blood Specimen Collection'}], 'ancestors': [{'id': 'D013048', 'term': 'Specimen Handling'}, {'id': 'D019411', 'term': 'Clinical Laboratory Techniques'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D011677', 'term': 'Punctures'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}, {'id': 'D008919', 'term': 'Investigative Techniques'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Biospecimen Description :\n\n* Standard blood test as planned in the routine care follow up of corticotherapy. Especially, numeration blood formula, renal function estimated by MDRD formula, liver function (transminases, γGT, alkaline phosphatase, bilirubinemia, prothrombin).\n* Albuminemia, transcortin, HbA1c, 8am cortisol.\n* 4 ml of blood in an dry tube for pharmacokinetic studies at each blood sample, precising the delay between the last dose of treatment and th sampling.\n* Buccal cell collection swab'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 114}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-11'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-09', 'completionDateStruct': {'date': '2016-06', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-11-17', 'studyFirstSubmitDate': '2014-08-25', 'studyFirstSubmitQcDate': '2014-10-23', 'lastUpdatePostDateStruct': {'date': '2025-11-20', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2014-10-24', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2015-11', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'composite Pharmacokinetic parameter for Prednisone', 'timeFrame': 'Up to 12 months', 'description': 'assessed by : Bioavailability of prednisone, apparent volume of distribution, apparent clearance, absorption and elimination constants of free prednisolone'}], 'secondaryOutcomes': [{'measure': 'Side effects', 'timeFrame': 'Up to 12 months', 'description': 'bone demineralisation,'}, {'measure': 'Side effects', 'timeFrame': 'Up to 12 months', 'description': 'metabolic complication,'}, {'measure': 'Side effects', 'timeFrame': 'Up to 12 months', 'description': 'infectious complication'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Prednisone', 'Glucocorticoids', 'pharmacokinetics'], 'conditions': ['Patients Receiving Prednisone']}, 'referencesModule': {'references': [{'pmid': '15634032', 'type': 'BACKGROUND', 'citation': 'Czock D, Keller F, Rasche FM, Haussler U. Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet. 2005;44(1):61-98. doi: 10.2165/00003088-200544010-00003.'}, {'pmid': '8513854', 'type': 'BACKGROUND', 'citation': 'Rollin C, Chosidow O, Diquet B, Dutreuil C, Herson S, Revuz J, Delchier JC. Comparative study of availability of prednisolone after intestinal infusion of prednisolone metasulfobenzoate and prednisone. Eur J Clin Pharmacol. 1993;44(4):395-9. doi: 10.1007/BF00316481.'}, {'pmid': '1302763', 'type': 'BACKGROUND', 'citation': 'Wald JA, Law RM, Ludwig EA, Sloan RR, Middleton E Jr, Jusko WJ. Evaluation of dose-related pharmacokinetics and pharmacodynamics of prednisolone in man. J Pharmacokinet Biopharm. 1992 Dec;20(6):567-89. doi: 10.1007/BF01064420.'}, {'pmid': '31625621', 'type': 'RESULT', 'citation': 'Mangin O, Zheng Y, Bouazza N, Foissac F, Benaboud S, Lui G, Hirt D, Mouthon L, Treluyer JM, Urien S. Free prednisolone pharmacokinetics predicted from total concentrations in patients with inflammatory - immunonologic conditions. Fundam Clin Pharmacol. 2020 Apr;34(2):270-278. doi: 10.1111/fcp.12515. Epub 2019 Nov 21.'}]}, 'descriptionModule': {'briefSummary': 'This is a monocentric study, in the Internal Medicine Service of Cochin Hospital, Paris. Our main objective is to determine the pharmacokinetic properties of prednisone, secondary objectives are to determine the covariates affecting the prednisone pharmacokinetics and the relationship between glucocorticoid exposition levels and their side effects. The investigators will use a prospective, observational, population pharmacokinetic approach. 100 patients starting a prednisone treatment \\>7,5mg/d for an expected period \\>3 months will be recruited and followed over 6 months.', 'detailedDescription': 'OBJECTIVES Main objective Describe the pharmacokinetic of prednisone when administered to adult patients in the setting of an internal medicine service.\n\nSecondary objectives To identify individual vulnerability factors (renal and hepatic functions, albuminemia, age, comedications) and glucocorticoid tolerance factors in adults.\n\nTo study the association between individual exposition and glucocorticoids\' frequent and clinically significative side effects.\n\nMETHOD Conduct of research Population follow up Clinical and biological data will be collected through an observational prospective mono-centric study. Patients\' inclusion will be performed in the "Internal medicine service of Cochin hospital, Assistance Publique - Hôpitaux de Paris (AP-HP)" during hospitalization and will be supervised by the pharmacology service of Cochin hospital.\n\nThe evaluated drug is prednisone, used for routine care in auto-immune and other systemic inflammatory diseases. Prednisone will be administered according to the service usual practices, dosing will be determined according to the patient\'s disease. The study will not modify the prescription of the treatment. Blood tests will be performed at different intervals during each patient\'s normal biological monitoring of the treatment.\n\nSeveral tubes will be collected for the needs of the study at the time of each venipuncture (blood sample or peripheral venous catheter laying). The delay between drug intake and blood sampling will be attributed to routine care hazard, samples will be then realized on different occasions. No venous or arterial punction will be specifically planned for protocol purposes, GLUCOMAD\'s samples will be adapted to routine care blood samplings.\n\n1st visit : Patients recruiting phase Will occur during hospitalization. Its goal is to check for eligibility criteria.\n\nDuring this visit, the investigator will explain the patient the purpose of the study. The patient will receive an information notice and a consent form.