A Study to Assess the Pharmacokinetics, Safety and Efficacy of Advagraf and Prograf in de Novo Liver Transplantation

Study Overview
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Brief Summary
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The purpose of this study is to investigate and compare the pharmacokinetic parameters of tacrolimus from Advagraf and Prograf in de nove living donor liver transplant recipients.

Official Title
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A Phase IV, Randomized, Open-label, Comparative, Single-center Study to Assess the Pharmacokinetics, Safety and Efficacy of Advagraf® (Modified Release Tacrolimus) and Prograf® (Tacrolimus) in de Novo Living Donor Liver Transplant Recipients

Conditions
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Liver Transplantation

Intervention / Treatment
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* Drug: Advagraf
* Drug: Prograf
* Drug: Prograf


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: subject receiving a primary, partial liver graft from a living donor subject must receive the first dose of tacrolimus and corticosteroids after operation and are expected to be maintained on tacrolimus throughout the study. MMF could be combined Exclusion Criteria: subjects receiving a multi-organ transplant or having previously received an organ transplant (including liver re-transplantation) subjects receiving an auxiliary graft or in whom a bio-artificial liver (cell system) has been used subjects allergic or intolerant to macrolide antibiotics or tacrolimus subjects requiring immunosuppressive treatment and / or systemic chemotherapy prior to transplantation subjects with malignancies or a history of malignancy within the last 5 years, with the exception of those with basalioma or squamous cell carcinoma of the skin subjects with systemic infection requiring treatment, except viral hepatitis subjects with severe diarrhoea, vomiting, active peptic ulcer or gastrointestinal disorder that may affect the absorption of tacrolimus subjects with serum creatinine > 1.5mg/dl subjects taking or having taken potassium preserved diuretics subjects with any form of substance abuse, psychiatric disorder or condition which, in the opinion of the investigator, may complicate communication with the investigator 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 subjects or donors known to be HIV positive donors known to be HBV, HCV positive and/or IgM positive of CMV, EBV

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Intravenous Prograf therapy followed by oral Advagraf therapy | Drug: Advagraf<br>* oral<br>* Other names: modified release tacrolimus;Drug: Prograf<br>* intravenous<br>* Other names: FK506;|
| Active Comparator: Arm 2<br>Intravenous Prograf therapy followed by oral Prograf therapy | Drug: Prograf<br>* oral<br>* Other names: tacrolimus;Drug: Prograf<br>* intravenous<br>* Other names: FK506;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-24 (Area under the curve for 24 hours) of tacrolimus plasma concentration |  | Day 6 and day 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (maximum concentration) of tacrolimus plasma concentration |  | Day 6 and day 21 | 
| Incidence of the composite event: graft loss (defined as re-transplantation or death) or biopsy confirmed acute rejection (BCAR) |  | up to 24 weeks | 
| Time to first incidence of the composite event: graft loss (defined as re-transplantation or death) or biopsy confirmed acute rejection (BCAR) |  | up to 24 weeks | 
| Safety assessed by the incidence of adverse events and lab-tests |  | up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advagraf, prograf, living donor liver transplantation, FK506, Immunosuppressant