Influence of Pantoprazole on the Bioavailability of MMF and EC-MPS

Phase 4

Completed

Interventions: Drug: Mycophenolate sodium
Drug: Mycophenolate mofetil
Drug: Pantoprazole

Brief Summary: The objective of this pharmacokinetic study is to examine a possible drug-drug interaction of Pantoprazole on the bioavailability mycophenolic acid.

Detailed Description: It is a randomized open-label 4-sequence 4-period pharmacokinetic cross-over study. The objective of the pharmacokinetic study is to examine a drug-drug interaction of pantoprazole on the bioavailability mycophenolic acid administered as either mycophenolate mofetil (Cellcept(R) or mycophenolate Sodium; EC-MPS (Myfortic (R) in stable renal allograft recipients under maintenance immunosuppressive therapy (cyclosporine +/- low dose glucocorticoids).

Recruitment & Eligibility

Inclusion Criteria

patients >18 years old
patients who are on stable immunosuppressive therapy for at least one month with ciclosporin, EC-MPS or MMF +/- corticosteroids
renal transplantation, at least 6 months prior study inclusion
suitable and willing to switch treatment according to the study plan
women of childbearing potential must have a negative serum pregnancy test before study start and effective contraception must be used (method with PEARL index <1%)

Exclusion Criteria

patients with renal function <30ml/min (estimated by Cockcroft Gault formula)
patients who are not on stable treatment with enzyme inductors or enzyme inhibitors for <1 month before study entry
patients who take medication which is known for interfering with MPA absorption for <1 month before study entry
known anamnestic hypersensitivity to one of the investigational products or drugs with similar chemical structure and to other components of the investigational products, respectively
patients on treatment with clopidogrel
acute rejection < 1 month before study inclusion
patients who are HIV positive, hepatitis C virus (HCV) positive, HBsAg positive
patients with gastrointestinal disorders which could affect resorption
pregnancy and/or lactation
drug or alcohol abuse in patient's history
patients with history of psychological illness or condition, which might interfere with the ability to understand the requirements, consequences, possible outcome of the study and patients who are not willing to give valid informed consent
patients with insufficient co-operation with the clinical investigator (e.g. suspicion of non-compliance)

Arm && Interventions

Group	Intervention	Description
Mycophenolate sodium+Pantoprazole (M+P)	Mycophenolate sodium	Mycophenolate mofetil b.i.d and Pantoprazole 40mg o.m. for 2 weeks.
Mycophenolate sodium (M)	Mycophenolate sodium	Mycophenolate sodium (M) b.i.d. every 12 hours for 2 weeks.
Mycophenolate mofetil (C)	Mycophenolate mofetil	Mycophenolate mofetil (C) b.i.d. every 12 hours for 2 weeks.
Mycophenolate mofetil+Pantoprazole (C+P)	Mycophenolate mofetil	Mycophenolate mofetil b.i.d and Pantoprazole o.m. for 2 weeks.
Mycophenolate mofetil+Pantoprazole (C+P)	Pantoprazole	Mycophenolate mofetil b.i.d and Pantoprazole o.m. for 2 weeks.
Mycophenolate sodium+Pantoprazole (M+P)	Pantoprazole	Mycophenolate mofetil b.i.d and Pantoprazole 40mg o.m. for 2 weeks.

Primary Outcome Measures

Name	Time	Method
Dose-normalized AUC of Mycophenolic Acid	Study duration for each patient: 2 months. After 10-14 days of drug intake blood samples for PK/PD analysis will be collected. On the next day new treatment starts. There are 4 study visits at the study center. Duration will be approximately 12hours	Bioavailability (12h AUC) of mycophenolic acid in renal transplant patients after administration of MMF+/-PAN and EC-MPS+/-PAN For evaluation of pharmacokinetic and pharmacodynamic parameters blood will be collected before, 0.5h, 1h, 1.5h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h after drug intake.

Secondary Outcome Measures