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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02118896




Registration number
NCT02118896
Ethics application status
Date submitted
17/04/2014
Date registered
21/04/2014
Date last updated
21/02/2019

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2005-005714-20
Secondary ID [2] 0 0
F506-CL-0857
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Transplantation 0 0
Liver Transplantation 0 0
Kidney Transplantation 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - FK506E

Experimental: 1: FK506E (MR4) - 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.


Treatment: Drugs: FK506E
oral

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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participant survival were (Event time: day of death, Censor Time: day of last follow-up (for participants prematurely withdrawn from the study), and day of last visit (for participants completing the study) .
Timepoint [1] 0 0
Up to 5.5 years (66 months (phase II) and 24 months (phase III)).
Primary outcome [2] 0 0
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) .
Timepoint [2] 0 0
Up to 5.5 years ((66 months (phase II) and 30 months (phase III)).
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Up to 6 years.
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Up to 1344 days (3.75 years).
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
From first dose to duration of participation in the study (up to 6 years and 28 days after EOS).

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Pregnant women or nursing mothers.

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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [3] 0 0
Austin Hospital - Heidelberg
Recruitment hospital [4] 0 0
Royal Melbourne Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
4102 - Brisbane
Recruitment postcode(s) [3] 0 0
3084 - Heidelberg
Recruitment postcode(s) [4] 0 0
3050 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Ohio
Country [2] 0 0
Austria
State/province [2] 0 0
Innsbruck
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Austria
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Wien
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Belgium
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Bruxelles
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Belgium
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Gent
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Belgium
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Leuven
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Belgium
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Liege
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Brazil
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Campinas
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Brazil
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Porto Alegre
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Brazil
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Rio de Janeiro
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Canada
State/province [11] 0 0
Alberta
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
Canada
State/province [14] 0 0
Vancouver
Country [15] 0 0
Czechia
State/province [15] 0 0
Praha 4
Country [16] 0 0
Denmark
State/province [16] 0 0
Århus N
Country [17] 0 0
Finland
State/province [17] 0 0
Helsinki
Country [18] 0 0
France
State/province [18] 0 0
Bicetre Cedex
Country [19] 0 0
France
State/province [19] 0 0
Cedex 05
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France
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Cedex 1
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France
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Cedex 3
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France
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Cedex 5
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France
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Cedex 9
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France
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Cedex
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France
State/province [25] 0 0
Clichy
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France
State/province [26] 0 0
Creteil
Country [27] 0 0
France
State/province [27] 0 0
Créteil
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France
State/province [28] 0 0
Grenoble
Country [29] 0 0
France
State/province [29] 0 0
St Etienne
Country [30] 0 0
France
State/province [30] 0 0
Strasbourg
Country [31] 0 0
France
State/province [31] 0 0
Villejuif
Country [32] 0 0
Germany
State/province [32] 0 0
Bad Oeynhausen
Country [33] 0 0
Germany
State/province [33] 0 0
Berlin
Country [34] 0 0
Germany
State/province [34] 0 0
Bochum
Country [35] 0 0
Germany
State/province [35] 0 0
Erlangen
Country [36] 0 0
Germany
State/province [36] 0 0
Essen
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Germany
State/province [37] 0 0
Frankfurt/Main
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Germany
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Halle
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Germany
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Hamburg
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Germany
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Hannover
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Germany
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Heidelberg
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Germany
State/province [42] 0 0
Koeln
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Germany
State/province [43] 0 0
Munchen
Country [44] 0 0
Germany
State/province [44] 0 0
Regensburg
Country [45] 0 0
Hungary
State/province [45] 0 0
Budapest
Country [46] 0 0
Ireland
State/province [46] 0 0
Dublin
Country [47] 0 0
Italy
State/province [47] 0 0
Bergamo
Country [48] 0 0
Italy
State/province [48] 0 0
Bologna
Country [49] 0 0
Italy
State/province [49] 0 0
Genova
Country [50] 0 0
Italy
State/province [50] 0 0
Milano
Country [51] 0 0
Italy
State/province [51] 0 0
Modena
Country [52] 0 0
Italy
State/province [52] 0 0
Padova
Country [53] 0 0
Italy
State/province [53] 0 0
Palermo
Country [54] 0 0
Italy
State/province [54] 0 0
Roma
Country [55] 0 0
Italy
State/province [55] 0 0
Siena
Country [56] 0 0
Italy
State/province [56] 0 0
Udine
Country [57] 0 0
Mexico
State/province [57] 0 0
Morelos
Country [58] 0 0
Mexico
State/province [58] 0 0
Tlalpan
Country [59] 0 0
Netherlands
State/province [59] 0 0
Maastricht
Country [60] 0 0
New Zealand
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Auckland
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Poland
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Bydgoszcz
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Poland
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Szczecin
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South Africa
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Cape Town
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South Africa
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Durban
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South Africa
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Pretoria
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South Africa
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Tygerberg
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Spain
State/province [67] 0 0
Vizcaya
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Oviedo
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Spain
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Pamplona
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Spain
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Santiago de Compostela
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Sweden
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Gothenburg
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Sweden
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Stockholm
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Switzerland
State/province [75] 0 0
Zurich
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United Kingdom
State/province [76] 0 0
Coventry
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United Kingdom
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Edgbaston
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United Kingdom
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Glasgow
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United Kingdom
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London
Country [80] 0 0
United Kingdom
State/province [80] 0 0
Manchester
Country [81] 0 0
United Kingdom
State/province [81] 0 0
Newcastle upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Astellas Pharma Europe Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/show/NCT02118896
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Central Contact
Address 0 0
Astellas Pharma Europe Ltd.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications