Pharmacokinetics of Everolimus and Enteric-Coated Mycophenolatesodium Before and After Withdrawal of Cyclosporine in Renal Transplant Patients

Study Overview
=================
Brief Summary
-----------------
Cyclosporine (CNI), a potent immunosuppressive drug used in transplant recipients to prevent graft rejection, can cause renal impairment in some patients. The aims of this study are To determine the influence of CNI discontinuation on the drug exposure and key pharmacokinetic parameters of everolimus and enteric-coated mycophenolate sodium (EC-MPS) To determine the adequate dosing of everolimus and EC-MPS in a CNI-free regimen To investigate the CNI-free regimen with EC-MPS and everolimus with respect to safety (e.g. rejection rates) and tolerability To investigate renal function after CsA withdrawal

Official Title
-----------------
Pharmacokinetics of Everolimus and Enteric-Coated Mycophenolatesodium Before and After Withdrawal of Cyclosporine in Stable Renal Transplant Patients

Conditions
-----------------
Renal Transplantation

Intervention / Treatment
-----------------
* Drug: enteric-coated mycophenolate sodium
* Drug: everolimus


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients having a kidney transplant since at least 6 months but for no longer than 5 years. Patients in a stable condition in terms of graft function Patients currently receiving EC-MPS and CsA with or without corticosteroids as part of their immunosuppressive regimen for at least 1 month prior to Baseline Females of childbearing potential must have a negative serum pregnancy test prior to study inclusion. If positive, the patient will not be enrolled. Effective contraception must be used during the trial. Exclusion Criteria: Patients with any known hypersensitivity to EC-MPS or everolimus or other components of the formulation (e.g., lactose) Patients with a history of severe rejection (according to BANFF criteria) within 3 months of enrollment in this trial. Changes to the immunosuppressive regimen during the last 3 months due to immunologic reasons. Patients with thrombocytopenia (platelets <100,000/mm3), with an absolute neutrophil count of <1,500/mm3 and/or leukocytopenia (leukocytes <4,500/mm3), and/or hemoglobin <9.0 g/dL at baseline. Patients with proteinuria at baseline (> 1g/d) Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: enteric-coated mycophenolate sodium|oral|
|Drug: everolimus|oral|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Kinetic Profiles (MPA, everolimus, and optional IMPDH) will be measured at day 0, 7 and 7 days after complete removal of CsA and last dose adjustment of everolimus due to trough level outside target range |  | 7 days | 
| Everolimus trough level will be measured at day 7, 14, 21, 28 and month 2, 4, 6, 9, 12 |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of the treatment regimen consisting over a one year period |  | 1 year | 
| Renal function during the course of the trial, especially after CNI withdrawal. |  | 1 year | 
| Routine laboratory parameters during the course of the trial. |  | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Kidney Transplantation, Renal Transplantation, Mycophenolate, Cyclosporine, Everolimus