Study to Ascertain if Prolonged Release Tacrolimus (FK506E - MR4) is Safe and Effective When Used in the Long Term and in Combination With Other Immunosuppressive Drugs in Patients Who Have Received a Transplant
- Conditions
- Heart TransplantationLiver TransplantationKidney Transplantation
- Interventions
- Drug: FK506E
- Registration Number
- NCT02118896
- Lead Sponsor
- Astellas Pharma Europe Ltd.
- Brief Summary
The purpose of this study was to offer patients who had participated in one of the phase II PK or phase III studies on FK506E (MR4) the possibility to continue FK506E (MR4) until commercial availability of the drug and to record long term efficacy and safety data.
- Detailed Description
The objective of this study was to asses the safety and efficacy of FK506E (MR4) as a long-term treatment in transplant recipients. Only patients who had participated in one of the phase II PK or phase III studies on FK506E (MR4) and had received at least one dose of study medication were enrolled.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 850
- Patients who had already participated in the previous phase II pharmacokinetic or phase III studies with FK506E (MR4).
- Patients capable of understanding the purpose and risks of the study, who had been fully informed and given written informed consent to participate in the study.
- Pregnant women or nursing mothers.
- Women unwilling or unable to use adequate contraception during the study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1: FK506E (MR4) FK506E Single open arm of FK506E (MR4). Since this was an extension study for many studies, generally the dose given at enrollment was to be continued. The investigator was permitted to adjust the subject's dose and modify the MR4 dose regimen as deemed necessary to minimize Adverse Events (AEs) and maintain effective immunosuppression. MR4 capsules were taken orally, once daily in the morning. MR4 capsules were to be swallowed with fluid (preferably water) on an empty stomach or at least 1 hour before or 2 to 3 hours after a meal. MR4 was supplied as 0.5 mg, 1 mg and 5 mg capsules in amber glass bottles or in blister packs.
- Primary Outcome Measures
Name Time Method Participant Survival Up to 5.5 years (66 months (phase II) and 24 months (phase III)). Participant survival was analyzed using Kaplan-Meier (KM) method procedures at 66 months (phase 2) and 24 months (phase III). The two-sided 95% confidence intervals (CI) for the estimated rates of patients alive at end of study (EOS) was calculated using Greenwood's formula. Start, event and censor times for the Kaplan-Meier analyses of participant survival were (Event time: day of death, Censor Time: day of last follow-up (for participants prematurely withdrawn from the study), and day of last visit (for participants completing the study) .
Graft Survival Up to 5.5 years ((66 months (phase II) and 30 months (phase III)). Graft survival was analyzed using Kaplan-Meier Method procedures at 66 months (phase II) and 30 months (phase III). The two-sided 95% confidence intervals for the estimated rates of patients free from graft loss at EOS was calculated using Greenwood's formula. Graft loss was defined as re-transplantation or death. For kidney transplantation graft loss was also defined as nephrectomy or return to long-term dialysis. The date of graft loss is the earliest date of either of these events. Start, event and censor times for the Kaplan-Meier analyses of graft survival were (Event time: day of death, Censor Time: day of last follow-up (for participants prematurely withdrawn from the study), and day of last visit (for participants completing the study) .
- Secondary Outcome Measures
Name Time Method Number of Participants With Adverse Events From first dose to duration of participation in the study (up to 6 years and 28 days after EOS). An AE was defined as any untoward medical occurrence in a participant administered study drug, which does not necessarily have a causal relationship with treatment. An AE was, therefore, any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use the study drug, whether or not related to the study drug. Causally-related is defined as a highly probably, probably, possible, not assessable or missing relationship as assessed by the investigator. An SAE was any untoward medical occurrence that at any dose: Resulted in death, was life threatening: did not refer to event which hypothetically might have caused death if more severe); resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect; required inpatient hospitalization/led to prolongation of hospitalization (treatment/observation/examination caused by AE was considered serious); other medically important events.
