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

Kidney Transplantation Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02118896
• Other study ID #: F506-CL-0857
• Secondary ID: 2005-005714-20FG
• Status: Completed
• Phase: Phase 3
• Start date: February 24, 2003
• Est. completion date: October 7, 2009

Study information

• Verified date: February 2019
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 850
• Est. completion date: October 7, 2009
• Est. primary completion date: October 7, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Pregnant women or nursing mothers.

• Women unwilling or unable to use adequate contraception during the study.

Related Conditions & MeSH terms

• Heart Transplantation
• Kidney Transplantation
• Liver Transplantation

Intervention

Drug:
• FK506E
oral

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Brisbane	Queensland
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Royal Melbourne Hospital	Melbourne	Victoria
Austria	Landeskrankenhaus Innsbruck	Innsbruck
Austria	AKN Wien	Wien
Belgium	Cliniques Universitaires St. Luc	Bruxelles
Belgium	Hospital Erasme	Bruxelles
Belgium	Departement Heelkunde	Gent
Belgium	Universitair Ziekenhuis Gasthuisberg	Leuven
Belgium	Domaine Universitaire du Sart Tillman	Liege
Brazil	Hospital da Clínicas da UNICAMP	Campinas
Brazil	Hospital São Francisco	Porto Alegre
Brazil	Irmandade da Santa Casa de Misericordia de Porto Alegre	Porto Alegre
Brazil	Hospital Geral de Bonsucesso	Rio de Janeiro
Canada	University of Alberta	Edmonton	Alberta
Canada	London Health Sciences Centre	London	Ontario
Canada	Centre Hospitalier de l'Universite de Montreal (CHUM)	Montreal	Quebec
Canada	Royal Victoria Hospital	Montreal	Quebec
Canada	Institut de Cardiologie de Montréal	Montréal	Quebec
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
Canada	Vancouver Hospital & Health Sciences Centre	Vancouver
Czechia	IKEM	Praha 4
Denmark	Skejby University Hospital	Århus N
Finland	Helsinki University Central Hospital	Helsinki
France	Hôpital Beaujon	Clichy
France	Hôpital Henri Mondor	Creteil
France	Hôpital Henri Mondor	Créteil
France	Chu Nord	Grenoble
France	Hôpital Bicêtre	Le Kremlin-Bicêtre	Bicetre Cedex
France	Hôpital Calmette	Lille	Cedex
France	Hôpital Edouard Hérriot	Lyon	Cedex 3
France	Hôpital Lapeyronie	Montpellier	Cedex 5
France	Hopital Saint-Eloi	Montpellier	Cedex 05
France	Hopital Laennec	Nantes	Cedex 1
France	Hotel Dieu	Nantes	Cedex 1
France	Service de Nephrologie	Nice	Cedex 1
France	Hopital Pontchaillou	Rennes	Cedex
France	CHU Saint-Etienne	St Etienne
France	Hôpital Hautepierre	Strasbourg
France	Hôpital Rangueil	Toulouse	Cedex 9
France	Hopital Paul Brousse	Villejuif
Germany	Herz- und Diabeteszentrum NRW	Bad Oeynhausen
Germany	Charite Campus Virchow Klinikum	Berlin
Germany	Universitätsklinik Charité	Berlin
Germany	Knappschaftskrankenhaus Bochum-Langendreer	Bochum
Germany	Medizinische Klink IV	Erlangen
Germany	Universitätklinikum Essen	Essen
Germany	Funktionsbereich Nephrologie	Frankfurt/Main
Germany	Univ. Klinik und Poliklinik fuer Urologie	Halle
Germany	Universitäts-Krankenhaus Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Leiter Viszerale Organtransplantation	Heidelberg
Germany	DR MED Wolfgang Arns	Koeln
Germany	Klinikum Rechts der Isar	Munchen
Germany	Klinik und Poliklinik fuer Chirurgie	Regensburg
Germany	Klinikum der Universität Regensburg	Regensburg
Hungary	Semmelweis University of Medicine	Budapest
Ireland	Beaumont Private Clinic	Dublin
Ireland	National Liver Transplantation Unit	Dublin
Italy	Ospedali Riuniti di Bergamo	Bergamo
Italy	Unita Operativa Trapianto di Fegato e Multiorgano	Bologna
Italy	DISCAT - Centro Trapianti	Genova
Italy	Azienda Ospedaliera Ospedale Maggiore di Milano	Milano
Italy	Azienda Ospedaliera Policlinico di Modena	Modena
Italy	Azienda Ospedaliera di Padova	Padova
Italy	ISMETT	Palermo
Italy	Policlinico Universitario Agostino Gemelli	Roma
Italy	Unita Operativa Complessa di Chirurgia dei Trapianti	Siena
Italy	Clinica Chirurgica Universitaria	Udine
Mexico	Instituto Mexicano de Transplantes Cuernava	Morelos
Mexico	Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán"	Tlalpan
Netherlands	Akademisch Ziekenhuis Maastricht	Maastricht
New Zealand	New Zealand Liver Transplant Unit	Auckland
Poland	Samodzielny Publiczny Szpital Kliniczny	Bydgoszcz
Poland	Samodzielny Publiczny Szpital Kliniczny	Szczecin
South Africa	Christiaan Barnard Memorial Hospital	Cape Town
South Africa	Groote Schuur Hospital	Cape Town
South Africa	St Augustine's Hospital	Durban
South Africa	Jacaranda Hospital	Pretoria
South Africa	University of Stellenbosch, Tygerberg Hospital	Tygerberg
Spain	Hospital de Cruces	Barakaldo	Vizcaya
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Servicio de Nefrologia	Barcelona
Spain	Servicio de Nefrologia	Barcelona
Spain	Servicio de Nefrologia	Barcelona
Spain	Unidad de Trasplante Hepatico	Barcelona
Spain	Consultas de Trasplante Renal	Madrid
Spain	Hospital General Universitario Gregorio Maranón	Madrid
Spain	Hospital Ramon y Cajal	Madrid
Spain	Hospital Central de Asturias	Oviedo
Spain	Clinica de Navarra	Pamplona
Spain	Hospital Clinico Universitario de Santiago	Santiago de Compostela
Sweden	SU/Sahlgrenska University Hospital	Gothenburg
Sweden	Karolinska University Hospital Huddinge	Stockholm
Switzerland	Universitätsspital Zürich	Zurich
United Kingdom	Walsgrove Hospital	Coventry
United Kingdom	Queen Elizabeth Hospital	Edgbaston
United Kingdom	Western Infirmary	Glasgow
United Kingdom	Kings College Hospital	London
United Kingdom	Department of Renal Medicine	Manchester
United Kingdom	Wythenshaw Hospital	Manchester
United Kingdom	The Freeman Hospital	Newcastle upon Tyne
United States	University Hospital	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Europe Ltd.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Czechia,  Denmark,  Finland,  France,  Germany,  Hungary,  Ireland,  Italy,  Mexico,  Netherlands,  New Zealand,  Poland,  South Africa,  Spain,  Sweden,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)).
Primary	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	Biopsy-confirmed Acute Rejection (BCAR) Episodes	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.	Up to 6 years.
Secondary	Time to First BCAR Episode	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.	Up to 1344 days (3.75 years).
Secondary	Number of Participants With Adverse Events	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.	From first dose to duration of participation in the study (up to 6 years and 28 days after EOS).

External Links

•   Link to Results on the Astellas Clinical Study Results website