This study is designed to provide efficacy and safety data for everolimus in de novo renal
transplant recipients in order to gain regulatory approval to make everolimus available for
clinical use in Japan.
This study is designed to evaluate the efficacy and safety comparing
concentration-controlled everolimus (1. 5 mg/day starting dose) with reduced dose Neoral®
(RDN) and corticosteroids versus 2 g/day mycophenolate mofetil (MMF) with standard dose
Neoral® (SDN) and corticosteroids in de novo renal transplant recipients.
Inclusion Criteria:
- Male or female de novo renal transplant recipients between 18 and 65 years of age
- Patients who are receiving a primary cadaveric donor or non-HLA identical living
donor kidney transplant
- Patients who have given written informed consent to participate in the study
- Females capable of becoming pregnant must have a negative pregnancy test prior to
randomization.
Exclusion Criteria:
- Patients with no evidence of graft function within 24 hours of transplantation are
excluded
- Recipients of dual kidney transplants
- Patients who are recipients of multiple solid organ or tissue transplants, or have
previously received an organ or tissue transplant.
- Recipients of kidneys from HLA-identical living related donors
- Patients who are recipients of ABO incompatible transplants or T cell crossmatch
positive transplant. Although Panel Reactive Antibodies (PRA) test is not mandatory,
patients whose most recent anti-HLA Class I PRA >20% By a CDC-(Complement dependent
cytotoxicity) based assay or >50% by a Flow Cytometry or ELISA (Enzyme linked
immunosorbent assay) - based assay
- Patients who have tested positive for HIV, HCV, or Hepatitis B surface antigen.
Laboratory results obtained within 6 months prior to randomization are acceptable,
otherwise these tests should be performed within two weeks prior to randomization.
- Recipients of organs from donors who test positive for Hepatitis B surface antigen,
HCV or HIV are excluded
- Donor organ with a cold ischemia time >24 hours
- Donor age greater than 65 years
- Patients with platelet count <100,000/mm at baseline before transplantation
- Patients with an absolute neutrophil count of < 1,500/mm³ or white blood cell count
of < 4,500/mm³ at baseline before transplantation
- Patients who have severe hypercholesterolemia (>350 mg/dL; >9 mmol/L) or
hypertriglyceridemia (>500 mg/dL; >8. 5 mmol/L). Patients with controlled
hyperlipidemia are acceptable
- Patients who have an abnormal liver profile such as ALT, AST, ALP or total bilirubin
>3 times the ULN
- Patients with a known hypersensitivity to either of the study drugs or their class,
or to any of the excipients
- Patients who are treated with drugs that are strong inducers or inhibitors of
cytochrome P450
- Patients who are unable to take oral medication at time of randomization
- Patients who received an investigational drug or who have been treated with a
non-protocol immunosuppressive drug or treatment within 30 days or 5 half-lives prior
to randomization
- Patients with a history of malignancy of any organ system, treated or untreated,
within the past 5 years whether or not there is evidence of local recurrence or
metastases, with the exception of localized excised non-melanomatous skin lesions
- Patients with clinically significant systemic infection at time of transplant or
within two weeks prior to transplant
- Patients with a history of severe diarrhea, active peptic ulcer disease, or
uncontrolled diabetes mellitus
- Patients who have cardiac failure at time of screening (resting dyspnea, with Grade ≥
3 according to Old New York Heart Association Classification (Appendix 7) or any
severe cardiac disease as determined by the investigator
- 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 medication
- Patients with abnormal physical or laboratory findings of clinical significance
within 2 weeks prior to randomization which would interfere with the objectives of
the study
- Patients with any history of coagulopathy or medical condition requiring long-term
anticoagulation which would preclude renal biopsy after transplantation. (Low dose
aspirin treatment or interruption of chronic anticoagulant is allowed)
- Females of childbearing potential who are planning to become pregnant, who are
pregnant and/or lactating, who are unwilling to use effective means of contraception.
- Other protocol-defined inclusion/exclusion criteria may apply