Biopsy-confirmed Acute Rejection (BCAR) Episodes Up to 6 years. FAS population. Evaluation of biopsy specimens performed by local histopathologist following "Histological Grading of Biopsies for Rejection" using grading relevant to type of organ allograft. Spontaneously resolving AR defined as episode not treated with new/increased corticosteroid medication, antibodies/any other medication and resolved irrespective of any MR4/MMF/azathioprine dose changes; corticosteroid sensitive AR was an episode which was treated with new/increased corticosteroid medication only and resolved, irrespective of any MR4, MMF or azathioprine dose changes; corticosteroid resistant AR was an episode which did not resolve following treatment with corticosteroids, if it was not treated with corticosteroids first but only with antibodies, it was included in this category; corticosteroid resistant AR episodes were further classified into episodes which resolved with further treatment and those which did not respond to further treatment/were ongoing at EOS/withdrawal.
Time to First BCAR Episode Up to 1344 days (3.75 years). The time to first acute rejection episode was defined as the number of days from day 1 (defined as the day of study enrollment) to the first clinical, laboratory or histological signs that were considered to be related to the first acute rejection episode.
Trial Locations
- Locations (101)
Helsinki University Central Hospital
🇫🇮Helsinki, Finland
Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán"
🇲🇽Tlalpan, Mexico
Universitätsspital Zürich
🇨🇭Zurich, Switzerland
ISMETT
🇮🇹Palermo, Italy
AKN Wien
🇦🇹Wien, Austria
University Hospital
🇺🇸Cincinnati, Ohio, United States
Royal Prince Alfred Hospital
🇦🇺Camperdown, New South Wales, Australia
Landeskrankenhaus Innsbruck
🇦🇹Innsbruck, Austria
Princess Alexandra Hospital
🇦🇺Brisbane, Queensland, Australia
Domaine Universitaire du Sart Tillman
🇧🇪Liege, Belgium
Hospital Geral de Bonsucesso
🇧🇷Rio de Janeiro, Brazil
Hospital da Clínicas da UNICAMP
🇧🇷Campinas, Brazil
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Hopital Laennec
🇫🇷Nantes, Cedex 1, France
Charite Campus Virchow Klinikum
🇩🇪Berlin, Germany
Hôpital Edouard Hérriot
🇫🇷Lyon, Cedex 3, France
Medizinische Klink IV
🇩🇪Erlangen, Germany
DISCAT - Centro Trapianti
🇮🇹Genova, Italy
Beaumont Private Clinic
🇮🇪Dublin, Ireland
Ospedali Riuniti di Bergamo
🇮🇹Bergamo, Italy
Herz- und Diabeteszentrum NRW
🇩🇪Bad Oeynhausen, Germany
Universitätsklinik Charité
🇩🇪Berlin, Germany
Universitätklinikum Essen
🇩🇪Essen, Germany
Knappschaftskrankenhaus Bochum-Langendreer
🇩🇪Bochum, Germany
Unita Operativa Trapianto di Fegato e Multiorgano
🇮🇹Bologna, Italy
Azienda Ospedaliera di Padova
🇮🇹Padova, Italy
Jacaranda Hospital
🇿🇦Pretoria, South Africa
Azienda Ospedaliera Policlinico di Modena
🇮🇹Modena, Italy
Klinikum der Universität Regensburg
🇩🇪Regensburg, Germany
Unita Operativa Complessa di Chirurgia dei Trapianti
🇮🇹Siena, Italy
Instituto Mexicano de Transplantes Cuernava
🇲🇽Morelos, Mexico
University of Stellenbosch, Tygerberg Hospital
🇿🇦Tygerberg, South Africa
Hospital Clinic i Provincial
🇪🇸Barcelona, Spain
Hospital Ramon y Cajal
🇪🇸Madrid, Spain
Kings College Hospital
🇬🇧London, United Kingdom
Department of Renal Medicine
🇬🇧Manchester, United Kingdom
Queen Elizabeth Hospital
