Ignite Creation Date:
2025-12-24 @ 11:29 PM
Ignite Modification Date:
2025-12-25 @ 9:16 PM
Study NCT ID:
NCT00282256
Status:
COMPLETED
Last Update Posted:
2013-10-17
First Post:
2006-01-24
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
A Study of a Modified-Release Tacrolimus Based Immunosuppression Regimen in Stable Pediatric Liver Transplant Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D016559', 'term': 'Tacrolimus'}], 'ancestors': [{'id': 'D018942', 'term': 'Macrolides'}, {'id': 'D007783', 'term': 'Lactones'}, {'id': 'D009930', 'term': 'Organic Chemicals'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'ClinicalTrials.Disclosure@us.astellas.com', 'title': 'Vice President, Therapeutic Area Head, Transplantation', 'organization': 'Astellas Pharma Global Development, Inc.'}, 'certainAgreement': {'otherDetails': "Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data or until 18 months have elapsed following study completion. Sponsor must receive a site's manuscript at least 30 days prior to publication to ensure that no confidential information of Sponsor is included in the document.", 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}, 'limitationsAndCaveats': {'description': 'Company makes no warranties or representations of any kind as to the posting, expressed or implied, including warranties of merchantability and fitness for a particular purpose, and shall not be liable for any damages.'}}, 'adverseEventsModule': {'timeFrame': 'From the first dose of tacrolimus MR through the last dose day plus 10 days (approximately 54 months).', 'description': 'Adverse events are reported for the modified safety analysis set defined as all participants who took at least 1 dose of tacrolimus and one dose of tacrolimus MR during the pharmacokinetic period of the study.', 'eventGroups': [{'id': 'EG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.', 'otherNumAtRisk': 18, 'otherNumAffected': 11, 'seriousNumAtRisk': 18, 'seriousNumAffected': 6}], 'otherEvents': [{'term': 'Pneumonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 2}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Sinusitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 2}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Tinea capitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 2}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Viral upper respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 2}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Bronchitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Cat scratch disease', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Ear infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Epstein-barr virus infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Escherichia urinary tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Gastroenteritis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Herpes simplex', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Influenza', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Otitis media', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Pharyngitis streptococcal', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Upper respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Urinary tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Urinary tract infection staphylococcal', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Viral infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Alanine aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 2}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Aspartate aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 2}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Blood triglycerides increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Hepatic enzyme increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Low density lipoprotein increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Weight increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 2}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Tremor', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Pyrexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Hyperbilirubinaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Hepatobiliary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Contusion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Glucose tolerance impaired', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Glomerulosclerosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Maxillary sinusitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Urticaria', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Hypertension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Renal impairment', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}], 'seriousEvents': [{'term': 'Bacteraemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Pneumonia mycoplasmal', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Pneumonia streptococcal', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Urinary tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Abdominal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Gastroenteritis eosinophilic', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Cholangitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Hepatobiliary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Liver function test abnormal', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Back pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}, {'term': 