E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prophylaxis against renal transplant rejection
Renal transplant -> immunosuppressant drug therapy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054980 |
E.1.2 | Term | Immunosuppressant drug therapy |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038533 |
E.1.2 | Term | Renal transplant |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050436 |
E.1.2 | Term | Prophylaxis against renal transplant rejection |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Study objectives: The objective of this pharmacokinetic trial is to analyze, whether the concomitant administration of a proton pump inhibitor influences the bioavailability of mycophenolic acid, applied as either mycophenolat mofetil or enteric-coated mycophenolic acid.
Primary objective: Evaluation of the bioavailability (as measured by area-under-the-concentration-curve (AUC)) of mycophenolic acid in stable renal transplant patients under immunosuppressive maintenance therapy after application of CellCept® alone or in combination with pantozol®; myfortic® alone or in combination with pantozol®. |
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E.2.2 | Secondary objectives of the trial |
• Analysis of additional pharmacokinetic parameters, such as maximal concentration (Cmax), average concentration (Cavg), minimal concentration (Cmin), time to Cmax (Tmax), and apparent clearance (CL/F) of mycophenolic acid (MPA), • Analysis of the pharmacokinetic characteristics of the MPA metabolite MPAG, • Analysis of IMPH activity and the related pharmacodynamic (PD) parameters (maximal activity (Emax), minimal activity (Emax), average activity (Aavg), maximal inhibition), • Analysis of the safety and tolerability, in particular analysis of gastrointestinal discomfort (using standardized questionnaires), infections, leukopenia, anemia, thrombocytopenia, liver enzymes (AST, ALT), albumin- and protein content, gastrointestinal AEs incl. intensity, renal function using serum creatinine and GFR (according to Nanikvell and Cockroft-Gault), incidence of biopsy-proven acute rejections, and graft loss.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients who are at least 18 years of age, • Willing to provide informed consent, • Suitable and willing to switch treatment according to the study plan, • Patients who are on stable immunosuppressive pre-treatment for at least one month with Cyclosporin A (C0-level of 75-150 ng/mL or C2-level of 400-900 ng/mL), Myfortic® or Cellcept® with or without corticosteroids , • Renal transplantation, at least 6 months prior to study inclusion, • 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%).
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E.4 | Principal exclusion criteria |
• 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 who are not on stable treatment with enzyme inductors or enzymes for one month before study start, • Patients with renal function <30mL/min (using the Cockroft-Gault formula), • Patients on treatment with clopidogrel, • Acute rejection less than 1 month before study inclusion, • Patients who are HIV positive, HCV positive or HBsAg positive , • Patients with gastrointestinal disorders which could affect resorption, • Pregnancy and/or lactation, • Drug or alcohol abuse in the patient’s history, • (Patients with) insufficient co-operation with the clinical investigator (e.g. suspicion of non-compliance), • Patients with a history of psychological illness or condition such as to interfere with the patient’s ability to understand the requirements, the consequences and possible outcomes of the study and who are not willing to give a valid informed consent to the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Evaluation of the bioavailability (as measured by area-under-the-concentration-curve (AUC)) of mycophenolic acid in stable renal transplant patients under immunosuppressive maintenance therapy after application of CellCept® alone or in combination with pantozol®; myfortic® alone or in combination with pantozol®. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
PR1, PR1+PR3, PR2, PR2+PR3 |
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E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of the trial is the - last patient last visit - as defined in the protocol. A premature termination of the study is not intended. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |