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
A Long-term Follow up Study to Evaluate the Safety and Efficacy in Transplant Recipients Treated With Modified Release Tacrolimus, FK506E (MR4), Based Immunosuppression Regimen
3 other identifiers
interventional
850
22 countries
101
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Feb 2003
Longer than P75 for phase_3
101 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 24, 2003
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 7, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
October 7, 2009
CompletedFirst Submitted
Initial submission to the registry
April 17, 2014
CompletedFirst Posted
Study publicly available on registry
April 21, 2014
CompletedResults Posted
Study results publicly available
March 15, 2016
CompletedNovember 22, 2024
October 1, 2024
6.6 years
April 17, 2014
January 7, 2016
October 30, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Participant Survival
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participant survival were (Event time: day of death, Censor Time: day of last follow-up (for participants prematurely withdrawn from the study), and day of last visit (for participants completing the study) .
Up to 5.5 years (66 months (phase II) and 24 months (phase III)).
Graft Survival
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) .
Up to 5.5 years ((66 months (phase II) and 30 months (phase III)).
Secondary Outcomes (3)
Biopsy-confirmed Acute Rejection (BCAR) Episodes
Up to 6 years.
Time to First BCAR Episode
Up to 1344 days (3.75 years).
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).
Study Arms (1)
1: FK506E (MR4)
EXPERIMENTALSingle 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.
Interventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- Pregnant women or nursing mothers.
- Women unwilling or unable to use adequate contraception during the study.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (105)
University Hospital
Cincinnati, Ohio, 45267-0542, United States
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050, Australia
Princess Alexandra Hospital
Brisbane, Queensland, 4102, Australia
Austin Hospital
Heidelberg, Victoria, 3084, Australia
Royal Melbourne Hospital
Melbourne, Victoria, 3050, Australia
Landeskrankenhaus Innsbruck
Innsbruck, 6020, Austria
AKN Wien
Vienna, 1090, Austria
Hospital Erasme
Brussels, 1070, Belgium
Cliniques Universitaires St. Luc
Brussels, 1200, Belgium
Departement Heelkunde
Ghent, 9000, Belgium
Universitair Ziekenhuis Gasthuisberg
Leuven, 3000, Belgium
Domaine Universitaire du Sart Tillman
Liège, 4000, Belgium
Hospital da Clínicas da UNICAMP
Campinas, 13083-888, Brazil
Hospital São Francisco
Porto Alegre, 90020-090, Brazil
Irmandade da Santa Casa de Misericordia de Porto Alegre
Porto Alegre, 90020-090, Brazil
Hospital Geral de Bonsucesso
Rio de Janeiro, 21041-030, Brazil
University of Alberta
Edmonton, Alberta, T6G 2B7, Canada
London Health Sciences Centre
London, Ontario, N6A 5A5, Canada
University of Ottawa Heart Institute
Ottawa, Ontario, K1Y 4W7, Canada
Institut de Cardiologie de Montréal
Montreal, Quebec, H1T 1C8, Canada
Centre Hospitalier de l'Universite de Montreal (CHUM)
Montreal, Quebec, H2X 3J4, Canada
Royal Victoria Hospital
Montreal, Quebec, H3A 1A1, Canada
Vancouver Hospital & Health Sciences Centre
Vancouver, V5Z 1L7, Canada
IKEM
Prague, 14021, Czechia
Skejby University Hospital
Århus N, 8200, Denmark
Helsinki University Central Hospital
Helsinki, 00130, Finland
Hôpital Bicêtre
Le Kremlin-Bicêtre, Bicetre Cedex, 94275, France
Hopital Saint-Eloi
Montpellier, Cedex 05, 34295, France
Hopital Laennec
Nantes, Cedex 1, 44093, France
Hotel Dieu
Nantes, Cedex 1, 44093, France
Service de Nephrologie
Nice, Cedex 1, 06002, France
Hôpital Edouard Hérriot
Lyon, Cedex 3, 69437, France
Hôpital Lapeyronie
Montpellier, Cedex 5, 34295, France
Hôpital Rangueil
Toulouse, Cedex 9, 31059, France
Hôpital Calmette
Lille, Cedex, 59037, France
Hopital Pontchaillou
Rennes, Cedex, 35033, France
Hôpital Beaujon
Clichy, 92118, France
Hôpital Henri Mondor
Créteil, 94000, France
Hôpital Henri Mondor
Créteil, 94010, France
Chu Nord
Grenoble, 38043, France
CHU Saint-Etienne
Saint-Etienne, 42055, France
Hôpital Hautepierre
Strasbourg, 67098, France
Hopital Paul Brousse
Villejuif, 94804, France
Herz- und Diabeteszentrum NRW
Bad Oeynhausen, 32545, Germany
Universitätsklinik Charité
Berlin, 10117, Germany
Charite Campus Virchow Klinikum
Berlin, 13353, Germany
Knappschaftskrankenhaus Bochum-Langendreer
Bochum, 44892, Germany
DR MED Wolfgang Arns
Cologne, 51109, Germany
Medizinische Klink IV
Erlangen, 91504, Germany
Universitätklinikum Essen
Essen, 45122, Germany
Funktionsbereich Nephrologie
Frankfurt am Main, 60590, Germany
Univ. Klinik und Poliklinik fuer Urologie
Halle, 06120, Germany
Universitäts-Krankenhaus Eppendorf
Hamburg, 20246, Germany
Medizinische Hochschule Hannover
Hanover, 30625, Germany
Leiter Viszerale Organtransplantation
Heidelberg, 69120, Germany
Klinikum Rechts der Isar
München, 81675, Germany
Klinik und Poliklinik fuer Chirurgie
Regensburg, 93042, Germany
Klinikum der Universität Regensburg
Regensburg, 93053, Germany
Semmelweis University of Medicine
Budapest, 1082, Hungary
National Liver Transplantation Unit
Dublin, 4, Ireland
Beaumont Private Clinic
Dublin, 9, Ireland
Ospedali Riuniti di Bergamo
Bergamo, 24122, Italy
Unita Operativa Trapianto di Fegato e Multiorgano
Bologna, 40138, Italy
DISCAT - Centro Trapianti
Genova, 16132, Italy
Azienda Ospedaliera Ospedale Maggiore di Milano
Milan, 20122, Italy
Azienda Ospedaliera Policlinico di Modena
Modena, 41100, Italy
Azienda Ospedaliera di Padova
Padua, 35128, Italy
ISMETT
Palermo, 90134, Italy
Policlinico Universitario Agostino Gemelli
Roma, 00168, Italy
Unita Operativa Complessa di Chirurgia dei Trapianti
Siena, 53100, Italy
Clinica Chirurgica Universitaria
Udine, 33100, Italy
Instituto Mexicano de Transplantes Cuernava
Morelos, 62448, Mexico
Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán"
Tlalpan, 14000, Mexico
Akademisch Ziekenhuis Maastricht
Maastricht, 6229, Netherlands
New Zealand Liver Transplant Unit
Auckland, New Zealand
Samodzielny Publiczny Szpital Kliniczny
Bydgoszcz, 85-094, Poland
Samodzielny Publiczny Szpital Kliniczny
Szczecin, 70-111, Poland
Groote Schuur Hospital
Cape Town, 7925, South Africa
Christiaan Barnard Memorial Hospital
Cape Town, 8001, South Africa
St Augustine's Hospital
Durban, 4001, South Africa
Jacaranda Hospital
Pretoria, 0181, South Africa
University of Stellenbosch, Tygerberg Hospital
Tygerberg, 7505, South Africa
Hospital de Cruces
Barakaldo, Vizcaya, 48903, Spain
Servicio de Nefrologia
Barcelona, 08025, Spain
Hospital Vall d'Hebron
Barcelona, 08035, Spain
Servicio de Nefrologia
Barcelona, 08035, Spain
Hospital Clinic i Provincial
Barcelona, 08036, Spain
Unidad de Trasplante Hepatico
Barcelona, 08036, Spain
Servicio de Nefrologia
Barcelona, 08916, Spain
Hospital General Universitario Gregorio Maranón
Madrid, 28007, Spain
Hospital Ramon y Cajal
Madrid, 28034, Spain
Consultas de Trasplante Renal
Madrid, 28041, Spain
Hospital Central de Asturias
Oviedo, 33006, Spain
Clinica de Navarra
Pamplona, 31008, Spain
Hospital Clinico Universitario de Santiago
Santiago de Compostela, 15706, Spain
SU/Sahlgrenska University Hospital
Gothenburg, 41345, Sweden
Karolinska University Hospital Huddinge
Stockholm, 14186, Sweden
Universitätsspital Zürich
Zurich, 8091, Switzerland
Walsgrove Hospital
Coventry, CV2 2DX, United Kingdom
Queen Elizabeth Hospital
Edgbaston, B15 2TH, United Kingdom
Western Infirmary
Glasgow, G11 6NT, United Kingdom
Kings College Hospital
London, SE5 9RS, United Kingdom
Department of Renal Medicine
Manchester, M13 9WL, United Kingdom
Wythenshaw Hospital
Manchester, M23 9LT, United Kingdom
The Freeman Hospital
Newcastle upon Tyne, NE7 7DN, United Kingdom
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Limitations and Caveats
No Kaplan-Meier estimates for PMR-EC-1210 due to the short subject participation period and the low number of subjects.
Results Point of Contact
- Title
- Clinical Trial Disclosure
- Organization
- Astellas Pharma Europe Limited
Study Officials
- STUDY CHAIR
Central Contact
Astellas Pharma Europe Ltd.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 17, 2014
First Posted
April 21, 2014
Study Start
February 24, 2003
Primary Completion
October 7, 2009
Study Completion
October 7, 2009
Last Updated
November 22, 2024
Results First Posted
March 15, 2016
Record last verified: 2024-10
Data Sharing
- IPD Sharing
- Will not share
Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.