'Neck pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 18, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA (6.1)'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'classes': [{'title': 'Day 7: Tacrolimus', 'categories': [{'measurements': [{'value': '198.2', 'spread': '99.2', 'groupId': 'OG000'}]}]}, {'title': 'Day 14: Tacrolimus MR', 'categories': [{'measurements': [{'value': '193.0', 'spread': '78.0', 'groupId': 'OG000'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Ratio of means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '100.9', 'ciLowerLimit': '90.8', 'ciUpperLimit': '112.1', 'estimateComment': 'Tacrolimus/tacrolimus MR ratio of natural log transformed means expressed as a percent.', 'groupDescription': 'The method of analysis of variance was used for the comparisons of AUC0-24. Exposure at steady state was used for tacrolimus (defined as Day 7) and for tacrolimus MR (defined as Day 14). The natural log (ln) was used to transform AUC0-24 prior to analysis and the results were transformed back to the original scale for the presentation of results.', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE', 'testedNonInferiority': True, 'nonInferiorityComment': 'If the 90% CI for AUC0-24 was found to lie entirely within the 80% to 125% range, then the exposure between the two formulations was considered to be equivalent.'}], 'paramType': 'MEAN', 'timeFrame': 'For tacrolimus, Day 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Day 14 at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.', 'description': 'The area under the concentration-time curve was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state using the linear trapezoidal rule. The AUC0-24 for tacrolimus was calculated as the sum of the AUC0-12 and AUC 12-24 for the morning and afternoon doses.', 'unitOfMeasure': 'ng*hr/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'The pharmacokinetic evaluable set was defined as all patients who completed both pharmacokinetic profiles: one for tacrolimus, and one for tacrolimus MR. A complete pharmacokinetic profile was considered to be a profile that was adequate to determine AUC0-24, Cmax, and Cmin.'}, {'type': 'SECONDARY', 'title': 'Maximum Observed Concentration of Tacrolimus (Cmax)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'classes': [{'title': 'Day 7: Tacrolimus', 'categories': [{'measurements': [{'value': '20.7', 'spread': '13.3', 'groupId': 'OG000'}]}]}, {'title': 'Day 14: Tacrolimus MR', 'categories': [{'measurements': [{'value': '15.2', 'spread': '5.7', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'For tacrolimus, Day 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Day 14 at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.', 'description': 'The maximum concentration was calculated from whole blood tacrolimus concentrations for both the tacrolimus and tacrolimus MR at steady state, without interpolation.', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic evaluable set.'}, {'type': 'PRIMARY', 'title': 'Minimum Observed Concentration of Tacrolimus (Cmin)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'classes': [{'title': 'Day 7: Tacrolimus', 'categories': [{'measurements': [{'value': '5.9', 'spread': '2.9', 'groupId': 'OG000'}]}]}, {'title': 'Day 14: Tacrolimus MR', 'categories': [{'measurements': [{'value': '5.3', 'spread': '2.6', 'groupId': 'OG000'}]}]}], 'analyses': [{'groupIds': ['OG000'], 'paramType': 'Ratio of means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '91.8', 'ciLowerLimit': '82.6', 'ciUpperLimit': '102.2', 'estimateComment': 'Tacrolimus/tacrolimus MR ratio of natural log transformed means expressed as a percent.', 'groupDescription': 'The method of analysis of variance was used for the comparisons of Cmin. Exposure at steady state was used for tacrolimus (defined as Day 7) and for tacrolimus MR (defined as Day 14). The natural log (ln) was used to transform Cmin prior to analysis and the results were transformed back to the original scale for the presentation of results.', 'nonInferiorityType': 'NON_INFERIORITY_OR_EQUIVALENCE', 'testedNonInferiority': True, 'nonInferiorityComment': 'If the 90% CI for Cmin was found to lie entirely within the 80% to 125% range, then the exposure between the two formulations was considered to be equivalent.'}], 'paramType': 'MEAN', 'timeFrame': 'Day 7 at 12 hours post-dose (tacrolimus) and Day 14 at 24 hours post-dose (tacrolimus MR).', 'description': 'The trough (minimum) concentration of tacrolimus determined from the tacrolimus whole blood concentration value at the 12 hour post-dose concentration based on the evening dose (i.e., the 8 am concentration) for tacrolimus and the 24-hour time point post-dose for tacrolimus MR, prior to receiving the next dose.', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic evaluable set.'}, {'type': 'PRIMARY', 'title': 'Patient Survival', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '94.44', 'groupId': 'OG000', 'lowerLimit': '83.86', 'upperLimit': '100.00'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'Patient survival was defined as any participant known to be alive at the end of the study.', 'unitOfMeasure': 'percentage of participants', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'The Modified Full Analysis Set included all patients who took at least 1 dose of tacrolimus MR formulation during the extended treatment period.'