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

Phase 4

Completed

• Conditions: Liver Transplantation
• Interventions: Drug: Mycophenolate mofetil; Drug: CNI (50%); Drug: CNI (≥75%)

• Registration Number: NCT00717314
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-05
• Study First Submitted: 2008-07-16
• Study First Submitted QC: 2008-07-16
• Study First Posted: 2008-07-17
• Primary Completion: 2011-07
• Study Completion: 2011-07
• Results First Submitted: 2014-06-04
• Status Verified: 2014-09
• Results First Submitted QC: 2014-09-23
• Last Update Submitted: 2014-09-23
• Results First Posted: 2014-09-29
• Last Update Posted: 2014-09-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 87

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MMF, 50% CNI Reduction	CNI (50%)	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.
MMF, ≥75% CNI Reduction	CNI (≥75%)	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.
MMF, ≥75% CNI Reduction	Mycophenolate mofetil	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.
MMF, 50% CNI Reduction	Mycophenolate mofetil	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Decrease in Glomerular Filtration Rate (GFR) of Greater Than 20%	Week 52	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Graft Loss or Death at Week 52	Week 52	Graft loss was defined for this protocol as re-transplantion or death.
Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR) at Week 52	Week 52	BPAR was graded according to Banff criteria.
Changes From Baseline in Creatinine Clearance (Milliliters Per Minute [mL/Min])	Baseline and Weeks 16, 28, and 40	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).
Change From Baseline in Corrected Creatinine Clearance (mL/Min) at Week 52	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).
Percentage Change in Creatinine Clearance From Baseline	Weeks 16, 28, 40, and 52	Creatinine clearance was calculated using the Cockcroft and Gault formula.
Percentage of Participants Experiencing Acute Rejection, Graft Loss, Death, or a Decrease From BL in Creatinine Clearance of ≥20% at Week 52	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.