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

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

Detailed Description
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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).

Official Title
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Pharmacokinetic Cross-over Study to Evaluate the Influence of Pantoprazole on MPA Bioavailability Administered as Mycophenolate Mofetil and Enteric Coated Mycophenolate Sodium in Maintenance Renal Transplant Patients

Conditions
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Transplantation, Immunosuppression, Drug Interaction

Intervention / Treatment
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* Drug: Mycophenolate sodium
* Drug: Pantoprazole
* Drug: Mycophenolate mofetil


Participation Criteria
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Eligibility Criteria
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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)

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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Mycophenolate mofetil (C)<br>Mycophenolate mofetil (C) b.i.d. every 12 hours for 2 weeks. | Drug: Mycophenolate mofetil<br>* Daily dose: 1000mg, 1500mg, 2000mg. Application alone or with Pantozol® .<br>* Other names: Cellcept®;|
| Other: Mycophenolate mofetil+Pantoprazole (C+P)<br>Mycophenolate mofetil b.i.d and Pantoprazole o.m. for 2 weeks. | Drug: Pantoprazole<br>* Daily dose: 40mg. Application together with CellCept® or Myfortic® .<br>* Other names: Pantozol®;Drug: Mycophenolate mofetil<br>* Daily dose: 1000mg, 1500mg, 2000mg. Application alone or with Pantozol® .<br>* Other names: Cellcept®;|
| Other: Mycophenolate sodium (M)<br>Mycophenolate sodium (M) b.i.d. every 12 hours for 2 weeks. | Drug: Mycophenolate sodium<br>* Daily dose: 720mg, 1080mg, 1440mg. Application alone or together with Pantozol®.<br>* Other names: Myfortic®;|
| Other: Mycophenolate sodium+Pantoprazole (M+P)<br>Mycophenolate mofetil b.i.d and Pantoprazole 40mg o.m. for 2 weeks. | Drug: Mycophenolate sodium<br>* Daily dose: 720mg, 1080mg, 1440mg. Application alone or together with Pantozol®.<br>* Other names: Myfortic®;Drug: Pantoprazole<br>* Daily dose: 40mg. Application together with CellCept® or Myfortic® .<br>* Other names: Pantozol®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-normalized AUC of Mycophenolic Acid | 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. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunosuppressive medication, mycophenolic acid, interaction, proton pump inhibitor, pantoprazole, renal transplant patients, pharmacokinetics, pharmacodynamics, bioavailability