Ignite Creation Date:
2025-12-24 @ 11:37 PM
Ignite Modification Date:
2025-12-25 @ 9:27 PM
Study NCT ID:
NCT01220856
Status:
COMPLETED
Last Update Posted:
2021-03-11
First Post:
2010-10-07
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Reparixin in Pancreatic Islet Transplantation
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003922', 'term': 'Diabetes Mellitus, Type 1'}], 'ancestors': [{'id': 'D003920', 'term': 'Diabetes Mellitus'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C490707', 'term': 'reparixin'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'daffonchio@dompe.it', 'phone': '+39 583831', 'title': 'Luisa Daffonchio, PhD', 'organization': 'Dompé SpA'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': 'Through study completion, till follow-up (up to 1 year after the second islet infusion).', 'eventGroups': [{'id': 'EG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosoppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression', 'otherNumAtRisk': 6, 'deathsNumAtRisk': 6, 'otherNumAffected': 6, 'seriousNumAtRisk': 6, 'deathsNumAffected': 0, 'seriousNumAffected': 3}, {'id': 'EG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant. Rapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.', 'otherNumAtRisk': 3, 'deathsNumAtRisk': 3, 'otherNumAffected': 3, 'seriousNumAtRisk': 3, 'deathsNumAffected': 0, 'seriousNumAffected': 1}], 'otherEvents': [{'term': 'Anaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Hypothyroidism', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Endocrine disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Abdominal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 5, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 5, 'numAffected': 5}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Stomatitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Infusion site pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Oedema', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Hepatic haemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Hepatobiliary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Blood bicarbonate decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Blood creatinine increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Body temperature increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'C-reactive protein increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Fibrin degradation product increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Hypocalcaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Hypokalaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Musculoskeletal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Neuralgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Acne', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Erythema', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 6, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Rash', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 2, 'numAffected': 1}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Hypertension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Hypotension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}], 'seriousEvents': [{'term': 'Anemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Gastrointestinal hemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Peritoneal hemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Drug administration error', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Diabetic ketoacidosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Renal impairment', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Renal and urinary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}, {'term': 'Hemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 6, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 3, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 13.0'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'The Percentage of Insulin-independent Patients Following Single Infusion Islet Cell Transplantation at Day 75 +/- 5', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'day 75 +/- 5 post-transplant', 'description': 'Insulin-independence was defined as freedom from the need to take exogenous insulin for 14 or more consecutive days, with adequate glycemic control, as defined by:\n\n* HbA1c level of less than 7%;\n* glucose level after an overnight fast not exceeding 140 mg/dL (7.8 mmol/L) more than 3 times a week (based on measuring capillary glucose level a minimum of 7 times in a 7-day period);\n* glucose level not exceeding 2-hour postprandial levels of 180 mg/dL (10 mmol/L) more than 4 times a week (based on measuring capillary glucose level a minimum of 21 times in a 7-day period).', 'unitOfMeasure': 'percentage of patients', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population: All patients who were randomized and received the transplant were included in the efficacy population.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'The Percentage of Insulin-independent Patients Following Islet Cell Transplantation up to One Year After the Last Transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'title': 'transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '50', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'up to one year after the transplant', 'description': 'Insulin-independence was defined as freedom from the need to take exogenous insulin for 14 or more consecutive days, with adequate glycemic control, as defined by:\n\n* HbA1c level of less than 7%;\n* glucose level after an overnight fast not exceeding 140 mg/dL (7.8 mmol/L) more than 3 times a week (based on measuring capillary glucose level a minimum of 7 times in a 7-day period);\n* glucose level not exceeding 2-hour postprandial levels of 180 mg/dL (10 mmol/L) more than 4 times a week (based on measuring capillary glucose level a minimum of 21 times in a 7-day period).', 'unitOfMeasure': 'percentage of patients', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population: All patients who were randomized and received the transplant were included in the efficacy population.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Time to Achieve Insulin-independence After the Transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'categories': [{'measurements': [{'value': '66.3', 'spread': '73.7', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'up to 1 year after transplant 2', 'description': 'Time to achieve insulin-independence after the transplant was defined as the number of days between islet infusion and onset of insulin-independence. This was calculated as: date of onset of insulin-independence minus the islet infusion date.', 'unitOfMeasure': 'days', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population: All patients who were randomized and received the transplant were included in the efficacy population'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Total Time of Insulin Independence After the Transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant. Rapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'categories': [{'measurements': [{'value': '276.0', 'spread': '96.2', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'up to 1 year after transplant 2', 'description': 'Total time of insulin-independence after the transplant. This was defined as the number of days between the onset and loss of insulin-independence and was calculated as the date of loss of insulin-independence minus the date of onset of insulin-independence.