Heart TransplantationPhase 3NCT02118896
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 Phase 3 study testing FK506E in people with Heart Transplantation and Liver Transplantation, run by Astellas Pharma Europe Ltd. at 105 sites in 23 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Transplantation, Liver Transplantation, Kidney Transplantation
- What is being tested?
- FK506E
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 850 participants
- Where
- 105 sitesin 23 countries
- Study dates
- 24 Feb 2003to 7 Oct 2009
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Pregnant women or nursing mothers.
- Women unwilling or unable to use adequate contraception during the study.
Trial locations and contacts
105 sites in 23 countries.
105 sites in 23 countries
France17 sites
Hôpital Beaujon
Clichy, 92118
Hôpital Henri Mondor
Créteil, 94000
Hôpital Henri Mondor
Créteil, 94010
Chu Nord
Grenoble, 38043
Hôpital Bicêtre
Le Kremlin-Bicêtre, Bicetre Cedex, 94275
Hôpital Calmette
Lille, Cedex, 59037
Hôpital Edouard Hérriot
Lyon, Cedex 3, 69437
Hopital Saint-Eloi
Montpellier, Cedex 05, 34295
Hôpital Lapeyronie
Montpellier, Cedex 5, 34295
Hopital Laennec
Nantes, Cedex 1, 44093
Hotel Dieu
Nantes, Cedex 1, 44093
Service de Nephrologie
Nice, Cedex 1, 06002
Hopital Pontchaillou
Rennes, Cedex, 35033
CHU Saint-Etienne
Saint-Etienne, 42055
Hôpital Hautepierre
Strasbourg, 67098
Hôpital Rangueil
Toulouse, Cedex 9, 31059
Hopital Paul Brousse
Villejuif, 94804
Germany15 sites
Herz- und Diabeteszentrum NRW
Bad Oeynhausen, 32545
Universitätsklinik Charité
Berlin, 10117
Charite Campus Virchow Klinikum
Berlin, 13353
Knappschaftskrankenhaus Bochum-Langendreer
Bochum, 44892
DR MED Wolfgang Arns
Cologne, 51109
Medizinische Klink IV
Erlangen, 91504
Universitätklinikum Essen
Essen, 45122
Funktionsbereich Nephrologie
Frankfurt am Main, 60590
Univ. Klinik und Poliklinik fuer Urologie
Halle, 06120
Universitäts-Krankenhaus Eppendorf
Hamburg, 20246
Medizinische Hochschule Hannover
Hanover, 30625
Leiter Viszerale Organtransplantation
Heidelberg, 69120
Klinikum Rechts der Isar
München, 81675
Klinik und Poliklinik fuer Chirurgie
Regensburg, 93042
Klinikum der Universität Regensburg
Regensburg, 93053
Spain13 sites
Hospital de Cruces
Barakaldo, Vizcaya, 48903
Servicio de Nefrologia
Barcelona, 08025
Hospital Vall d'Hebron
Barcelona, 08035
Servicio de Nefrologia
Barcelona, 08035
Hospital Clinic i Provincial
Barcelona, 08036
Unidad de Trasplante Hepatico
Barcelona, 08036
Servicio de Nefrologia
Barcelona, 08916
Hospital General Universitario Gregorio Maranón
Madrid, 28007
Hospital Ramon y Cajal
Madrid, 28034
Consultas de Trasplante Renal
Madrid, 28041
Hospital Central de Asturias
Oviedo, 33006
Clinica de Navarra
Pamplona, 31008
Hospital Clinico Universitario de Santiago
Santiago de Compostela, 15706
Italy10 sites
Ospedali Riuniti di Bergamo
Bergamo, 24122
Unita Operativa Trapianto di Fegato e Multiorgano
Bologna, 40138
DISCAT - Centro Trapianti
Genova, 16132
Azienda Ospedaliera Ospedale Maggiore di Milano
Milan, 20122
Azienda Ospedaliera Policlinico di Modena
Modena, 41100
Azienda Ospedaliera di Padova
Padova, 35128
ISMETT
Palermo, 90134
Policlinico Universitario Agostino Gemelli
Roma, 00168
Unita Operativa Complessa di Chirurgia dei Trapianti
Siena, 53100
Clinica Chirurgica Universitaria
Udine, 33100
Canada7 sites
University of Alberta
Edmonton, Alberta, T6G 2B7
London Health Sciences Centre
London, Ontario, N6A 5A5
Institut de Cardiologie de Montréal
Montreal, Quebec, H1T 1C8
Centre Hospitalier de l'Universite de Montreal (CHUM)
Montreal, Quebec, H2X 3J4
Royal Victoria Hospital
Montreal, Quebec, H3A 1A1
University of Ottawa Heart Institute
Ottawa, Ontario, K1Y 4W7
Vancouver Hospital & Health Sciences Centre
Vancouver, V5Z 1L7
United Kingdom7 sites
Walsgrove Hospital
Coventry, CV2 2DX
Queen Elizabeth Hospital
Edgbaston, B15 2TH
Western Infirmary
Glasgow, G11 6NT
Kings College Hospital
London, SE5 9RS
Department of Renal Medicine
Manchester, M13 9WL
Wythenshaw Hospital
Manchester, M23 9LT
The Freeman Hospital
Newcastle upon Tyne, NE7 7DN
Belgium5 sites
Hospital Erasme
Brussels, 1070
Cliniques Universitaires St. Luc
Brussels, 1200
Departement Heelkunde
Ghent, 9000
Universitair Ziekenhuis Gasthuisberg
Leuven, 3000
Domaine Universitaire du Sart Tillman
Liège, 4000
South Africa5 sites
Groote Schuur Hospital
Cape Town, 7925
Christiaan Barnard Memorial Hospital
Cape Town, 8001
St Augustine's Hospital
Durban, 4001
Jacaranda Hospital
Pretoria, 0181
University of Stellenbosch, Tygerberg Hospital
Tygerberg, 7505
Australia4 sites
Princess Alexandra Hospital
Brisbane, Queensland, 4102
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
Austin Hospital
Heidelberg, Victoria, 3084
Royal Melbourne Hospital
Melbourne, Victoria, 3050
Brazil4 sites
Hospital da Clínicas da UNICAMP
Campinas, 13083-888
Hospital São Francisco
Porto Alegre, 90020-090
Irmandade da Santa Casa de Misericordia de Porto Alegre
Porto Alegre, 90020-090
