Evaluate the Efficacy and Safety of the ADVAGRAF®

NCT ID: NCT04763096

Last Updated: 2021-02-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

101 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-11-30

Study Completion Date

2020-04-30

Brief Summary

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The primary objective of this study is to evaluate the efficacy of 6-month treatment with Advagraf® converted from 12-month treatment with tacrolimus in stable liver transplant recipients.

The secondary objective of this study is to evaluate severity of acute rejection confirmed by biopsy in 24 weeks, incidence of chronic rejection, patient and graft survival rates in 24 weeks, incidence of adverse events, blood pressure, tacrolimus trough level, drug compliance, and adherence.

Detailed Description

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This is single-center, single-group, open-label study, phase 4 IIT. The Subject is transplantated liver at a minimum of 12 month of screening and at least 12 month Treatment with a Tacrolimus stably And start screening after obtain consent to participate in clinical trials, if appropriate in the selection criteria do not apply to the exclusion criteria are enrolled in clinical trials.

Administration method is following : The total daily dose of -1 tacrolimus will be converted to 1:1 (mg:mg) and the total daily dose of ADVAGRAF® will be administered only once daily in the morning for 24 weeks, starting from Day 0.

Researchers must check the blood concentration of tacrolimus at each visit and adjust the dose to achieve the blood concentration maintaining at 5\~10ng/ml of study treatment.

Duration of treatment : The investigational product will be administered for 24 weeks.

Tacrorimus blood level is 3-10 ng/ml for 6 months prior to screening and during the maintenance therapy. It is recommended to check the blood concentration of tacrolimus at each visit and adjust the dose to achieve the blood concentration maintaining at 5\~10ng/ml of study treatment. (The lowest blood levels shall be adjusted at the discretion of the researchers, taking a blood sample is carried out in the morning before have of Investigational Product)

Subjects, who participated in this clinical trial, are scheduled up to 5 times, and it will be proceed for 24 weeks. (screening and baseline, 3 weeks, 12 weeks, 24 weeks) admitted for 24 weeks including a screening visit.

Conditions

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Evidence of Liver Transplantation

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

HEALTH_SERVICES_RESEARCH

Blinding Strategy

NONE

Study Groups

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tacrolimus

conversion to Advagraf

Group Type EXPERIMENTAL

Advagraf

Intervention Type DRUG

Researchers must check the blood concentration of tacrolimus at each visit and adjust the dose to achieve the blood concentration maintaining at 5\~10ng/ml of study treatment. Duration of treatment The investigational product will be administered for 24 weeks. (The lowest blood levels shall be adjusted at the discretion of the researchers, taking a blood sample is carried out in the morning before administrated of Investigational Product)

Tacrolimus blood level is 3-10 ng/ml for 6 months prior to screening and during the maintenance therapy.

( ① -1day to enrollment : swich to the day before ADVAGRAF®, ② 0day to enrollment : the day swich to ADVAGRAF® )

Duration of treatment the investigational product will be administered for 24 weeks.

Interventions

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Advagraf

Researchers must check the blood concentration of tacrolimus at each visit and adjust the dose to achieve the blood concentration maintaining at 5\~10ng/ml of study treatment. Duration of treatment The investigational product will be administered for 24 weeks. (The lowest blood levels shall be adjusted at the discretion of the researchers, taking a blood sample is carried out in the morning before administrated of Investigational Product)

Tacrolimus blood level is 3-10 ng/ml for 6 months prior to screening and during the maintenance therapy.

( ① -1day to enrollment : swich to the day before ADVAGRAF®, ② 0day to enrollment : the day swich to ADVAGRAF® )

Duration of treatment the investigational product will be administered for 24 weeks.