}, {'type': 'PRIMARY', 'title': 'Graft Survival', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '94.44', 'groupId': 'OG000', 'lowerLimit': '83.86', 'upperLimit': '100.00'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'Graft survival was defined as any participant who did not meet the definition of graft loss, where graft loss was defined as graft failure (re-transplant) or participant death.', 'unitOfMeasure': 'percentage of participants', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified full analysis set.'}, {'type': 'SECONDARY', 'title': 'Time to Maximum Observed Concentration of Tacrolimus (Tmax)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'classes': [{'title': 'Day 7: Tacrolimus', 'categories': [{'measurements': [{'value': '1.0', 'groupId': 'OG000', 'lowerLimit': '0.5', 'upperLimit': '19.7'}]}]}, {'title': 'Day 14: Tacrolimus MR', 'categories': [{'measurements': [{'value': '2.0', 'groupId': 'OG000', 'lowerLimit': '0.9', 'upperLimit': '6.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'For tacrolimus, Day 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Day 14 at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.', 'description': 'Time to reach the first observed maximum concentration of tacrolimus was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state, without interpolation.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic evaluable set.'}, {'type': 'SECONDARY', 'title': 'Percentage of Participants With Biopsy-confirmed Acute Rejection', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '16.67', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'Biopsy-confirmed acute rejection (BCAR) is defined as an episode of acute liver allograft rejection that was confirmed by biopsy results and was Banff grade ≥ I. Biopsies were graded by the pathologist at the clinical site according to the 1997 Banff criteria for grading of acute liver allograft rejection: Indeterminate: Portal inflammatory infiltrate that fails to meet the criteria for diagnosis of acute rejection; Grade I (Mild): Rejection infiltrate in a minority of the triads that is generally mild and confined within the portal spaces; Grade II (Moderate): Rejection infiltrate, expanding to most or all of the triads; Grade III (Severe): Rejection infiltrate, expanding to most or all of the triads, with spillover into periportal areas and moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular hepatocyte. necrosis', 'unitOfMeasure': 'percentage of participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified full analysis set.'}, {'type': 'SECONDARY', 'title': 'Time to Event for Patient Non-survival', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '1204.00', 'groupId': 'OG000', 'lowerLimit': '1204.0', 'upperLimit': '1204.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'For participants who died on study, the median number of days from first dose of study drug to death due to any cause.', 'unitOfMeasure': 'days', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants in the modified full analysis set who died on study.'}, {'type': 'SECONDARY', 'title': 'Time to Event for Graft Non-survival', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '1203.00', 'groupId': 'OG000', 'lowerLimit': '1203.0', 'upperLimit': '1203.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'For participants with graft loss, the median number of days from the first dose of study drug to graft loss. Graft loss was defined as graft failure (re-transplant) or participant death.', 'unitOfMeasure': 'days', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants in the modified full analysis set with graft loss.'}, {'type': 'SECONDARY', 'title': 'Time to First Biopsy-confirmed Acute Rejection', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '748.00', 'groupId': 'OG000', 'lowerLimit': '729.0', 'upperLimit': '773.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'For participants with a biopsy-confirmed acute rejection (BCAR), the median number of days from the first dose of study drug to the date of biopsy confirmation. BCAR is defined as an episode of acute liver allograft rejection that was confirmed by biopsy results and was Banff grade ≥ I. Biopsies were graded by the clinical site pathologist according to the 1997 Banff criteria for grading acute liver allograft rejection: Indeterminate: Portal inflammatory infiltrate that fails to meet the criteria for diagnosis of acute rejection; Grade I: Rejection infiltrate in a minority of the triads that is generally mild and confined within the portal spaces; Grade II: Rejection infiltrate, expanding to most or all of the triads; Grade III: Rejection infiltrate, expanding to most or all of the triads, with spillover into periportal areas and moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular hepatocyte necrosis.', 'unitOfMeasure': 'days', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants in the modified full analysis set with a biopsy-confirmed acute rejection.'}, {'type': 'SECONDARY', 'title': 'Grade of Biopsy-confirmed Acute Rejection Episodes', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'classes': [{'title': 'Grade I', 'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}]}]}, {'title': 'Grade II', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}, {'title': 'Grade III', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'Biopsy-confirmed acute rejection (BCAR) is defined as an episode of acute liver allograft rejection that was confirmed by biopsy results and was Banff grade ≥ I. Biopsies were graded by the clinical site pathologist according to the 1997 Banff criteria for grading of acute liver allograft rejection: Indeterminate: Portal inflammatory infiltrate that fails to meet the criteria for diagnosis of acute rejection; Grade I (Mild): Rejection infiltrate in a minority of the triads that is generally mild and confined within the portal spaces; Grade II (Moderate): Rejection infiltrate, expanding to most or all of the triads; Grade III (Severe): Rejection infiltrate, expanding to most or all of the triads, with spillover into periportal areas and moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular hepatocyte necrosis. For participants with more than one biopsy-confirmed acute rejection episode, the worst case grade is reported.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants in the modified full analysis set with a biopsy-confirmed acute rejection.'}, {'type': 'SECONDARY', 'title': 'Number of Participants Receiving Anti-lymphocyte Antibody Therapy for Acute Rejection', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'Steroid-resistant rejection episodes were treated with anti-lymphocyte antibodies. If a participant had a histologically proven Banff Grade II or III rejection, they could be initiated on anti-lymphocyte antibody treatment per institutional practice.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified full analysis set.'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Multiple Rejection Episodes', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'This analysis includes rejection episodes that were either confirmed by biopsy by the clinical site pathologist or were clinically treated.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified full analysis set.'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Clinically Treated Acute Rejection Episodes', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'classes': [{'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'A clinically treated acute rejection episode was any biopsy-confirmed or suspected rejection episode that was treated with immunosuppressive therapy.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified full analysis set.'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Chronic Rejection', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'Due to the low number of participants with biopsy-confirmed acute rejection episodes, chronic rejection was not analyzed.', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Number of Participants With Treatment Failure', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'Treatment failure was defined as discontinuation of study drug for any reason. Due to discontinuation of the study by the sponsor, treatment failure was not analyzed.', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Primary Reason for Graft Loss', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'classes': [{'title': 'Recurrent disease', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}, {'title': 'Death', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'The primary reason for graft loss was recorded by the Investigator. Graft loss was defined as graft failure (re-transplant) or participant death.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Participants in the modified full analysis set with graft loss.'}, {'type': 'SECONDARY', 'title': 'Safety as Assessed by Clinical Signs and Symptoms, Laboratory Parameters and Diagnostic Tests', 'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'classes': [{'title': 'Any adverse event', 'categories': [{'measurements': [{'value': '12', 'groupId': 'OG000'}]}]}, {'title': 'Any death', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}, {'title': 'Any serious adverse event', 'categories': [{'measurements': [{'value': '6', 'groupId': 'OG000'}]}]}, {'title': 'Any AE leading to a change in study drug dose', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}]}]}, {'title': 'AE leading to study drug discontinuation', 'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'From the first dose of tacrolimus MR formulation through the last dose day plus 10 days (approximately 54 months).', 'description': 'An adverse event (AE) is defined as any reaction, side effect or other untoward medical occurrence, regardless of the relationship to study drug which occurred during the conduct of a clinical study. Clinically significant adverse changes in clinical status, routine laboratory studies or physical examinations were considered adverse events.\n\nA serious adverse event was any adverse event occurring at any dose that resulted in any of the following outcomes:\n\n* Death\n* Life-threatening adverse event\n* Inpatient hospitalization or prolongation of existing hospitalization\n* Persistent or significant disability or incapacity\n* Congenital abnormality or birth defect\n* Important medical event.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified safety analysis set defined as all participants who took at least 1 dose of both tacrolimus and tacrolimus MR formulation during the pharmacokinetic period of the study.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'periods': [{'title': 'Pharmacokinetic Treatment Period', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '19'}]}, {'type': 'Received Tacrolimus', 'achievements': [{'groupId': 'FG000', 'numSubjects': '19'}]}, {'type': 'Received Tacrolimus MR', 'achievements': [{'groupId': 'FG000', 'numSubjects': '18'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '18'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Poor venous access', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}]}, {'title': 'Extension Treatment Period', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '18'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '16'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}]}]}], 'recruitmentDetails': 'Stable liver transplant recipients aged 12 years or younger receiving tacrolimus based immunosuppression regimen.', 'preAssignmentDetails': 'Pharmacokinetic (PK) treatment period was 14 days. Participants who completed the PK period were eligible to continue receiving tacrolimus MR in the extended treatment period, from Day 15 through Month 54.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '18', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.'}], 'measures': [{'title': 'Age Continuous', 'classes': [{'categories': [{'measurements': [{'value': '8.6', 'spread': '2.28', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '13', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '5', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Reason for End Stage Liver Disease', 'classes': [{'title': 'Biliary Atresia', 'categories': [{'measurements': [{'value': '5', 'groupId': 'BG000'}]}]}, {'title': 'Acute Fulminant (Hepatic) Failure', 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}, {'title': 'Fulminant Hepatitis', 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}, {'title': 'Tyrosinemia', 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}, {'title': 'Unknown', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}, {'title': 'Other', 'categories': [{'measurements': [{'value': '6', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Type of Current Transplant', 'classes': [{'title': 'Whole Cadaver', 'categories': [{'measurements': [{'value': '10', 'groupId': 'BG000'}]}]}, {'title': 'Split Cadaver', 'categories': [{'measurements': [{'value': '4', 'groupId': 'BG000'}]}]}, {'title': 'Living Donor', 'categories': [{'measurements': [{'value': '4', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Re-transplant', 'classes': [{'title': 'No', 'categories': [{'measurements': [{'value': '16', 'groupId': 'BG000'}]}]}, {'title': 'Yes', 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}], 'populationDescription': 'The pharmacokinetic evaluable set was defined as all patients who completed both pharmacokinetic profiles: one for tacrolimus, and one for tacrolimus MR.'}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 19}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2004-01'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2013-08', 'dispFirstSubmitDate': '2010-09-22', 'completionDateStruct': {'date': '2008-10', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2013-08-12', 'studyFirstSubmitDate': '2006-01-24', 'dispFirstSubmitQcDate': '2011-11-10', 'resultsFirstSubmitDate': '2013-08-12', 'studyFirstSubmitQcDate': '2006-01-24', 'dispFirstPostDateStruct': {'date': '2011-11-16', 'type': 'ESTIMATED'}, 'lastUpdatePostDateStruct': {'date': '2013-10-17', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2013-08-12', 'studyFirstPostDateStruct': {'date': '2006-01-26', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2013-10-17', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2008-10', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC0-24) for Tacrolimus', 'timeFrame': 'For tacrolimus, Day 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Day 14 at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.', 'description': 'The area under the concentration-time curve was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state using the linear trapezoidal rule. The AUC0-24 for tacrolimus was calculated as the sum of the AUC0-12 and AUC 12-24 for the morning and afternoon doses.'}, {'measure': 'Minimum Observed Concentration of Tacrolimus (Cmin)', 'timeFrame': 'Day 7 at 12 hours post-dose (tacrolimus) and Day 14 at 24 hours post-dose (tacrolimus MR).', 'description': 'The trough (minimum) concentration of tacrolimus determined from the tacrolimus whole blood concentration value at the 12 hour post-dose concentration based on the evening dose (i.e., the 8 am concentration) for tacrolimus and the 24-hour time point post-dose for tacrolimus MR, prior to receiving the next dose.'}, {'measure': 'Patient Survival', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'Patient survival was defined as any participant known to be alive at the end of the study.'}, {'measure': 'Graft Survival', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'Graft survival was defined as any participant who did not meet the definition of graft loss, where graft loss was defined as graft failure (re-transplant) or participant death.'}], 'secondaryOutcomes': [{'measure': 'Maximum Observed Concentration of Tacrolimus (Cmax)', 'timeFrame': 'For tacrolimus, Day 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Day 14 at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.', 'description': 'The maximum concentration was calculated from whole blood tacrolimus concentrations for both the tacrolimus and tacrolimus MR at steady state, without interpolation.'