\n\nOf the 3 patients who achieve insulin-independence after transplant 2, only 2 remained insulin-independent up to 1 year and the mean (SD) total time of insulin-independence after the second transplant was 276 (96.2) days with a range between 208 and 344 days.', 'unitOfMeasure': 'total number of days', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population: All patients who were randomized and received the transplant were included in the efficacy population.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Absolute Change in Average Daily Insulin Requirements From Pre-transplant Levels', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'title': 'Month 1 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-0.3', 'spread': '0.3', 'groupId': 'OG000'}, {'value': '0.1', 'spread': '0.1', 'groupId': 'OG001'}]}]}, {'title': 'Month 3 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-0.3', 'spread': '0.2', 'groupId': 'OG000'}]}]}, {'title': 'Month 6 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-0.2', 'spread': '0.0', 'groupId': 'OG000'}]}]}, {'title': 'Month 1 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-0.6', 'spread': '0.2', 'groupId': 'OG000'}]}]}, {'title': 'Month 3 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-0.6', 'spread': '0.3', 'groupId': 'OG000'}]}]}, {'title': 'Month 6 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-0.5', 'spread': '0.4', 'groupId': 'OG000'}]}]}, {'title': 'Month 12 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-0.7', 'spread': '0.4', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Months 1, 3, 6, 12 post-transplant', 'description': 'Daily insulin requirement was calculated as the average requirement over the previous week (seven days).', 'unitOfMeasure': 'IU/kg/day', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population: All patients who were randomized and received the transplant were included in the efficacy population'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Percentage Change in Average Daily Insulin Requirements From Pre-transplant Levels', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'title': 'Month 1 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-41.9', 'spread': '39.9', 'groupId': 'OG000'}, {'value': '16.4', 'spread': '20.2', 'groupId': 'OG001'}]}]}, {'title': 'Month 3 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-50.3', 'spread': '24.4', 'groupId': 'OG000'}]}]}, {'title': 'Month 6 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-32.0', 'spread': '8.9', 'groupId': 'OG000'}]}]}, {'title': 'Month 1 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-90.8', 'spread': '11.3', 'groupId': 'OG000'}]}]}, {'title': 'Month 3 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-88.7', 'spread': '17.8', 'groupId': 'OG000'}]}]}, {'title': 'Month 6 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-81.8', 'spread': '36.5', 'groupId': 'OG000'}]}]}, {'title': 'Month 12 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-100.0', 'spread': '0.0', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Months 1, 3, 6, 12 post-transplant', 'description': 'Daily insulin requirement was calculated as the average requirement over the previous week (seven days).', 'unitOfMeasure': 'Percentage change', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population: All patients who were randomized and received the transplant were included in the efficacy population'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Absolute Change in Fasted HbA1c From Pre-transplant Levels', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'title': 'Month 1 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-1.53', 'spread': '0.49', 'groupId': 'OG000'}, {'value': '-0.87', 'spread': '0.40', 'groupId': 'OG001'}]}]}, {'title': 'Month 3 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-2.90', 'spread': '0.74', 'groupId': 'OG000'}]}]}, {'title': 'Month 6 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-1.87', 'spread': '0.60', 'groupId': 'OG000'}]}]}, {'title': 'Month 1 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-3.15', 'spread': '0.57', 'groupId': 'OG000'}]}]}, {'title': 'Month 3 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-3.10', 'spread': '0.76', 'groupId': 'OG000'}]}]}, {'title': 'Month 6 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-3.05', 'spread': '1.03', 'groupId': 'OG000'}]}]}, {'title': 'Month 12 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-3.65', 'spread': '0.92', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Months 1, 3, 6, 12 post-transplant', 'description': 'The absolute change between the time-point value and baseline value.', 'unitOfMeasure': 'Percentage of Hb', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population: All patients who were randomized and received the transplant were included in the efficacy population'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Percentage Change in Fasted HbA1c From Pre-transplant Levels', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein.\n\nInvestigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice.\n\nMaintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'title': 'Month 1 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-16.7', 'spread': '4.5', 'groupId': 'OG000'}, {'value': '-11.2', 'spread': '5.4', 'groupId': 'OG001'}]}]}, {'title': 'Month 3 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-30.3', 'spread': '7.9', 'groupId': 'OG000'}]}]}, {'title': 'Month 6 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-19.7', 'spread': '7.2', 'groupId': 'OG000'}]}]}, {'title': 'Month 1 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-32.8', 'spread': '5.9', 'groupId': 'OG000'}]}]}, {'title': 'Month 3 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-32.2', 'spread': '7.4', 'groupId': 'OG000'}]}]}, {'title': 'Month 6 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-31.6', 'spread': '10.1', 'groupId': 'OG000'}]}]}, {'title': 'Month 12 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-37.4', 'spread': '9.2', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Months 1, 3, 6, 12 post-transplant', 'description': 'The absolute percentage between the time-point value and baseline value.', 'unitOfMeasure': 'Percentage change', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population: All patients who were randomized and received the transplant were included in the efficacy population'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'The Percentage of Patients Free of Hypoglycaemic Events With Reduced Awareness', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'title': 'month 1 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '100', 'groupId': 'OG000'}, {'value': '100', 'groupId': 'OG001'}]}]}, {'title': 'month 3 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '100', 'groupId': 'OG000'}]}]}, {'title': 'month 6 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '100', 'groupId': 'OG000'}]}]}, {'title': 'month 1 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '100', 'groupId': 'OG000'}]}]}, {'title': 'month 3 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '100', 'groupId': 'OG000'}]}]}, {'title': 'month 6 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '100', 'groupId': 'OG000'}]}]}, {'title': 'month 12 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '100', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Months 1, 3, 6, 12 post-transplant', 'description': 'Reduced awareness is defined as a reduced ability to recognize symptoms of hypoglycemia, sometimes referred to as "hypoglycemia unawareness".', 'unitOfMeasure': 'Percentage of patients', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population: All patients who were randomized and received the transplant were included in the efficacy population'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Number of Participants With Adverse Events by Severity and With Serious Adverse Events', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'title': 'TEAE mild', 'categories': [{'measurements': [{'value': '5', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'TEAE moderate', 'categories': [{'measurements': [{'value': '6', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}, {'title': 'TEAE severe', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'SAE', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'up to 1 year after transplant', 'description': 'Safety was assessed by monitoring the incidence and severity of adverse events (AEs) and serious AEs (SAEs) throughout the study up to 1 year after last transplant.