Clinical trial NCT00443937: Pharmacokinetics of Everolimus and Enteric-Coated Mycophenolatesodium Before and After Withdrawal of Cyclosporine in Renal Transplant Patients
Official title: Pharmacokinetics of Everolimus and Enteric-Coated Mycophenolatesodium Before and After Withdrawal of Cyclosporine in Stable Renal Transplant Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Renal Transplantation
Keywords: Kidney Transplantation
Renal Transplantation
Mycophenolate
Cyclosporine
Everolimus
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2007-03-07
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: 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
timeFrame: 7 days
measure: Everolimus trough level will be measured at day 7, 14, 21, 28 and month 2, 4, 6, 9, 12
timeFrame: 1 year
Secondary outcomes:
measure: Safety and tolerability of the treatment regimen consisting over a one year period
timeFrame: 1 year
measure: Renal function during the course of the trial, especially after CNI withdrawal.
timeFrame: 1 year
measure: Routine laboratory parameters during the course of the trial.
timeFrame: 1 year
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité-Universitätsmedizin
Study officials:
affiliation: Charite University, Berlin, Germany
name: Klemens Budde, Prof.
role: PRINCIPAL_INVESTIGATOR
References: