A Study of CellCept (Mycophenolate Mofetil) Combined With Calcineurin Inhibitors in Liver Transplant Patients.

Study Overview
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Brief Summary
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This 2 arm study will compare the efficacy and safety of switching to CellCept combined with different regimens of reduced calcineurin inhibitors (CNI) in patients with liver transplants. Patients currently receiving CNI treatment will be randomized into one of 2 groups to receive either 1) CellCept 2.0g/day po bid + 50% reduction of CNI from baseline or 2) CellCept 2.0g/day po bid + >=75% reduction of CNI from baseline. The anticipated time on study treatment is 1 year, and the target sample size is <100 individuals.

Official Title
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A Randomized, Open Label Study Comparing the Effect of CellCept Combined With 2 Regimens of Reduced Calcineurin Inhibitors on Kidney Function in Liver Transplant Patients

Conditions
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Liver Transplantation

Intervention / Treatment
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* Drug: Mycophenolate mofetil
* Drug: CNI (50%)
* Drug: CNI (≥75%)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >=18 years of age; single organ recipients of liver allograft; CNI-based immunosuppressive regimen prior to study entry and regimen adjustment; >=6 months post-transplant, with renal dysfunction (serum creatinine 140-300micromol/L at entry); negative pregnancy test for women of childbearing potential; contraception must be taken before beginning study drug therapy and until 6 weeks after last dose of study medication. Exclusion Criteria: treatment with CellCept or any other product which delivers mycophenolic acid within the 3 months prior to the recent switch to CellCept relevant for enrollment; known contraindications to CNI, corticosteroids or CellCept.

Ages Eligible for Study
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Minimum Age: 18 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: MMF, 50% CNI Reduction<br>Participants received mycophenolate mofetil (MMF), 1.5 to 2.0 grams (g) daily, orally (PO), twice per day (BID) from baseline (BL) to Week 52. Participants also received a 50 percent (%) reduced dose of calcineurin inhibitor (CNI) from BL to Week 52. | Drug: Mycophenolate mofetil<br>* 1.5 to 2.0 g daily PO BID<br>* Other names: CellCept;Drug: CNI (50%)<br>* 50% reduction from BL<br>|
| Experimental: MMF, ≥75% CNI Reduction<br>Participants received MMF, 1.5 to 2.0 g daily, PO, BID from BL to Week 52. Participants also received a 75% reduced dose of CNI from BL to Week 52. | Drug: Mycophenolate mofetil<br>* 1.5 to 2.0 g daily PO BID<br>* Other names: CellCept;Drug: CNI (≥75%)<br>* ≥75% reduction from BL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Decrease in Glomerular Filtration Rate (GFR) of Greater Than 20% | The percentage of participants with a greater than 20% decrease of GFR during the 1-year period following regimen adjustment. Cockcroft and Gault formula was used for calculated creatinine clearance. | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Graft Loss or Death at Week 52 | Graft loss was defined for this protocol as re-transplantion or death. | Week 52 | 
| Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR) at Week 52 | BPAR was graded according to Banff criteria. | Week 52 | 
| Changes From Baseline in Creatinine Clearance (Milliliters Per Minute [mL/Min]) | Creatinine clearance calculated using the Cockcroft and Gault formula: For adult males, creatinine clearance in mL/min equaled (=) [(140 minus (-) age in years) multiplied by (*) (weight in kilograms (kg)] divided by [72 * serum creatinine in milligrams per deciliter (mg/dL)]. For adult females, creatinine clearance in mL/min = 0.85 * [(140 - age in years) * (weight in kg)] divided by (72 * serum creatinine in mg/dL). | Baseline and Weeks 16, 28, and 40 | 
| Change From Baseline in Corrected Creatinine Clearance (mL/Min) at Week 52 | Corrected creatinine clearance was calculated using the Cockcroft and Gault formula: For adult males, creatinine clearance in mL/min = [(140 - age in years) * (weight in kg] divided by [72 * serum creatinine in mg/dL]. For adult females, creatinine clearance in mL/min = 0.85 * [(140 - age in years) * (weight in kg)] divided by (72 * serum creatinine in mg/dL). | Week 52 | 
| Percentage Change in Creatinine Clearance From Baseline | Creatinine clearance was calculated using the Cockcroft and Gault formula. | Weeks 16, 28, 40, and 52 | 
| Percentage of Participants Experiencing Acute Rejection, Graft Loss, Death, or a Decrease From BL in Creatinine Clearance of ≥20% at Week 52 | The percentage of participants who experienced at least 1 of the following: a ≥20% decrease from BL in creatinine clearance, acute rejection, graft loss, or death 1 year after randomization. | Week 52 |