Extension Study to Evaluate the Long-term Efficacy and Safety of Everolimus in Liver Transplant Recipients
Condition: Liver Transplant Recipient
Intervention: Tacrolimus (reduced tacrolimus); Everolimus (reduced tacrolimus); Tacrolimus (tacrolimus elimination); Everolimus (tacrolimus elimination); Tacrolimus (tacrolimus control); Corticosteroids
Intervention description: After everolimus whole blood trough levels were confirmed to be in the target range of 3-8 ng/mL, tacrolimus tapering began, achieving a target tacrolimus whole blood trough level of 3-5 ng/mL by 3 weeks after randomization, a level which was maintained for the duration of the study.; Everolimus was started within 24 hours of randomization at a dose of 1.0 mg twice a day (bid, 2 mg daily dose). The dose was adjusted to maintain everolimus trough blood levels between 3-8 ng/mL for the duration of the study.; After everolimus whole blood trough levels were confirmed to be in the target range of 3-8 ng/mL, tacrolimus tapering began, achieving a target tacrolimus whole blood trough level of 3-5 ng/mL by 3 weeks after randomization. Tacrolimus elimination was started beginning at Month 4. Tacrolimus was tapered after everolimus whole blood trough levels were within the target range of 6-10 ng/mL. Tacrolimus was completely eliminated by the end of Month 4.; Everolimus was started within 24 hours of randomization at a dose of 1.0 mg twice a day (bid, 2 mg daily dose). The dose was adjusted to maintain everolimus trough blood levels between 3-8 ng/mL until Month 4; beginning with Month 4, the dose was adjusted to maintain everolimus trough blood levels between 6-10 ng/mL.; Tacrolimus trough levels were targeted to be maintained at 8-12 ng/mL until Month 4. At Month 4, tacrolimus whole blood trough levels were decreased to a target trough level of 6-10 ng/mL for the remainder of the study.; For patients in all groups, corticosteroids were initiated at or prior to the time of transplantation according to local practice. Corticosteroids could be used for the duration of the study but could not be eliminated before Month 6. The corticosteroids were not specified in the protocol because they were adminsitered to the participants according to local practice as part of standard of care.
Intervention MeSH terms: Everolimus; Tacrolimus
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 284.0
Sex: All
Minimum age: 20 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Liver transplantation; Everolimus; Calcineurin inhibitors; Tacrolimus; Renal function; Progression of HCV related allograft fibrosis

Summary:

      The reason for this extension is to evaluate the long-term safety and efficacy of two
      concentration-controlled everolimus regimen in de novo liver transplant recipients. The most
      important long-term safety assessments include evaluation of renal function, progression of
      HCV related allograft fibrosis, and other treatment related effects at Month 36
      post-transplantation compared to extension baseline (Months 24 post-transplantation).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent

          -  Ability and willingness to adhere to study regimen

          -  Completed core study with assigned regimen;

        Exclusion Criteria:

        Patients fulfilling any of the following criteria are not eligible for inclusion in this
        study:

          -  Severe hypercholesterolemia or hypertriglyceridemia.

          -  Low platelet count.

          -  Low white blood cell count.

          -  Positive test for human immunodeficiency virus (HIV).

          -  Systemic infection requiring active use of IV antibiotics.

          -  Patients in a critical care setting.

          -  Use of prohibited medication.

          -  Use of immunosuppressive agents not utilized in the protocol.

          -  Hypersensitivity to any of the study drugs or similar drugs.

          -  Pregnant or nursing (lactating) women

          -  Women of child-bearing potential not using a highly effective method of birth control.

        Other protocol-defined inclusion/exclusion criteria may apply