Efficacy and Safety of Concentration-controlled Everolimus to Eliminate or to Reduce Tacrolimus Compared to Tacrolimus in de Novo Liver Transplant Recipients

This 24-month study consisted of a screening period, a baseline period (3 to 7 days post-transplantation) followed by a run-in period that ended on the day of randomization at 30 days (± 5 days) post-transplantation. Patients were screened for eligibility prior to liver transplantation. Patients who had undergone successful liver transplantation were initiated on a tacrolimus-based regimen that included corticosteroids and entered the baseline period (between 3 and 7 days post-transplantation). At 30 (± 5) days post-transplantation, patients who met additional randomization inclusion/exclusion criteria were randomized into the study.

Inclusion criteria

• Ability and willingness to provide written informed consent and adhere to study regimen.
• Recipients who are 18-70 years of age of a primary liver transplant from a deceased donor.
• Recipients who have been initiated on an immunosuppressive regimen that contains corticosteroids and tacrolimus, 3-7 days post-transplantation.
• Confirmed recipient hepatitis C virus (HCV) status at Screening (either by antibody or by PCR (polymerase chain reaction).
• Allograft is functioning at an acceptable level by the time of randomization as defined by protocol specific laboratory values.
• Abbreviated Modification of Diet in Renal Disease estimated glomerular filtration rate (MDRD eGFR) ≥ 30 mL/min/1.73m2. Results obtained within 5 days prior to randomization are acceptable, however, no sooner than Day 25 post-transplantation.
• Verification of at least 1 tacrolimus trough level of ≥ 8 ng/mL in the week prior to randomization. Investigators should make adjustments in tacrolimus dosing to continue to target trough levels above 8 ng/mL prior to randomization.

Exclusion criteria

• Patients who are recipients of multiple solid organ or islet cell tissue transplants, or have previously received an organ or tissue transplant. Patients who have a combined liver-kidney transplant.
• Recipients of a liver from a living donor, or of a split liver.
• History of malignancy of any organ system within the past 5 years whether or not there is evidence of local recurrence or metastases, other than non-metastatic basal or squamous cell carcinoma of the skin, or HCC (hepatocellular carcinoma) (see next criteria).
• Hepatocellular carcinoma that does not fulfill Milan criteria (1 nodule ≤ 5 cm, 2-3 nodules all < 3 cm) at the time of transplantation as per explant histology of the recipient liver.
• Any use of antibody induction therapy.
• Patients with a known hypersensitivity to the drugs used on study or their class, or to any of the excipients.
• Patients who are recipients of ABO incompatible transplant grafts.
• Recipients of organs from donors who test positive for Hepatitis B surface antigen or HIV are excluded.
• Patients who have any surgical or medical condition, which in the opinion of the investigator, might significantly alter the absorption, distribution, metabolism and excretion of study drug.
• Women of child-bearing potential (WOCBP).
• Patients with any history of coagulopathy or medical condition requiring long-term anticoagulation which would preclude liver biopsy after transplantation. (Low dose aspirin treatment or interruption of chronic anticoagulant is allowed).

Other protocol-defined inclusion/exclusion criteria may apply.