}, {'measure': 'Time to Maximum Observed Concentration of Tacrolimus (Tmax)', 'timeFrame': 'For tacrolimus, Day 7 at 0 (pre-dose), 0.5, 1, 2, 3, 6, 8, 12 (pre-dose), 13, 14, 15, 18, 20, and 24 hours. For tacrolimus MR, Day 14 at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12, 15, 18, 20, and 24 hours post-dose.', 'description': 'Time to reach the first observed maximum concentration of tacrolimus was calculated from whole blood tacrolimus concentrations for both tacrolimus and tacrolimus MR at steady state, without interpolation.'}, {'measure': 'Percentage of Participants With Biopsy-confirmed Acute Rejection', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'Biopsy-confirmed acute rejection (BCAR) is defined as an episode of acute liver allograft rejection that was confirmed by biopsy results and was Banff grade ≥ I. Biopsies were graded by the pathologist at the clinical site according to the 1997 Banff criteria for grading of acute liver allograft rejection: Indeterminate: Portal inflammatory infiltrate that fails to meet the criteria for diagnosis of acute rejection; Grade I (Mild): Rejection infiltrate in a minority of the triads that is generally mild and confined within the portal spaces; Grade II (Moderate): Rejection infiltrate, expanding to most or all of the triads; Grade III (Severe): Rejection infiltrate, expanding to most or all of the triads, with spillover into periportal areas and moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular hepatocyte. necrosis'}, {'measure': 'Time to Event for Patient Non-survival', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'For participants who died on study, the median number of days from first dose of study drug to death due to any cause.'}, {'measure': 'Time to Event for Graft Non-survival', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'For participants with graft loss, the median number of days from the first dose of study drug to graft loss. Graft loss was defined as graft failure (re-transplant) or participant death.'}, {'measure': 'Time to First Biopsy-confirmed Acute Rejection', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'For participants with a biopsy-confirmed acute rejection (BCAR), the median number of days from the first dose of study drug to the date of biopsy confirmation. BCAR is defined as an episode of acute liver allograft rejection that was confirmed by biopsy results and was Banff grade ≥ I. Biopsies were graded by the clinical site pathologist according to the 1997 Banff criteria for grading acute liver allograft rejection: Indeterminate: Portal inflammatory infiltrate that fails to meet the criteria for diagnosis of acute rejection; Grade I: Rejection infiltrate in a minority of the triads that is generally mild and confined within the portal spaces; Grade II: Rejection infiltrate, expanding to most or all of the triads; Grade III: Rejection infiltrate, expanding to most or all of the triads, with spillover into periportal areas and moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular hepatocyte necrosis.'}, {'measure': 'Grade of Biopsy-confirmed Acute Rejection Episodes', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'Biopsy-confirmed acute rejection (BCAR) is defined as an episode of acute liver allograft rejection that was confirmed by biopsy results and was Banff grade ≥ I. Biopsies were graded by the clinical site pathologist according to the 1997 Banff criteria for grading of acute liver allograft rejection: Indeterminate: Portal inflammatory infiltrate that fails to meet the criteria for diagnosis of acute rejection; Grade I (Mild): Rejection infiltrate in a minority of the triads that is generally mild and confined within the portal spaces; Grade II (Moderate): Rejection infiltrate, expanding to most or all of the triads; Grade III (Severe): Rejection infiltrate, expanding to most or all of the triads, with spillover into periportal areas and moderate to severe perivenular inflammation that extends into the hepatic parenchyma and is associated with perivenular hepatocyte necrosis. For participants with more than one biopsy-confirmed acute rejection episode, the worst case grade is reported.'}, {'measure': 'Number of Participants Receiving Anti-lymphocyte Antibody Therapy for Acute Rejection', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'Steroid-resistant rejection episodes were treated with anti-lymphocyte antibodies. If a participant had a histologically proven Banff Grade II or III rejection, they could be initiated on anti-lymphocyte antibody treatment per institutional practice.'}, {'measure': 'Number of Participants With Multiple Rejection Episodes', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'This analysis includes rejection episodes that were either confirmed by biopsy by the clinical site pathologist or were clinically treated.'}, {'measure': 'Number of Participants With Clinically Treated Acute Rejection Episodes', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'A clinically treated acute rejection episode was any biopsy-confirmed or suspected rejection episode that was treated with immunosuppressive therapy.'}, {'measure': 'Number of Participants With Chronic Rejection', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'Due to the low number of participants with biopsy-confirmed acute rejection episodes, chronic rejection was not analyzed.'}, {'measure': 'Number of Participants With Treatment Failure', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'Treatment failure was defined as discontinuation of study drug for any reason. Due to discontinuation of the study by the sponsor, treatment failure was not analyzed.'