To Evaluate the Efficacy and Safety of ADVAGRAF® After Treatment With a Tacrolimus in New Liver Transplant Recipients

Study Overview
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Brief Summary
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This study's objective is to evaluate the incidence rate of acute rejection reactions after 24 weeks treatment with ADVAGRAF® following 3 months treatment with tacrolimus in new liver transplant recipients. Treatment conversion will take place from twice daily tacrolimus to once daily tacrolimus (ADVAGRAF) 3 months after transplant in new liver transplant recipients.

Detailed Description
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This is single center,open-label study with ADVAGRAF® Primary endpoint is Incidence rate of biopsy confirmed acute rejection reactions within 24 weeks following conversion+ Incidence rate of acute rejection reactions (%) = number of subjects with at least one acute rejection reaction 1)/total number of subjects in the relevant analysis set * 100 Only those acute rejection reactions confirmed by biopsy will be acceptable as acute rejection reactions. Administration method is following The total daily dose of 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, starting from Day 1 (at least one hour before breakfast or 2 to 3 hours after breakfast). Dose adjustment after conversion On Day 1, the total dose will be converted to 1:1. 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 8ng/ml for 0 to 3 months and then at 5ng/ml or below for 3 to 6 months of study treatment. Duration of treatment The investigational product will be administered for 24 weeks.

Official Title
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A Single Center, Single Arm, Open-label Study to Evaluate the Efficacy and Safety of Tacrolimus Modified Release, ADVAGRAF® After Treatment With a Tacrolimus in New Liver Transplant Recipients

Conditions
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Liver Transplantation

Intervention / Treatment
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* Drug: ADVAGRAF®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: When the Subjects agree informed consent form, Subject should be More than 20 years of age Those who are transplanated liver at a minimum of 10 weeks or Maximum of 14 weeks of baseline Average of tacrorimus trough level is 3-10 ng/mL from transplanted date to before baseline. Female subjects of child bearing potential must have a negative urine or serum pregnancy test prior to enrolment and at the end of study and must agree to practice effective birth control during the study.(The oral contraceptive pill is not allowed to take a female subject) ⑤Subjects are stable clinically in the opinion of the investigator. ⑥Subjects 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: 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. Acute rejection from transplanted date to before baseline Subjects diagnosed new malignant tumor after liver transplantation, with the exception of basalioma or squamous cell carcinoma of the skin that has been treated successfully. Subjects allergic to tacrolimus or investigational product. Subjects are unstable clinically state in the opinion of the investigator. Subjects with any form of substance abuse, psychiatric disorder or condition which, in the opinion of the investigator, may complicate communication with the investigator. ⑦Subjects 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. ⑧Subjects taking forbidden concomitant medications or within 28 days prior to enroll. Subjects who are pregnant or breast-feeding mother. ⑩Subjects known to be HIV positive. ⑪Subjects unlikely to comply with the visits scheduled in the protocol. ⑫Subjects with renal dysfunction on the investigator's point of view or serum creatinine > 1.6mg/dL or GFR(MDRD)<30mL/min in the baseline. ⑬Hepatic dysfunction: rising more than triple the normal range of SGPT/ALT and/or SGOT/AST and/or bilirubin, hepatic cirrhosis

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ADVAGRAF®<br>One arm: Treatment conversion will take place from twice daily tacrolimus to once daily tacrolimus (ADVAGRAF) 3 months after transplant in new liver transplant recipients. | Drug: ADVAGRAF®<br>* Administration method The total daily dose of 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, starting from Day 1 (at least one hour before breakfast or 2 to 3 hours after breakfast). Dose adjustment after conversion On Day 1, the total dose will be converted to 1:1. 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 8ng/ml for 0 to 3 months and then at 5ng/ml or below for 3 to 6 months of study treatment. Duration of treatment The investigational product will be administered for 24 weeks.<br>* Other names: tacrolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of biopsy confirmed acute rejection | Incidence rate of acute rejection reactions (%) = number of subjects with at least one acute rejection reaction 1)/total number of subjects in the relevant analysis set * 100 | 24 weeks within | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of biopsy confirmed acute rejection | Severity of acute rejection reactions is defined as the highest severity in a subject who had at least one acute rejection reaction. | within 24 weeks | 
| Survival rates of subjects and transplanted organs | The survival rate of transplant organs is determined by the loss of transplant organs in the 24th week. Transplant organ loss is defined as re-transplant surgery or death. The date of the transplant's disappearance is the first time one of these events has occurred. | at 24 weeks | 
| compliance | The dosage compliance level is checked by the questionnaire at each visit based on the total amount of the IPs that should have been taken. | at 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADVAGRAF®, liver transplantation, tacrolimus