Hospital Geral de Bonsucesso
Rio de Janeiro, 21041-030
Austria2 sites
Landeskrankenhaus Innsbruck
Innsbruck, 6020
AKN Wien
Vienna, 1090
Ireland2 sites
National Liver Transplantation Unit
Dublin, 4
Beaumont Private Clinic
Dublin, 9
Mexico2 sites
Instituto Mexicano de Transplantes Cuernava
Morelos, 62448
Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán"
Tlalpan, 14000
Poland2 sites
Samodzielny Publiczny Szpital Kliniczny
Bydgoszcz, 85-094
Samodzielny Publiczny Szpital Kliniczny
Szczecin, 70-111
Sweden2 sites
SU/Sahlgrenska University Hospital
Gothenburg, 41345
Karolinska University Hospital Huddinge
Stockholm, 14186
About this study
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
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.
Read the 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.
- Being tested
- FK506E
- Keywords
- FK506E, Heart Transplantation, MR4, Tacrolimus, Advagraf, Kidney Transplantation, Renal Transplantation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FK506EDrug
Also called Astagraf XL, Advagraf, Graceptor, MR4
oral
| Study group | Role | What they receive |
|---|---|---|
| 1: FK506E (MR4) | Experimental | 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. Receives: Drug: FK506E |
What is being measured
The primary outcome is the main question the study is designed to answer.
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) .
Measured: 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) .
Measured: Up to 5.5 years ((66 months (phase II) and 30 months (phase III)).
Secondary outcomes (3)
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.
Measured: Up to 6 years.
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.
Measured: Up to 1344 days (3.75 years).
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.
Measured: From first dose to duration of participation in the study (up to 6 years and 28 days after EOS).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2014 (estimated)
- Study start24 Feb 2003
- Primary completion7 Oct 2009
- Study completion7 Oct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Heart TransplantationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 850 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Europe Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Central Contact, Study chair, Astellas Pharma Europe Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02118896
- Sponsor's protocol ID
- F506-CL-0857
- Other IDs
- 2005-005714-20, FG-506-14-02, 2005
- Status last verified
- Oct 2024
- First submitted
- 17 Apr 2014
- Last updated
- 22 Nov 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: 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/.
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02118896
- Acronym / sponsor ID
- F506-CL-0857
- Keywords
- FK506E, Heart Transplantation, MR4, Tacrolimus, Advagraf, Kidney Transplantation, Renal Transplantation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 850 participants (actual)
- Lead sponsor
- Astellas Pharma Europe Ltd.Industry (pharma, biotech, devices)
- Study start
- 24 Feb 2003 (actual)
- Primary completion
- 7 Oct 2009 (actual)
- Study completion
- 7 Oct 2009 (actual)
- First posted
- 21 Apr 2014 (estimated)
- Results
- Posted 15 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1: FK506E (MR4) | Experimental | Drug: FK506ESingle 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (2 listed)
- Pregnant women or nursing mothers.
- Women unwilling or unable to use adequate contraception during the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FK506EAlso: Astagraf XL, Advagraf, Graceptor, MR4oral | Drug | 1: FK506E (MR4) |
Primary outcome
Participant Survival
Time frame: 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
Time frame: 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) .
3 secondary outcomes
Biopsy-confirmed Acute Rejection (BCAR) Episodes
Time frame: Up to 6 years.
Time to First BCAR Episode
Time frame: Up to 1344 days (3.75 years).
Number of Participants With Adverse Events
Time frame: From first dose to duration of participation in the study (up to 6 years and 28 days after EOS).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. 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/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Central Contact study chair
Astellas Pharma Europe Ltd.
105 sites in 23 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing FK506E in people with Heart Transplantation and Liver Transplantation, run by Astellas Pharma Europe Ltd. at 105 sites in 23 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 105 sites in France, Germany, Spain, Italy, Canada and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Mar 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Participant Survival (time frame: Up to 5.5 years (66 months (phase II) and 24 months (phase III)).). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2024.