\n\nA serious adverse event is an adverse reaction that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a birth defect.', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety Population: all patients who were randomized into the study.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'AUC (-10 to 120 Minutes Post-dose) of Glucose Derived From Mixed Meal Tolerance Test (MMTT) at 1, 3, 6 and 12 Months Post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'title': 'Month 1, transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '318.9', 'spread': '155.1', 'groupId': 'OG000'}, {'value': '308.3', 'spread': '105.4', 'groupId': 'OG001'}]}]}, {'title': 'Month 3, transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '235.0', 'spread': '77.6', 'groupId': 'OG000'}]}]}, {'title': 'Month 6, transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '277.2', 'spread': '59.9', 'groupId': 'OG000'}]}]}, {'title': 'Month 1, transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '162.5', 'spread': '36.3', 'groupId': 'OG000'}]}]}, {'title': 'Month 3, transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '171.2', 'spread': '58.1', 'groupId': 'OG000'}]}]}, {'title': 'Month 6, transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '184.1', 'spread': '74.4', 'groupId': 'OG000'}]}]}, {'title': 'Month 12, last transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '123.7', 'spread': '18.3', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '-10 to 120 Minutes Post-dose at Months 1, 3, 6, 12 post-transplant', 'description': 'Glucose level reflects the metabolic control. The MMTT was performed after an overnight fast, at baseline (within 1 week prior to randomization), and at each of the following timepoints.\n\nAUC was calculated using the trapezoidal rule.', 'unitOfMeasure': 'mg*hr/dL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population: All patients who were randomized and received the transplant were included in the efficacy population.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'AUC (-10 to 120 Minutes Post-dose) of C-peptide Derived From Mixed Meal Tolerance Test (MMTT) at 1, 3, 6 and 12 Months Post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'title': 'Month 1 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '0.951', 'spread': '0.875', 'groupId': 'OG000'}, {'value': '0.200', 'spread': '0.000', 'groupId': 'OG001'}]}]}, {'title': 'Month 3 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '1.789', 'spread': '1.059', 'groupId': 'OG000'}]}]}, {'title': 'Month 6 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '1.426', 'spread': '1.114', 'groupId': 'OG000'}]}]}, {'title': 'Month 1 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '3.302', 'spread': '1.661', 'groupId': 'OG000'}]}]}, {'title': 'Month 3 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '2.488', 'spread': '2.038', 'groupId': 'OG000'}]}]}, {'title': 'Month 6 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '2.531', 'spread': '1.831', 'groupId': 'OG000'}]}]}, {'title': 'Month 12 (last transplant)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '4.042', 'spread': '1.683', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '-10 to 120 Minutes Post-dose at Months 1, 3, 6, 12 post-transplant', 'description': 'C-peptide level is an indirect measure of pancreatic beta-cell function. The MMTT was performed after an overnight fast, at baseline (within 1 week prior to randomization), and at each of the following timepoints.\n\nAUC was calculated using the trapezoidal rule.', 'unitOfMeasure': 'mg*hr/dL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population: All patients who were randomized and received the transplant were included in the efficacy population.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'AUC (-10 to 120 Minutes Post-dose) of Insulin Derived From Mixed Meal Tolerance Test (MMTT) at 1, 3, 6 and 12 Months Post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'title': 'Month 1 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '19.08', 'spread': '15.72', 'groupId': 'OG000'}, {'value': '7.58', 'spread': '2.91', 'groupId': 'OG001'}]}]}, {'title': 'Month 3 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '28.25', 'spread': '33.43', 'groupId': 'OG000'}]}]}, {'title': 'Month 6 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '13.41', 'spread': '7.81', 'groupId': 'OG000'}]}]}, {'title': 'Month 1 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '20.99', 'spread': '11.89', 'groupId': 'OG000'}]}]}, {'title': 'Month 3 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '22.85', 'spread': '23.07', 'groupId': 'OG000'}]}]}, {'title': 'Month 6 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '19.97', 'spread': '16.40', 'groupId': 'OG000'}]}]}, {'title': 'Month 12 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '36.04', 'spread': '13.83', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '-10 to 120 Minutes Post-dose at Months 1, 3, 6, 12 post-transplant', 'description': 'Insulin level is a direct measure of pancreatic beta-cell function. The MMTT was performed after an overnight fast, at baseline (within 1 week prior to randomization), and at each of the following timepoints.\n\nAUC was calculated using the trapezoidal rule.', 'unitOfMeasure': 'μU*hr/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population: All patients who were randomized and received the transplant were included in the efficacy population. This population was based on the treatment randomized, regardless of the treatment actually received.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'AUC(-10 to 120 Min Post Dose)/IEQ/kg for C Peptide Derived From Mixed Meal Tolerance Test (MMTT) at 1, 3, 6 Months Post-transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'title': 'Month 1 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '0.193', 'spread': '0.158', 'groupId': 'OG000'}, {'value': '0.044', 'spread': '0.004', 'groupId': 'OG001'}]}]}, {'title': 'Month 3 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '0.366', 'spread': '0.158', 'groupId': 'OG000'}]}]}, {'title': 'Month 6 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '0.341', 'spread': '0.265', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': '-10 to 120 Minutes Post-dose at Months 1, 3, 6, 12 post-transplant', 'description': 'For Transplant 1 (patients on reparixin), the mean C-Peptide AUC (derived from the MMTT) corrected by IEQ/kg values were calculated.\n\nAUC was calculated using the trapezoidal rule and normalized by the actual number of islet equivalents (IEQ) per kilo infused (IEQ/kg).', 'unitOfMeasure': '(mg*hr/dL)/IEQ/kg', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population: All patients who were randomized and received the transplant were included in the efficacy population. This population was based on the treatment randomized, regardless of the treatment actually received.