Intervention Type DRUG

Other Intervention Names

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tacrolimus

Eligibility Criteria

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Inclusion Criteria

1. Aged between 19 and 80 years old
2. Those who were transplantated liver at a minimum of 12 month of screening and after 12 month Treatment with a Tacrolimus stably.(Brain dead transplantation or biological transplant no values)
3. tacrolimus blood everage level is 3-10 ng/ml for at least 6 months prior to screening.
4. Female subjects of child bearing potential must have a negative urine or serum pregnancy test prior to enrollment and at the end of study and must agree to practice effective birth control during the study.
5. Subjects are stable clinically in the opinion of the investigator.
6. Subjects capable of understanding the purpose and risks of the study, having been fully informed and has given written informed consent to participate in the study

Exclusion Criteria

1. Subjects having previously received an organ transplant excluding liver transplant. Or Subjects receiving an auxiliary graft or in whom a bio-artificial liver(cell system) has been used.
2. Acute rejection confirmed by histologic response or the patient had chronic rejection
3. Subjects diagnosed new malignant tumor before the pre-screening within five years , with the exception of basalioma or squamous cell carcinoma or carcinoma in situ of the skin that has been treated successfully.
4. Subjects allergic to tacrolimus or investigational product.
5. Subjects are unstable clinically state in the opinion of the investigator.
6. Subjects with any form of substance abuse, psychiatric disorder or condition which, in the opinion of the investigator, may complicate communication with the investigator.
7. Subjects participating or having participated in another clinical trial and/or those taking or having taken an investigational / non-registered drug in the past 28 days.
8. Subjects taking forbidden concomitant medications or within 28 days prior to enroll.
9. Subjects who are pregnant or breast-feeding mother.
10. Subjects unlikely to comply with the visits scheduled in the protocol.
11. Subjects with renal dysfunction on the investigator's point of view or serum creatinine \> 1.6mg/dL or GFR(MDRD)\<30mL/min in the baseline.
12. Hepatic dysfunction: rising more than double the normal range of SGPT/ALT and/or SGOT/AST and/or bilirubin, hepatic cirrhosis
Minimum Eligible Age

19 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Asan Medical Center

OTHER

Sponsor Role collaborator

Linical Korea

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ki Won Song, doctral

Role: PRINCIPAL_INVESTIGATOR

Asan Medical Center, Hepatobiliary, Liver Transplantion Surgery center

Locations

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Seoul Asan Medical Center

Seoul, , South Korea

Site Status

Countries

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South Korea

References

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Bunzel B, Laederach-Hofmann K. Solid organ transplantation: are there predictors for posttransplant noncompliance? A literature overview. Transplantation. 2000 Sep 15;70(5):711-6. doi: 10.1097/00007890-200009150-00001.

Reference Type RESULT
PMID: 11003346 (View on PubMed)

Laederach-Hofmann K, Bunzel B. Noncompliance in organ transplant recipients: a literature review. Gen Hosp Psychiatry. 2000 Nov-Dec;22(6):412-24. doi: 10.1016/s0163-8343(00)00098-0.

Reference Type RESULT
PMID: 11072057 (View on PubMed)

Schweizer RT, Rovelli M, Palmeri D, Vossler E, Hull D, Bartus S. Noncompliance in organ transplant recipients. Transplantation. 1990 Feb;49(2):374-7. doi: 10.1097/00007890-199002000-00029.

Reference Type RESULT
PMID: 2305467 (View on PubMed)

Jain AB, Kashyap R, Rakela J, Starzl TE, Fung JJ. Primary adult liver transplantation under tacrolimus: more than 90 months actual follow-up survival and adverse events. Liver Transpl Surg. 1999 Mar;5(2):144-50. doi: 10.1002/lt.500050209.

Reference Type RESULT
PMID: 10071354 (View on PubMed)

Dopazo C, Rodriguez R, Llado L, Calatayud D, Castells L, Ramos E, Molina V, Garcia R, Fabregat J, Charco R. Successful conversion from twice-daily to once-daily tacrolimus in liver transplantation: observational multicenter study. Clin Transplant. 2012 Jan-Feb;26(1):E32-7. doi: 10.1111/j.1399-0012.2011.01521.x. Epub 2011 Sep 30.