\n\nPatient\'s data collection :\n\n* Age\n* Sex\n* Pregnancy, menopause\n* Personal history of kidney, liver or thyroid disease. Personal or familial history of adrenal pathology, impaired glucose tolerance, diabetes mellitus, gestational diabetes, high blood pressure, preeclampsia, hypertension in pregnancy, open angle glaucoma, cataract, osteoporosis/osteopenia, osteoporotic fracture, gastric ulcer, psychiatric disorder, dyslipidemia.\n* Osteoporosis risk factors\n* Blood pressure, body weight, height, and clinical exam results looking in particular for hepatocellular insufficiency, or uremic syndrome.\n* Face photography at the beginning and the end of the study participation.\n\nData collection about prednisone :\n\n* Treatment indication\n* Anterior corticotherapy, and optionally, anterior treatment duration, total dose taken up (as estimated by recovered orders from the patients pharmacy), and side effects of this previous treatment.\n* Name of the chosen molecule (international nonproprietary name and commercial name), daily dosing (mg/Kg), treatment\'s start date.\n* Adherence to the treatment, evaluated by the medication possession ratio (MPR42).\n* Clinical symptoms of corticotherapy side effects Actual co-occuring treatments,\n* Especially for medications interacting with P450 cytochrome, or P glycoprotein. Including the non proprietary name, treatment\'s start date, dosage, and optionally the results of plasma rates testing.\n* Side effects treatments : anti hypertensive drugs, hypolipidemic drugs, potassium supplementation, oral antidiabetic drugs/insulin, psychotropic drugs.\n\nBlood tests Follow up\n\n* During hospitalizations, routine care blood samples will be performed, on these occasions, blood will be collected in a dry tube for the study purposes.\n* At the end of the attack phase, albumin, transcortin, HbA1c, and 8am cortisol will be assayed.\n* Usual clinical and biological follow up results, including body weight and side effects monitoring, will be collected.\n* Medication possession ratio assessment\n* Co-occuring treatments Collection Sampling procedure, place of collection Blood samples necessary to the study will be stored in an anonymous way. Anonymity will be guaranteed all the study long.\n\nStorage location and conditions Samples for non pharmacological tests will be tested and destroyed. All the pharmacological samples will be stored during the study at -80°C in the pharmacology service of Cochin hospital where pharmacological analyses will be performed.\n\nSamples processing Molecules plasma assays will be performed in the drug dosing platform of clinical pharmacology service of Cochin hospital, AP-HP. Free and bound forms of prednisolone will be tested.\n\nSamples management Pharmacological samples will be stored at the end of the study for complementary studies.\n\nStatistical considerations Statistical analyses We propose to describe prednisone\'s pharmacokinetic in adults thanks to a population pharmacokinetic approach. This technique is specially adapted for populations affected by rare inflammatory diseases that are supported in internal medicine services. Indeed, it only requires a few measures in each patient and allows flexibility in data collection ; thus it enables us to assay concentrations on routine care samples. This method will allow us to describe an average subject pharmacokinetic and then to estimate interindividual variability in the population under prednisone treatment. We will the attempt to explain this variability according to covariates as age, bodyweight, size, liver or kidney insufficiency, or co-occurring treatments.\n\nIndividual pharmacokinetic parameters will be estimated from this population model through a Bayesian estimation method. Potential associations between individual expositions (i.e. residual concentration, area under the curve, maximal concentration), and prednisone side effects will be studied.\n\nPharmaco-statistical analysis will be made thanks to non linear mixed effects modelisation softwares (Monolix 4.2 or Nonmem 7) to calculate prednisone\'s pharmacokinetic parameters as well as inter-individual variability parameters on one hand and residual variability on the other hand (the latter including intra-individual variability and measurement error).\n\nThe final model will be validated by a simulation technique. Briefly, 500 simulations of the final model will be generated from the original database. Then the 5th, 50th, and 95th percentiles of the simulated predictions will be compared to observations (the simulation median has to be close to the observation\'s median, and 90% of the observation must be between the 5th and 95th percentiles of simulations).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Adults receiving glucocorticoids (Prednisone) are recruited in Service de medicine interne, Hôpital Cochin, Paris', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* receiving Prednisone\n* recruited in Service de Medecine Interne, Cochin hospital, Paris\n* blood sample collected at least one time during his/her follow-up\n\nExclusion Criteria:\n\n* refusal\n* hypersensitivity to prednisone or one of its excipients\n* inability to take a blood sample'}, 'identificationModule': {'nctId': 'NCT02274402', 'acronym': 'Glucomad', 'briefTitle': 'Pharmacokinetics of Prednisone in Adults', 'organization': {'class': 'OTHER', 'fullName': 'Assistance Publique - Hôpitaux de Paris'}, 'officialTitle': 'Study of Pharmacokinetic and Pharmacodynamic Variability of Prednisone, in Adults', 'orgStudyIdInfo': {'id': '2014-A00926-41'}}, 'armsInterventionsModule': {'armGroups': [{'label': 'adults with glucocorticoids', 'description': 'Adults receiving Prednisone', 'interventionNames': ['Biological: blood sampling']}], 'interventions': [{'name': 'blood sampling', 'type': 'BIOLOGICAL', 'description': 'Blood sample of 4 ml at enrolment and then at two following visits', 'armGroupLabels': ['adults with glucocorticoids']}]}, 'contactsLocationsModule': {'locations': [{'zip': '75015', 'city': 'Paris', 'country': 'France', 'facility': 'AP-HP Cochin', 'geoPoint': {'lat': 48.85341, 'lon': 2.3488}}], 'overallOfficials': [{'name': 'Jean-Marc Treluyer, M.D., PhD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Assistance Publique - Hôpitaux de Paris'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Assistance Publique - Hôpitaux de Paris', 'class': 'OTHER'}, 'collaborators': [{'name': 'URC-CIC Paris Descartes Necker Cochin', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}