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'The Percentage of Patients Free of Severe Hypoglycaemic Events', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'title': 'month 1 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '100', 'groupId': 'OG000'}, {'value': '100', 'groupId': 'OG001'}]}]}, {'title': 'month 3 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '100', 'groupId': 'OG000'}]}]}, {'title': 'month 6 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '100', 'groupId': 'OG000'}]}]}, {'title': 'month 1 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '100', 'groupId': 'OG000'}]}]}, {'title': 'month 3 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '100', 'groupId': 'OG000'}]}]}, {'title': 'month 6 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '100', 'groupId': 'OG000'}]}]}, {'title': 'month 12 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '100', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'Months 1, 3, 6, 12 post-transplant', 'description': 'A severe hypoglycemic event is defined as an event with one of the following symptoms: "memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness, or visual symptoms", in which the subject was unable to treat him/herself and which was associated with either a blood glucose level \\<54mg/dL or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration.', 'unitOfMeasure': 'Percentage of patients', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population: All patients who were randomized and received the transplant were included in the efficacy population.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Beta-cell Function as Assessed by Beta-score', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'title': 'Month 1, transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '1.83', 'spread': '1.17', 'groupId': 'OG000'}, {'value': '1.33', 'spread': '1.53', 'groupId': 'OG001'}]}]}, {'title': 'Month 3, transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '3.75', 'spread': '1.26', 'groupId': 'OG000'}]}]}, {'title': 'Month 6, transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '1.67', 'spread': '1.53', 'groupId': 'OG000'}]}]}, {'title': 'Month 1, transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '5.25', 'spread': '1.50', 'groupId': 'OG000'}]}]}, {'title': 'Month 3, transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '4.75', 'spread': '1.89', 'groupId': 'OG000'}]}]}, {'title': 'Month 6, transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '4.75', 'spread': '2.63', 'groupId': 'OG000'}]}]}, {'title': 'Month 12, transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '6.50', 'spread': '0.71', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Months 1, 3, 6, 12 post-transplant', 'description': 'The beta-score provides a simple clinical scoring system that encompasses glycemic control, diabetes therapy, and endogenous insulin secretion that correlates well with physiological measures of beta-cell function. On this basis, it is suitable as an overall measure of beta-cell transplant function.\n\nBeta score is a composite scoring system based on fasting plasma glucose values, HbA1c, insulin independence or use of insulin/OHAs, and the determination of stimulated C-peptide levels. Normal values are given a score of 2, intermediate values merit a score of 1, and clearly abnormal values garner no points. Thus, a perfect score is 8, and a score of 0 indicates absolute absence of beta-cell function.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population: All patients who were randomized and received the transplant were included in the efficacy population.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Beta-cell Function as Assessed by TEF/IEQ/kg Ratio', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'title': 'Month 1 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '111.9', 'spread': '64.1', 'groupId': 'OG000'}, {'value': '13.6', 'spread': '49.6', 'groupId': 'OG001'}]}]}, {'title': 'Month 3 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '176.6', 'spread': '105.0', 'groupId': 'OG000'}]}]}, {'title': 'Month 6 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '121.1', 'spread': '30.0', 'groupId': 'OG000'}]}]}, {'title': 'Month 1 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '1.143', 'spread': '0.278', 'groupId': 'OG000'}]}]}, {'title': 'Month 3 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '1.133', 'spread': '0.336', 'groupId': 'OG000'}]}]}, {'title': 'Month 6 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '1.100', 'spread': '0.407', 'groupId': 'OG000'}]}]}, {'title': 'Month 12 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '1.320', 'spread': '0.212', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'At months 1, 3, 6 after transplant 1 and months 1,3, 6, and 12 after transplant 2', 'description': 'The TEF/IEQ/kg ratio is a parameter to assess transplant efficiency corrected by the number of transplanted islets.', 'unitOfMeasure': 'ratio', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Efficacy Population: All patients who were randomized and received the transplant were included in the efficacy population. This population was based on the treatment randomized, regardless of the treatment actually received.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Serum Level of Alanine Amino Transferase (ALT)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'title': 'Pre-transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '23.0', 'spread': '9.0', 'groupId': 'OG000'}, {'value': '28.7', 'spread': '22.9', 'groupId': 'OG001'}]}]}, {'title': 'Day 1 post-transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '27.5', 'spread': '8.7', 'groupId': 'OG000'}, {'value': '24.7', 'spread': '18.6', 'groupId': 'OG001'}]}]}, {'title': 'Day 2 post-transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '26.3', 'spread': '9.3', 'groupId': 'OG000'}, {'value': '36.3', 'spread': '29.7', 'groupId': 'OG001'}]}]}, {'title': 'Day 3 post-transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '29.7', 'spread': '9.7', 'groupId': 'OG000'}, {'value': '46.3', 'spread': '34.9', 'groupId': 'OG001'}]}]}, {'title': 'Day 4 post-transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '38.5', 'spread': '9.0', 'groupId': 'OG000'}, {'value': '64.7', 'spread': '23.0', 'groupId': 'OG001'}]}]}, {'title': 'Day 5 post-transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '63.7', 'spread': '21.9', 'groupId': 'OG000'}, {'value': '98.0', 'spread': '33.2', 'groupId': 'OG001'}]}]}, {'title': 'Day 6 post-transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '86.0', 'spread': '34.0', 'groupId': 'OG000'}, {'value': '108.3', 'spread': '34.4', 'groupId': 'OG001'}]}]}, {'title': 'Day 7 post-transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '114.6', 'spread': '56.4', 'groupId': 'OG000'}, {'value': '108.3', 'spread': '45.7', 'groupId': 'OG001'}]}]}, {'title': 'Month 1 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '25.8', 'spread': '7.7', 'groupId': 'OG000'}, {'value': '29.7', 'spread': '28.9', 'groupId': 'OG001'}]}]}, {'title': 'Month 3 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '25.0', 'spread': '8.7', 'groupId': 'OG000'}]}]}, {'title': 'Pre-transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '18.5', 'spread': '7.9', 'groupId': 'OG000'}]}]}, {'title': 'Day 1 post-transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '24.8', 'spread': '10.8', 'groupId': 