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 was transplanated liver at a minimum of 10 weeks or Maximum of 14 weeks before the baseline Average of tacrorimus minimum blood concenration level is 3-10 ng/mL from transplanted date to baseline. Female subjects who have child bearing potential must have a negative at urine or serum pregnancy test prior to enrollment and must agree to practice effective contraceptive measures during the study.(The oral contraceptive pill is not allowed to take a female subject) Subjects who are clinically stable judged by investigator. 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: Subjects previously received an organ transplantation excluding liver transplantation. Or Subjects received an auxiliary graft or bioartificial liver(cell system). Recently there was acute rejection from the day of liver transplantation to baseline If the onset of a new malignant cancer after liver transplantation is diagnosed, well treated basal cell carcinoma or squamous cell carcinoma is classified as an exception When it is known that there is a hypersensitivity reaction to the ingredients of tacrolimus or the test drug In the opinion of the investigator, there is an unstable medical condition that can affect the purpose of the clinical trial In the event of material abuse, mental disorder or anything that can not smoothly communicate with the inverstigator in the opinion of the investigator Currently, if subjects are participating in other clinical trials or if subjects receive another drug for clinical trials within 28 days before baseline If subjects have received a prohibited combination therapy currently or within 28 days before the baseline Pregnant or lactating women If known for HIV-positive When there is a high possibility that subject will not be able to obey the visit schedule planned in protocol Those who have clinically significant renal dysfunction judged by the investigator or at baseline serum creatinine level exceeds 1.6 mg / dL or GFR (MDRD) is less than 30 mL / min Those who have clinically significant liver function disorder judged by the investigator or at the baseline, the values of SGPT / ALT and / or SGOT / AST and / or bilirubin are more than three times the upper limit of the laboratory normal range When raised

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 placefrom 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 acute rejection reaction confirmed by biopsy within 24 weeks after conversion | Incidence rate of acute rejection reaction (%) = The number of subjects with at least one acute rejection reaction / Total number of subjects included in the analysis group * 100 number of subjects in the relevant analysis set * 100 | within 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of acute rejection reaction confirmed by biopsy within 24 weeks after conversion | 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 after conversion |  | at week 24 | 
| Survival rate of transplanted organs after conversion |  | at week 24 | 
| Blood concentration of tacrolimus |  | at week -4, week 0, week 2, week 4, week 8, week 16 and week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADVAGRAF®, Liver Transplantation, tacrolimus