🇬🇧Edgbaston, United Kingdom
University of Ottawa Heart Institute
🇨🇦Ottawa, Ontario, Canada
Universitäts-Krankenhaus Eppendorf
🇩🇪Hamburg, Germany
Leiter Viszerale Organtransplantation
🇩🇪Heidelberg, Germany
Service de Nephrologie
🇫🇷Nice, Cedex 1, France
Hôpital Rangueil
🇫🇷Toulouse, Cedex 9, France
Hopital Paul Brousse
🇫🇷Villejuif, France
Clinica de Navarra
🇪🇸Pamplona, Spain
DR MED Wolfgang Arns
🇩🇪Koeln, Germany
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
Hospital Erasme
🇧🇪Bruxelles, Belgium
Departement Heelkunde
🇧🇪Gent, Belgium
Cliniques Universitaires St. Luc
🇧🇪Bruxelles, Belgium
Universitair Ziekenhuis Gasthuisberg
🇧🇪Leuven, Belgium
Hospital São Francisco
🇧🇷Porto Alegre, Brazil
Centre Hospitalier de l'Universite de Montreal (CHUM)
🇨🇦Montreal, Quebec, Canada
Vancouver Hospital & Health Sciences Centre
🇨🇦Vancouver, Canada
Institut de Cardiologie de Montréal
🇨🇦Montréal, Quebec, Canada
Royal Victoria Hospital
🇨🇦Montreal, Quebec, Canada
Skejby University Hospital
🇩🇰Århus N, Denmark
IKEM
🇨🇿Praha 4, Czechia
Hôpital Bicêtre
🇫🇷Le Kremlin-Bicêtre, Bicetre Cedex, France
Hotel Dieu
🇫🇷Nantes, Cedex 1, France
Hôpital Calmette
🇫🇷Lille, Cedex, France
Hopital Pontchaillou
🇫🇷Rennes, Cedex, France
Hôpital Beaujon
🇫🇷Clichy, France
Funktionsbereich Nephrologie
🇩🇪Frankfurt/Main, Germany
Klinikum Rechts der Isar
🇩🇪Munchen, Germany
Univ. Klinik und Poliklinik fuer Urologie
🇩🇪Halle, Germany
Semmelweis University of Medicine
🇭🇺Budapest, Hungary
National Liver Transplantation Unit
🇮🇪Dublin, Ireland
Azienda Ospedaliera Ospedale Maggiore di Milano
🇮🇹Milano, Italy
Policlinico Universitario Agostino Gemelli
🇮🇹Roma, Italy
Clinica Chirurgica Universitaria
🇮🇹Udine, Italy
Servicio de Nefrologia
🇪🇸Barcelona, Spain
Christiaan Barnard Memorial Hospital
🇿🇦Cape Town, South Africa
St Augustine's Hospital
🇿🇦Durban, South Africa
Akademisch Ziekenhuis Maastricht
🇳🇱Maastricht, Netherlands
New Zealand Liver Transplant Unit
🇳🇿Auckland, New Zealand
Samodzielny Publiczny Szpital Kliniczny
🇵🇱Szczecin, Poland
Groote Schuur Hospital
🇿🇦Cape Town, South Africa
Hospital General Universitario Gregorio Maranón
🇪🇸Madrid, Spain
Consultas de Trasplante Renal
🇪🇸Madrid, Spain
Hospital Central de Asturias
🇪🇸Oviedo, Spain
SU/Sahlgrenska University Hospital
🇸🇪Gothenburg, Sweden
Hospital Clinico Universitario de Santiago
🇪🇸Santiago de Compostela, Spain
Karolinska University Hospital Huddinge
🇸🇪Stockholm, Sweden
Walsgrove Hospital
🇬🇧Coventry, United Kingdom
Western Infirmary
🇬🇧Glasgow, United Kingdom
Wythenshaw Hospital
🇬🇧Manchester, United Kingdom
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Klinik und Poliklinik fuer Chirurgie
🇩🇪Regensburg, Germany
Irmandade da Santa Casa de Misericordia de Porto Alegre
🇧🇷Porto Alegre, Brazil
Hopital Saint-Eloi
🇫🇷Montpellier, Cedex 05, France
Royal Melbourne Hospital
🇦🇺Melbourne, Victoria, Australia
Hôpital Lapeyronie
🇫🇷Montpellier, Cedex 5, France
University of Alberta
🇨🇦Edmonton, Alberta, Canada
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Hôpital Henri Mondor
🇫🇷Créteil, France
Chu Nord
🇫🇷Grenoble, France
CHU Saint-Etienne
🇫🇷St Etienne, France
Hôpital Hautepierre
🇫🇷Strasbourg, France
Unidad de Trasplante Hepatico
🇪🇸Barcelona, Spain
Hospital de Cruces
🇪🇸Barakaldo, Vizcaya, Spain
The Freeman Hospital
🇬🇧Newcastle upon Tyne, United Kingdom