'OG000'}]}]}, {'title': 'Day 2 post-transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '22.8', 'spread': '9.3', 'groupId': 'OG000'}]}]}, {'title': 'Day 3 post-transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '22.8', 'spread': '7.5', 'groupId': 'OG000'}]}]}, {'title': 'Day 4 post-transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '28.8', 'spread': '10.8', 'groupId': 'OG000'}]}]}, {'title': 'Day 5 post-transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '31.8', 'spread': '11.7', 'groupId': 'OG000'}]}]}, {'title': 'Day 6 post-transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '31.8', 'spread': '13.0', 'groupId': 'OG000'}]}]}, {'title': 'Day 7 post-transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '35.3', 'spread': '12.1', 'groupId': 'OG000'}]}]}, {'title': 'Month 1 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '28.0', 'spread': '12.5', 'groupId': 'OG000'}]}]}, {'title': 'Month 3 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '21.0', 'spread': '3.6', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Pre-transplant and at days 1-7 and months 1 and 3 post-transplant', 'description': 'ALT is commonly measured clinically as part of liver function tests.', 'unitOfMeasure': 'U/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety population: all patients who were randomized into the study.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Serum Level of Aspartate Amino Transferase (AST)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein.\n\nInvestigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'title': 'Pre-transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '22.3', 'spread': '14.6', 'groupId': 'OG000'}, {'value': '20.0', 'spread': '7.5', 'groupId': 'OG001'}]}]}, {'title': 'Day 1 post-transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '30.5', 'spread': '12.1', 'groupId': 'OG000'}, {'value': '18.7', 'spread': '7.4', 'groupId': 'OG001'}]}]}, {'title': 'Day 2 post-transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '22.3', 'spread': '9.2', 'groupId': 'OG000'}, {'value': '27.3', 'spread': '12.5', 'groupId': 'OG001'}]}]}, {'title': 'Day 3 post-transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '24.7', 'spread': '12.8', 'groupId': 'OG000'}, {'value': '31.7', 'spread': '13.4', 'groupId': 'OG001'}]}]}, {'title': 'Day 4 post-transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '31.8', 'spread': '9.3', 'groupId': 'OG000'}, {'value': '49.0', 'spread': '35.5', 'groupId': 'OG001'}]}]}, {'title': 'Day 5 post-transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '60.2', 'spread': '28.7', 'groupId': 'OG000'}, {'value': '74.3', 'spread': '26.6', 'groupId': 'OG001'}]}]}, {'title': 'Day 6 post-transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '64.2', 'spread': '22.1', 'groupId': 'OG000'}, {'value': '64.3', 'spread': '29.4', 'groupId': 'OG001'}]}]}, {'title': 'Day 7 post-transplant 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '82.0', 'spread': '43.4', 'groupId': 'OG000'}, {'value': '55.0', 'spread': '29.7', 'groupId': 'OG001'}]}]}, {'title': 'Month 1 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '15.5', 'spread': '3.6', 'groupId': 'OG000'}, {'value': '17.7', 'spread': '10.0', 'groupId': 'OG001'}]}]}, {'title': 'Month 3 (transplant 1)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '15.8', 'spread': '5.0', 'groupId': 'OG000'}]}]}, {'title': 'Pre-transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '17.0', 'spread': '6.2', 'groupId': 'OG000'}]}]}, {'title': 'Day 1 post-transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '33.0', 'spread': '18.7', 'groupId': 'OG000'}]}]}, {'title': 'Day 2 post-transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '21.0', 'spread': '7.0', 'groupId': 'OG000'}]}]}, {'title': 'Day 3 post-transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '21.5', 'spread': '5.8', 'groupId': 'OG000'}]}]}, {'title': 'Day 4 post-transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '26.8', 'spread': '9.7', 'groupId': 'OG000'}]}]}, {'title': 'Day 5 post-transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '28.5', 'spread': '7.5', 'groupId': 'OG000'}]}]}, {'title': 'Day 6 post-transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '23.0', 'spread': '8.8', 'groupId': 'OG000'}]}]}, {'title': 'Day 7 post-transplant 2', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '25.3', 'spread': '10.4', 'groupId': 'OG000'}]}]}, {'title': 'Month 1 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '4', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '17.3', 'spread': '3.3', 'groupId': 'OG000'}]}]}, {'title': 'Month 3 (transplant 2)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '13.7', 'spread': '5.0', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Pre-transplant and at days 1-7 and months 1 and 3 post-transplant', 'description': 'AST is commonly measured clinically as part of liver function tests.', 'unitOfMeasure': 'U/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety population: all patients who were randomized into the study.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Change From Pre-transplant in Cytokine Levels - CXCL8', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein.\n\nInvestigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'title': '6 hours post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '11.0', 'spread': '14.4', 'groupId': 'OG000'}, {'value': '22.1', 'spread': '19.0', 'groupId': 'OG001'}]}]}, {'title': '12 hours post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '43.8', 'spread': '45.5', 'groupId': 'OG000'}, {'value': '32.9', 'spread': '43.3', 'groupId': 'OG001'}]}]}, {'title': '24 hours post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '10.6', 'spread': '21.8', 'groupId': 'OG000'}, {'value': '11.3', 'spread': '2.1', 'groupId': 'OG001'}]}]}, {'title': '72 hours post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '17.3', 'spread': '12.0', 'groupId': 'OG000'}, {'value': '2.6', 'spread': '8.5', 'groupId': 'OG001'}]}]}, {'title': '120 hours post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '1.2', 'spread': '8.0', 'groupId': 'OG000'}, {'value': '-2.2', 'spread': '5.4', 'groupId': 'OG001'}]}]}, {'title': '168 hours post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-6.8', 'spread': '5.0', 'groupId': 'OG000'}, {'value': '-2.8', 'spread': '1.7', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': '6, 12, 24, 72, 120, and 168 hours post-transplant 1', 'description': 'Time course of inflammatory chemokines/cytokines as assessed by serum levels of CXCL8 (CXC ligand 8 \\[formerly interleukin (IL)-8\\]) (time frame: 0, 6, 12, 24, 72, 120, and 168 hours after islet infusion).', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety population: all patients who were randomized into the study.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Change From Pre-transplant in Cytokine Levels - CXCL1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein.\n\nInvestigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'title': '6 hours post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-12.5', 'spread': '51.8', 'groupId': 'OG000'}, {'value': '-31.9', 'spread': '31.0', 'groupId': 'OG001'}]}]}, {'title': '12 hours post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '11.8', 'spread': '72.4', 'groupId': 'OG000'}, {'value': '-16.8', 'spread': '16.2', 'groupId': 'OG001'}]}]}, {'title': '24 hours post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '1.4', 'spread': '61.9', 'groupId': 'OG000'}, {'value': '-65.6', 'spread': '127.0', 'groupId': 'OG001'}]}]}, {'title': '72 hours post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '63.7', 'spread': '40.7', 'groupId': 'OG000'}, {'value': '-51.9', 'spread': '157.7', 'groupId': 'OG001'}]}]}, {'title': '120 hours post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '8.7', 'spread': '16.1', 'groupId': 'OG000'}, {'value': '-60.2', 'spread': '130.6', 'groupId': 'OG001'}]}]}, {'title': '168 hours post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-10.7', 'spread': '65.0', 'groupId': 'OG000'}, {'value': '-16.3', 'spread': '88.7', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': '6, 12, 24, 72, 120, and 168 hours post-transplant 1', 'description': 'Time course of inflammatory chemokines/cytokines as assessed by serum levels of CXCL1 (time frame: 0, 6, 12, 24, 72, 120, and 168 hours after islet infusion).', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety population: all patients who were randomized into the study.'}, {'type': 'OTHER_PRE_SPECIFIED', 'title': 'Change From Pre-transplant in Cytokine Levels - IL-6', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein.\n\nInvestigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'OG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant.\n\nRapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'classes': [{'title': '6 hours post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '0.5', 'spread': '4.0', 'groupId': 'OG000'}, {'value': '12.1', 'spread': '10.6', 'groupId': 'OG001'}]}]}, {'title': '12 hours post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '15.5', 'spread': '20.6', 'groupId': 'OG000'}, {'value': '23.4', 'spread': '27.9', 'groupId': 'OG001'}]}]}, {'title': '24 hours post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '7.6', 'spread': '10.7', 'groupId': 'OG000'}, {'value': '2.3', 'spread': '7.5', 'groupId': 'OG001'}]}]}, {'title': '72 hours post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '16.3', 'spread': '13.5', 'groupId': 'OG000'}, {'value': '3.1', 'spread': '13.3', 'groupId': 'OG001'}]}]}, {'title': '120 hours post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '0.8', 'spread': '5.2', 'groupId': 'OG000'}, {'value': '-5.6', 'spread': '14.1', 'groupId': 'OG001'}]}]}, {'title': '168 hours post-transplant', 'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'categories': [{'measurements': [{'value': '-2.6', 'spread': '3.2', 'groupId': 'OG000'}, {'value': '-5.5', 'spread': '8.6', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': '6, 12, 24, 72, 120, and 168 hours post-transplant 1', 'description': 'Time course of inflammatory chemokines/cytokines as assessed by serum levels of interleukin 6 (IL-6) (time frame: 0, 6, 12, 24, 72, 120, and 168 hours after islet infusion).', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety population: all patients who were randomized into the study.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosuppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'FG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant. Rapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '6'}, {'groupId': 'FG001', 'numSubjects': '3'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '4'}, {'groupId': 'FG001', 'numSubjects': '3'}]}], 'dropWithdraws': [{'type': 'graft loss', 'reasons': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '3'}]}, {'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'A total of 9 patients were enrolled into the study; 6 were randomized to reparixin and 3 to the control group. All in the control group and 2 in the reparixin group were withdrawn after Transplant 1 due to graft loss. 4 in the reparixin group received Transplant 2. Thereafter, 1 was withdrawn due to graft loss. 1 was lost to follow-up.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '6', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosoppression regimen see the other arm description.\n\nReparixin: Reparixin + immunosuppression'}, {'id': 'BG001', 'title': 'No Experimental Intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant. Rapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '46.2', 'spread': '8.8', 'groupId': 'BG000'}, {'value': '48.0', 'spread': '7.0', 'groupId': 'BG001'}, {'value': '46.8', 'spread': '7.9', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '5', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Italy', 'categories': [{'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}], 'populationDescription': 'Safety Population: All patients who were randomized into the study were included in the safety population.'}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 9}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2010-07-28', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2021-02', 'completionDateStruct': {'date': '2013-04-30', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2021-02-18', 'studyFirstSubmitDate': '2010-10-07', 'resultsFirstSubmitDate': '2021-01-07', 'studyFirstSubmitQcDate': '2010-10-13', 'lastUpdatePostDateStruct': {'date': '2021-03-11', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2021-02-18', 'studyFirstPostDateStruct': {'date': '2010-10-14', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2021-03-11', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2013-04-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'The Percentage of Insulin-independent Patients Following Islet Cell Transplantation up to One Year After the Last Transplant', 'timeFrame': 'up to one year after the transplant', 'description': 'Insulin-independence was defined as freedom from the need to take exogenous insulin for 14 or more consecutive days, with adequate glycemic control, as defined by:\n\n* HbA1c level of less than 7%;\n* glucose level after an overnight fast not exceeding 140 mg/dL (7.8 mmol/L) more than 3 times a week (based on measuring capillary glucose level a minimum of 7 times in a 7-day period);\n* glucose level not exceeding 2-hour postprandial levels of 180 mg/dL (10 mmol/L) more than 4 times a week (based on measuring capillary glucose level a minimum of 21 times in a 7-day period).'}, {'measure': 'Time to Achieve Insulin-independence After the Transplant 2', 'timeFrame': 'up to 1 year after transplant 2', 'description': 'Time to achieve insulin-independence after the transplant was defined as the number of days between islet infusion and onset of insulin-independence. This was calculated as: date of onset of insulin-independence minus the islet infusion date.'}, {'measure': 'Total Time of Insulin Independence After the Transplant', 'timeFrame': 'up to 1 year after transplant 2', 'description': 'Total time of insulin-independence after the transplant. This was defined as the number of days between the onset and loss of insulin-independence and was calculated as the date of loss of insulin-independence minus the date of onset of insulin-independence.\n\nOf the 3 patients who achieve insulin-independence after transplant 2, only 2 remained insulin-independent up to 1 year and the mean (SD) total time of insulin-independence after the second transplant was 276 (96.2) days with a range between 208 and 344 days.'}, {'measure': 'Absolute Change in Average Daily Insulin Requirements From Pre-transplant Levels', 'timeFrame': 'Months 1, 3, 6, 12 post-transplant', 'description': 'Daily insulin requirement was calculated as the average requirement over the previous week (seven days).'}, {'measure': 'Percentage Change in Average Daily Insulin Requirements From Pre-transplant Levels', 'timeFrame': 'Months 1, 3, 6, 12 post-transplant', 'description': 'Daily insulin requirement was calculated as the average requirement over the previous week (seven days).'