}, {'measure': 'Primary Reason for Graft Loss', 'timeFrame': 'From enrollment until the end of study (up to 54 months).', 'description': 'The primary reason for graft loss was recorded by the Investigator. Graft loss was defined as graft failure (re-transplant) or participant death.'}, {'measure': 'Safety as Assessed by Clinical Signs and Symptoms, Laboratory Parameters and Diagnostic Tests', 'timeFrame': 'From the first dose of tacrolimus MR formulation through the last dose day plus 10 days (approximately 54 months).', 'description': 'An adverse event (AE) is defined as any reaction, side effect or other untoward medical occurrence, regardless of the relationship to study drug which occurred during the conduct of a clinical study. Clinically significant adverse changes in clinical status, routine laboratory studies or physical examinations were considered adverse events.\n\nA serious adverse event was any adverse event occurring at any dose that resulted in any of the following outcomes:\n\n* Death\n* Life-threatening adverse event\n* Inpatient hospitalization or prolongation of existing hospitalization\n* Persistent or significant disability or incapacity\n* Congenital abnormality or birth defect\n* Important medical event.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Child', 'Pharmacokinetics', 'Immunosuppression Drugs', 'Hepatic transplant', 'Liver Transplantation'], 'conditions': ['Liver Transplantation']}, 'referencesModule': {'references': [{'pmid': '17511684', 'type': 'BACKGROUND', 'citation': 'Heffron TG, Pescovitz MD, Florman S, Kalayoglu M, Emre S, Smallwood G, Wisemandle K, Anania C, Dhadda S, Sawamoto T, Keirns J, Fitzsimmons W, First MR. Once-daily tacrolimus extended-release formulation: 1-year post-conversion in stable pediatric liver transplant recipients. Am J Transplant. 2007 Jun;7(6):1609-15. doi: 10.1111/j.1600-6143.2007.01803.x.'}]}, 'descriptionModule': {'briefSummary': 'A study to assess the pharmacokinetics, safety and effectiveness of tacrolimus in stable pediatric liver transplant patients converted from a Prograf® based immunosuppression regimen to a modified release tacrolimus based immunosuppression regimen.', 'detailedDescription': 'A 1 arm study to assess the pharmacokinetics, and long-term safety and effectiveness of a modified release tacrolimus based immunosuppression regimen in stable pediatric liver transplant patients converted from a Prograf® based immunosuppression regimen.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '12 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Patient is currently receiving Prograf® based immunosuppressive therapy for liver transplantation.\n* Patient has stable whole blood trough level concentrations of Prograf® and is clinically stable\n\nExclusion Criteria:\n\n* Patient has previously received an organ transplant other than a liver\n* Patient is currently receiving sirolimus immunosuppression therapy.'}, 'identificationModule': {'nctId': 'NCT00282256', 'briefTitle': 'A Study of a Modified-Release Tacrolimus Based Immunosuppression Regimen in Stable Pediatric Liver Transplant Patients', 'organization': {'class': 'INDUSTRY', 'fullName': 'Astellas Pharma Inc'}, 'officialTitle': 'A Phase 2, Open-Label, Multi-center Study to Assess the Pharmacokinetics, Long-Term Safety and Tolerability of Tacrolimus in Stable Pediatric Liver Transplant Patients Converted From a Prograf® Based Immunosuppression Regimen to a Modified Release (MR) Tacrolimus Based Immunosuppression Regimen', 'orgStudyIdInfo': {'id': '03-0-160'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Tacrolimus MR', 'description': 'Participants continued to receive their stable twice daily dose of tacrolimus twice daily on Day 1 through Day 7 and on Day 8 were converted to tacrolimus modified release (MR) once-daily in the morning for 7 days on a 1:1 (mg:mg) basis for their total daily dose. Patients who completed the 2-week pharmacokinetic treatment period were eligible to continue receiving tacrolimus MR as part of the extension treatment period of the study. The extended treatment period began on Day 15 and consisted of a single dose of tacrolimus MR once every morning through the end of the study.', 'interventionNames': ['Drug: tacrolimus modified release (MR)', 'Drug: tacrolimus']}], 'interventions': [{'name': 'tacrolimus modified release (MR)', 'type': 'DRUG', 'otherNames': ['Advagraf,', 'FK506E,', 'MR4,', 'FKMR,', 'Astagraf XL'], 'description': 'Oral', 'armGroupLabels': ['Tacrolimus MR']}, {'name': 'tacrolimus', 'type': 'DRUG', 'otherNames': ['Prograf,', 'FK506'], 'description': 'Oral', 'armGroupLabels': ['Tacrolimus MR']}]}, 'contactsLocationsModule': {'locations': [{'zip': '30322', 'city': 'Atlanta', 'state': 'Georgia', 'country': 'United States', 'geoPoint': {'lat': 33.749, 'lon': -84.38798}}, {'zip': '46202', 'city': 'Indianapolis', 'state': 'Indiana', 'country': 'United States', 'geoPoint': {'lat': 39.76838, 'lon': -86.15804}}, {'zip': '70433', 'city': 'New Orleans', 'state': 'Louisiana', 'country': 'United States', 'geoPoint': {'lat': 29.95465, 'lon': -90.07507}}, {'zip': '10029', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '53792', 'city': 'Madison', 'state': 'Wisconsin', 'country': 'United States', 'geoPoint': {'lat': 43.07305, 'lon': -89.40123}}], 'overallOfficials': [{'name': 'Central Contact', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Astellas Pharma US, Inc.'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Astellas Pharma Inc', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}