Reference Type RESULT
PMID: 21958123 (View on PubMed)

Trunecka P, Boillot O, Seehofer D, Pinna AD, Fischer L, Ericzon BG, Troisi RI, Baccarani U, Ortiz de Urbina J, Wall W; Tacrolimus Prolonged Release Liver Study Group. Once-daily prolonged-release tacrolimus (ADVAGRAF) versus twice-daily tacrolimus (PROGRAF) in liver transplantation. Am J Transplant. 2010 Oct;10(10):2313-23. doi: 10.1111/j.1600-6143.2010.03255.x. Epub 2010 Sep 14.

Reference Type RESULT
PMID: 20840481 (View on PubMed)

Comuzzi C, Lorenzin D, Rossetto A, Faraci MG, Nicolini D, Garelli P, Bresadola V, Toniutto P, Soardo G, Baroni GS, Adani GL, Risaliti A, Baccarani U. Safety of conversion from twice-daily tacrolimus (Prograf) to once-daily prolonged-release tacrolimus (Advagraf) in stable liver transplant recipients. Transplant Proc. 2010 May;42(4):1320-1. doi: 10.1016/j.transproceed.2010.03.106.

Reference Type RESULT
PMID: 20534291 (View on PubMed)

Merli M, Di Menna S, Giusto M, Giannelli V, Lucidi C, Loria I, Ginanni Corradini S, Mennini G, Rossi M. Conversion from twice-daily to once-daily tacrolimus administration in liver transplant patient. Transplant Proc. 2010 May;42(4):1322-4. doi: 10.1016/j.transproceed.2010.04.012.

Reference Type RESULT
PMID: 20534292 (View on PubMed)

Marin-Gomez LM, Gomez-Bravo MA, Alamo-Martinez JA, Barrera-Pulido L, Bernal Bellido C, Suarez Artacho G, Pascasio JM. Evaluation of clinical safety of conversion to Advagraf therapy in liver transplant recipients: observational study. Transplant Proc. 2009 Jul-Aug;41(6):2184-6. doi: 10.1016/j.transproceed.2009.06.085.

Reference Type RESULT
PMID: 19715867 (View on PubMed)

Kim SH, Lee SD, Kim YK, Park SJ. Conversion of twice-daily to once-daily tacrolimus is safe in stable adult living donor liver transplant recipients. Hepatobiliary Pancreat Dis Int. 2015 Aug;14(4):374-9. doi: 10.1016/s1499-3872(15)60378-2.

Reference Type RESULT
PMID: 26256081 (View on PubMed)

Related Links

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https://www.ncbi.nlm.nih.gov/pubmed/11003346

test link(2000 Sep 15;70(5):711-6.)

https://www.ncbi.nlm.nih.gov/pubmed/11072057

test link(2000 Nov-Dec;22(6):412-24.)

https://www.ncbi.nlm.nih.gov/pubmed/2305467

test link(1990 Feb;49(2):374-7.)

https://www.ncbi.nlm.nih.gov/pubmed/10071354

test link(1999 Mar;5(2):144-50.)

https://www.ncbi.nlm.nih.gov/pubmed/21958123

test link(2012 Jan-Feb;26(1):E32-7. doi: 10.1111/j.1399-0012.2011.01521.x. Epub 2011 Sep 30.)

https://www.ncbi.nlm.nih.gov/pubmed/20840481

test link(2010 Oct;10(10):2313-23. doi: 10.1111/j.1600-6143.2010.03255.x. Epub 2010 Sep 14.)

https://www.ncbi.nlm.nih.gov/pubmed/20534291

test link( 2010 May;42(4):1320-1. doi: 10.1016/j.transproceed.2010.03.106.)

https://www.ncbi.nlm.nih.gov/pubmed/20534292

test link(2010 May;42(4):1322-4. doi: 10.1016/j.transproceed.2010.04.012.)

https://www.ncbi.nlm.nih.gov/pubmed/19715867

test link(2009 Jul-Aug;41(6):2184-6. doi: 10.1016/j.transproceed.2009.06.085.)

https://www.ncbi.nlm.nih.gov/pubmed/26256081

test link(2015 Aug;14(4):374-9.)

Other Identifiers

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STABLE

Identifier Type: -

Identifier Source: org_study_id

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