}, {'measure': 'Absolute Change in Fasted HbA1c From Pre-transplant Levels', 'timeFrame': 'Months 1, 3, 6, 12 post-transplant', 'description': 'The absolute change between the time-point value and baseline value.'}, {'measure': 'Percentage Change in Fasted HbA1c From Pre-transplant Levels', 'timeFrame': 'Months 1, 3, 6, 12 post-transplant', 'description': 'The absolute percentage between the time-point value and baseline value.'}, {'measure': 'The Percentage of Patients Free of Hypoglycaemic Events With Reduced Awareness', 'timeFrame': 'Months 1, 3, 6, 12 post-transplant', 'description': 'Reduced awareness is defined as a reduced ability to recognize symptoms of hypoglycemia, sometimes referred to as "hypoglycemia unawareness".'}, {'measure': 'Number of Participants With Adverse Events by Severity and With Serious Adverse Events', 'timeFrame': 'up to 1 year after transplant', 'description': 'Safety was assessed by monitoring the incidence and severity of adverse events (AEs) and serious AEs (SAEs) throughout the study up to 1 year after last transplant.\n\nA serious adverse event is an adverse reaction that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a birth defect.'}, {'measure': 'AUC (-10 to 120 Minutes Post-dose) of Glucose Derived From Mixed Meal Tolerance Test (MMTT) at 1, 3, 6 and 12 Months Post-transplant', 'timeFrame': '-10 to 120 Minutes Post-dose at Months 1, 3, 6, 12 post-transplant', 'description': 'Glucose level reflects the metabolic control. The MMTT was performed after an overnight fast, at baseline (within 1 week prior to randomization), and at each of the following timepoints.\n\nAUC was calculated using the trapezoidal rule.'}, {'measure': 'AUC (-10 to 120 Minutes Post-dose) of C-peptide Derived From Mixed Meal Tolerance Test (MMTT) at 1, 3, 6 and 12 Months Post-transplant', 'timeFrame': '-10 to 120 Minutes Post-dose at Months 1, 3, 6, 12 post-transplant', 'description': 'C-peptide level is an indirect measure of pancreatic beta-cell function. The MMTT was performed after an overnight fast, at baseline (within 1 week prior to randomization), and at each of the following timepoints.\n\nAUC was calculated using the trapezoidal rule.'}, {'measure': 'AUC (-10 to 120 Minutes Post-dose) of Insulin Derived From Mixed Meal Tolerance Test (MMTT) at 1, 3, 6 and 12 Months Post-transplant', 'timeFrame': '-10 to 120 Minutes Post-dose at Months 1, 3, 6, 12 post-transplant', 'description': 'Insulin level is a direct measure of pancreatic beta-cell function. The MMTT was performed after an overnight fast, at baseline (within 1 week prior to randomization), and at each of the following timepoints.\n\nAUC was calculated using the trapezoidal rule.'}, {'measure': 'AUC(-10 to 120 Min Post Dose)/IEQ/kg for C Peptide Derived From Mixed Meal Tolerance Test (MMTT) at 1, 3, 6 Months Post-transplant 1', 'timeFrame': '-10 to 120 Minutes Post-dose at Months 1, 3, 6, 12 post-transplant', 'description': 'For Transplant 1 (patients on reparixin), the mean C-Peptide AUC (derived from the MMTT) corrected by IEQ/kg values were calculated.\n\nAUC was calculated using the trapezoidal rule and normalized by the actual number of islet equivalents (IEQ) per kilo infused (IEQ/kg).'}, {'measure': 'The Percentage of Patients Free of Severe Hypoglycaemic Events', 'timeFrame': 'Months 1, 3, 6, 12 post-transplant', 'description': 'A severe hypoglycemic event is defined as an event with one of the following symptoms: "memory loss, confusion, uncontrollable behavior, irrational behavior, unusual difficulty in awakening, suspected seizure, seizure, loss of consciousness, or visual symptoms", in which the subject was unable to treat him/herself and which was associated with either a blood glucose level \\<54mg/dL or prompt recovery after oral carbohydrate, i.v. glucose, or glucagon administration.'}, {'measure': 'Beta-cell Function as Assessed by Beta-score', 'timeFrame': 'Months 1, 3, 6, 12 post-transplant', 'description': 'The beta-score provides a simple clinical scoring system that encompasses glycemic control, diabetes therapy, and endogenous insulin secretion that correlates well with physiological measures of beta-cell function. On this basis, it is suitable as an overall measure of beta-cell transplant function.\n\nBeta score is a composite scoring system based on fasting plasma glucose values, HbA1c, insulin independence or use of insulin/OHAs, and the determination of stimulated C-peptide levels. Normal values are given a score of 2, intermediate values merit a score of 1, and clearly abnormal values garner no points. Thus, a perfect score is 8, and a score of 0 indicates absolute absence of beta-cell function.'}, {'measure': 'Beta-cell Function as Assessed by TEF/IEQ/kg Ratio', 'timeFrame': 'At months 1, 3, 6 after transplant 1 and months 1,3, 6, and 12 after transplant 2', 'description': 'The TEF/IEQ/kg ratio is a parameter to assess transplant efficiency corrected by the number of transplanted islets.'}, {'measure': 'Serum Level of Alanine Amino Transferase (ALT)', 'timeFrame': 'Pre-transplant and at days 1-7 and months 1 and 3 post-transplant', 'description': 'ALT is commonly measured clinically as part of liver function tests.'}, {'measure': 'Serum Level of Aspartate Amino Transferase (AST)', 'timeFrame': 'Pre-transplant and at days 1-7 and months 1 and 3 post-transplant', 'description': 'AST is commonly measured clinically as part of liver function tests.'}, {'measure': 'Change From Pre-transplant in Cytokine Levels - CXCL8', 'timeFrame': '6, 12, 24, 72, 120, and 168 hours post-transplant 1', 'description': 'Time course of inflammatory chemokines/cytokines as assessed by serum levels of CXCL8 (CXC ligand 8 \\[formerly interleukin (IL)-8\\]) (time frame: 0, 6, 12, 24, 72, 120, and 168 hours after islet infusion).'}, {'measure': 'Change From Pre-transplant in Cytokine Levels - CXCL1', 'timeFrame': '6, 12, 24, 72, 120, and 168 hours post-transplant 1', 'description': 'Time course of inflammatory chemokines/cytokines as assessed by serum levels of CXCL1 (time frame: 0, 6, 12, 24, 72, 120, and 168 hours after islet infusion).'}, {'measure': 'Change From Pre-transplant in Cytokine Levels - IL-6', 'timeFrame': '6, 12, 24, 72, 120, and 168 hours post-transplant 1', 'description': 'Time course of inflammatory chemokines/cytokines as assessed by serum levels of interleukin 6 (IL-6) (time frame: 0, 6, 12, 24, 72, 120, and 168 hours after islet infusion).'}], 'primaryOutcomes': [{'measure': 'The Percentage of Insulin-independent Patients Following Single Infusion Islet Cell Transplantation at Day 75 +/- 5', 'timeFrame': 'day 75 +/- 5 post-transplant', 'description': 'Insulin-independence was defined as freedom from the need to take exogenous insulin for 14 or more consecutive days, with adequate glycemic control, as defined by:\n\n* HbA1c level of less than 7%;\n* glucose level after an overnight fast not exceeding 140 mg/dL (7.8 mmol/L) more than 3 times a week (based on measuring capillary glucose level a minimum of 7 times in a 7-day period);\n* glucose level not exceeding 2-hour postprandial levels of 180 mg/dL (10 mmol/L) more than 4 times a week (based on measuring capillary glucose level a minimum of 21 times in a 7-day period).'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Islet transplantation', 'Type 1 diabetes mellitus'], 'conditions': ['Pancreatic Islet Transplantation in Type 1 Diabetes Mellitus']}, 'referencesModule': {'references': [{'pmid': '39735417', 'type': 'DERIVED', 'citation': 'Ajmal N, Bogart MC, Khan P, Max-Harry IM, Healy AM, Nunemaker CS. Identifying Promising Immunomodulators for Type 1 Diabetes (T1D) and Islet Transplantation. J Diabetes Res. 2024 Dec 20;2024:5151171. doi: 10.1155/jdr/5151171. eCollection 2024.'}, {'pmid': '23912763', 'type': 'DERIVED', 'citation': 'Citro A, Cantarelli E, Piemonti L. Anti-inflammatory strategies to enhance islet engraftment and survival. Curr Diab Rep. 2013 Oct;13(5):733-44. doi: 10.1007/s11892-013-0401-0.'}]}, 'descriptionModule': {'briefSummary': 'Inhibition of CXCL8 activity might represent a relevant therapeutic target to prevent injury occurring after pancreatic islet transplantation. Reparixin is a novel and specific inhibitor of CXCL8. This study is designed to explore the efficacy of reparixin in preventing graft dysfunction after islet transplantation in type 1 diabetes patients (T1D).', 'detailedDescription': 'Pancreatic islet transplantation has become a feasible option in the treatment of T1D which offers advantages over whole pancreas transplantation. However to date insulin independence can be obtained in most cases only after the patient has received repeated infusions from several donors. A non-specific immune response, mediated predominantly by innate inflammatory processes, coupled with specific cellular immune responses, possibly promoted by early inflammation, play a major role in the loss of transplanted islets from the liver. PMNs have been found to be the predominant cell types infiltrating in vitro the islets. In this regard, CXCL8 has been shown to be expressed by human islets and could play a crucial role in triggering the inflammatory reaction. Thus, CXCL8 might represent a relevant therapeutic target to prevent early graft failure. The efficacy of reparixin in improving graft outcome in mice models of intrahepatic islet transplantation, as well as the safety shown in human phase 1 and 2 studies, provide a rationale for a clinical study aimed at evaluating the effect of reparixin in preventing graft dysfunction after islet transplantation in T1D patients.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion criteria:\n\n* Ages 18-65 years, inclusive.\n* Patients eligible for pancreatic islet transplantation based on local accepted practice and guidelines. This includes at least: a)clinical history compatible with T1D with insulin-dependence for \\>5 years; b) undetectable stimulated (arginine or MMTT) C-peptide levels (\\<0.3 ng/mL) in the 12 months before transplant. Sites will comply with any additional or more stringent criteria locally accepted, as per centre practice.\n* Patients with adequate renal reserve as per calculated creatinine clearance (CLcr) \\> 60 mL/min according to the Cockcroft-Gault formula (1976).\n* Planned intrahepatic islet transplantation alone from a non-living donor with brain death.\n* Planned infusion of 4000 to 7000 islet equivalent (IEQ)/kg body weight.\n* Patients willing and able to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations.\n* Patients given written informed consent, prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.\n\nExclusion criteria:\n\n* Recipients of any previous transplant, except from recipients of a previous pancreatic islet transplantation that has failed, are off immunosuppression since at least 1 year and have negative anti-HLA.\n* Recipients of islet from a non-heart beating donor.\n* A body mass index \\>30 kg/m2 or patient weight \\<45 kg.\n* Pre-transplant average daily insulin requirement \\>1 IU/kg/day.\n* Pre-transplant HbA1c \\>11%.\n* Patients with hepatic dysfunction as defined by increased ALT/AST \\> 3 x ULN and increased total bilirubin \\> 3mg/dL \\[\\>51.3 micromol/L\\]).\n* Patients who receive treatment for a medical condition requiring chronic use of systemic steroids.\n* Treatment with any anti-diabetic medication other than insulin within 4 weeks of transplant.\n* Use of any investigational agent within 4 weeks of enrolment.\n* Hypersensitivity to:\n\n * ibuprofen or to more than one non steroidal anti-inflammatory drug\n * medications belonging to the class of sulfonamides, such as sulfamethazine, sulfamethoxazole, sulfasalazine, nimesulide or celecoxib.\n* Pregnant or breast-feeding women; unwillingness to use effective contraceptive measures (females and males).\n\nSites will comply with any additional exclusion criteria locally accepted, as per centre practice.'}, 'identificationModule': {'nctId': 'NCT01220856', 'briefTitle': 'Reparixin in Pancreatic Islet Transplantation', 'organization': {'class': 'INDUSTRY', 'fullName': 'Dompé Farmaceutici S.p.A'}, 'officialTitle': 'A Phase 2 Multicenter, Randomized, Open Label, Parallel Assignment, Pilot Study to Assess the Efficacy and Safety of Reparixin Following Islet Transplantation in Patients With Type 1 Diabetes Mellitus', 'orgStudyIdInfo': {'id': 'REP0110'}, 'secondaryIdInfos': [{'id': '2010-019424-31', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Reparixin', 'description': 'Reparixin + Immunosuppression\n\nReparixin was administered at a dose of 2.772 mg/kg body weight/hour for 7 days (168 hours) at each transplant. It was administered as a continuous IV infusion into a (high-flow) central vein. Investigational Product infusion was to begin approximately 12 hours (range between 6 to 16 hours) before each pancreatic islet infusion was started. The Investigator identified the time to start study drug administration.\n\nReparixin was given to all patients of this arm using the same dosing solution (reparixin 11.00 mg/mL), but the pump rate was adjusted to provide an infusion rate of approximately 0.25 mL/kg/hour.\n\nFor immunosoppression regimen see the other arm description.', 'interventionNames': ['Drug: Reparixin']}, {'type': 'NO_INTERVENTION', 'label': 'No experimental intervention', 'description': 'Immunosuppression only. Induction: First islet infusion: anti-thymocyte globulin (ATG), administered IV (central vein) at the dose of 1.5 mg/kg on Day -1, 0, 1, and 2 of islet infusion. The first ATG injection was preceded by a bolus IV injection of 500 mg methylprednisolone. Induction for the second islet infusion was to be administered per center practice. Maintenance: Mycophenolate mofetil (MMF), administered orally at the dose of 1 g twice a day, starting on Day -1 of the first islet infusion; Tacrolimus, administered orally starting on Day -1 of the first islet infusion at a dose of 0.087 mg/kg twice a day. Thereafter, dosing was to be targeted to blood trough levels of 8 to 10 ng/mL. Administration continued up to Month 3 after the first transplant. Rapamycin was to replace tacrolimus from Month 3 after the first transplant. It was to be administered orally at the starting dose of 0.1 mg/kg once a day, then targeted to a blood trough level of 10 to 12 ng/mL.'}], 'interventions': [{'name': 'Reparixin', 'type': 'DRUG', 'otherNames': ['REP'], 'description': 'Reparixin + immunosuppression', 'armGroupLabels': ['Reparixin']}]}, 'contactsLocationsModule': {'locations': [{'zip': '01307', 'city': 'Dresden', 'country': 'Germany', 'facility': 'University Hospital Carl Gustav Carus Dresden', 'geoPoint': {'lat': 51.05089, 'lon': 13.73832}}, {'zip': '20132', 'city': 'Milan', 'country': 'Italy', 'facility': 'Ospedale San Raffaele', 'geoPoint': {'lat': 45.46427, 'lon': 9.18951}}], 'overallOfficials': [{'name': 'Lorenzo Piemonti, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Fondazione Centro San Raffaele del Monte Tabor - Milan; Italy'}, {'name': 'Barbara Ludwig, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University Hospital Carl Gustav Carus - Dresden; Germany'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Dompé Farmaceutici S.p.A', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}