A Pharmacokinetic Study of CellCept (Mycophenolate Mofetil) Versus Mycophenolate Sodium in Kidney Transplant Patients

Study Overview
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Brief Summary
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This open-label, 2-arm study will compare the pharmacokinetics of CellCept and mycophenolate sodium in kidney transplanted patients on a calcineurininhibitor-free mycophenolic acid-based therapy. On the study day patients will take their prescribed medication (either CellCept or mycophenolate sodium). Blood samples will be drawn directly before and at intervals up to 12 hours after intake of the study medication. Anticipated time on study treatment is 12 hours and target sample size is 24.

Official Title
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Comparison of Pharmocokinetics of Mycophenolate Mofetil and Enteric Coated Mycophenolate Sodium in Calcineurininhibitor-free Treated Patients After Renal Transplantation

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: MMF
* Drug: EC-MPS
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >/=18 years of age kidney transplantation >/=6 months ago on mycophenolic acid-based, calcineurininhibitor-free therapy for >/=3 months, >/=1 month on stable dose co-therapy with 5mg prednisone for >/=1 month Exclusion Criteria: active gastrointestinal ulcus severe diarrhea od gastrointestinal disease severe impairment of renal function current malignancy Lesch-Nyhan- or Kelley-Seegmiller-Syndrome

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MMF, Prednisone<br>Participants received mycophenolate mofetil (MMF) orally (PO) at a dose of 1 gram per day (g/day) twice daily (BID), and prednisone, PO, up to 5 milligrams per day (mg/day) for at least 1 month. | Drug: MMF<br>* 1 g per day b.i.d. p.o. for at least 1 month<br>* Other names: mycophenolate mofetil;Drug: Prednisone<br>* 5 mg per day p.o.<br>|
| Active Comparator: EC-MPS<br>Participants received mycophenolate sodium (EC-MPS), PO, at a dose of 720 mg/day BID, and prednisone PO up to 5 mg/day for at least 1 month. | Drug: EC-MPS<br>* 720 mg b.i.d. p.o. for at least 1 month<br>* Other names: mycophenolate sodium;Drug: Prednisone<br>* 5 mg per day p.o.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pre-dose Trough Concentration (C0) | The mean mycophenolic acid (MPA) concentration in plasma was determined (in milligrams per liter [mg/L]) from blood samples collected predose (immediately before receiving study treatment). | Day 1 predose | 
| Dose-Normalized C0 | Dose normalized C0 was determined (in mg/L) from blood samples collected predose. Both MMF and EC-MPS doses were normalized to a standard dose of 1 g MMF or 720 mg EC-MPS, respectively. The dose normalization was calculated as follows: For the MMF group: Dose normalized C0 equals (=) C0 divided by (/) (actual dose taken/1000) For the EC-MPS group: Dose normalized C0 = C0 / (actual dose taken/720) | Day 1 predose | 
| Minimum Plasma Concentration (Cmin) | The mean minimum MPA concentration in plasma was determined (in mg/L) from blood samples collected predose and postdose on Day 1. | Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours | 
| Dose-Normalized Cmin | Dose-normalized Cmin was determined (in mg/L) from blood samples collected predose and postdose. Both MMF and EC-MPS doses were normalized to a standard dose of 1 g MMF or 720 mg EC-MPS, respectively. The dose normalization was calculated as follows: For the MMF group: Dose normalized Cmin = Cmin/ (actual dose taken/1000) For the EC-MPS group: Dose normalized Cmin = Cmin / (actual dose taken/720) | Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours | 
| Maximum Plasma Concentration (Cmax) | The mean maximum MPA concentration in plasma was determined (in mg/L) in blood samples collected predose and postdose on Day 1. | Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours | 
| Dose-Normalized Cmax (mg/L) | Dose-normalized Cmax in plasma was determined (in mg/L) from blood samples collected predose and postdose on Day 1. Both MMF and EC-MPS doses were normalized to a standard dose of 1 g MMF or 720 mg EC-MPS, respectively. The dose normalization was calculated as follows: For the MMF group: Dose normalized Cmax = Cmax / (actual dose taken/1000) For the EC-MPS group: Dose normalized Cmax = Cmax / (actual dose taken/720) | Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours | 
| MPA Area Under the Curve From 0 to 12 Hours (AUC0-12) | The mean MPA AUC0-12 in plasma was determined (in mg multiplied by hours, per Liter [mg*h/L]) from blood samples collected predose and postdose on Day 1. | Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours | 
| Dose-Normalized MPA AUC0-12 | Dose-normalized MPA AUC0-12 in plasma was determined (mg*h/L) from blood samples collected predose and postdose on Day 1. Both MMF and EC-MPS doses were normalized to a standard dose of 1 g MMF or 720 mg EC-MPS, respectively. The dose normalization was calculated as follows: For the MMF group: Dose normalized MPA AUC = MPA AUC / (actual dose taken/1000) For the EC-MPS group: Dose normalized MPA AUC = MPA AUC / (actual dose taken/720) | Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours | 
| Percentage of Participants By Time to Maximum Plasma Concentration (Tmax) |  | Day 1 predose and postdose at 30 and 60 minutes and 2, 3, 4, 5, 6, 8 10 and 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regression Coefficients For Participants Receiving MMF | The estimated regression coefficients for participants who received MMF presented in milligrams per liter (mg/L). | Day 1 at 30 minutes and 1 and 2 hours postdose |