renal transplantation MedDRA version: 18.0 Level: LLT Classification code 10050436 Term: Prophylaxis against renal transplant rejection System Organ Class: 100000004865
Conditions
Interventions
Trade Name: Tacrolimus Hexal Hartkapseln
Pharmaceutical Form: Capsule, hard
CAS Number: 109581-93-3
Other descriptive name: TACROLIMUS MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration typ
Sponsors
Novartis Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female renal allograft recipients aged between 18 and 64 years 2. Patients who have received a primary or secondary kidney transplant from a de novo deceased, living unrelated or living related donor aged =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any other organ, different from kidney 2. Graft loss due to immunological reasons in the first year after transplantation (in case of secondary transplantation) 3. Patients receiving a kidney from a non-heart beating donor 4. Patients who are recipients of A-B-O incompatible transplants 5. Patients with a current Panel Reactive Antibody (PRA) level of > 20% PRA levels within 4 months prior to enrollment are acceptable 6. Patients with already existing antibodies against the HLA-type of the receiving transplant (in the knowledge of the investigator at the time point of transplantation) 7. Patients with any known hypersensitivity to tacrolimus or mycophenolic acid, to drugs with similar chemical structures or other components of the formulations (e.g. lactose, see also SmPCs) 8. Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer 9. Patients with thrombocytopenia (platelets 3 times UNL). Viral serology results obtained within 6 months prior to enrollment are acceptable 15. Evidence of severe liver disease (incl. abnormal liver enzyme profile, i.e. AST or ALT > 3 times UNL) 16. Evidence of drug or alcohol abuse 17. Patients, who have already been randomized into this trial earlier must not be included a second time. 18. Women o who are pregnant or breast feeding (pregnancy defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/ml)) o who are menstruating and capable of becoming pregnant* and not practicing a medically approved method of contraception (Pearl Index 40 mIU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy **examples of particularly reliable methods with Pearl Index (PI) <1, according to guidelines of Deutsche Gesellschaft für Gynäkologie und Geburtshilfe: ? Combination pill with estrogen and gestagen (no mini-pill, PI=0.1-0.9) ? Vaginal ring (PI=0.65 uncorr.; 0.4 corr.) ? Contraceptive patch (PI= 0.72 uncorr.; 0.9 corr.) ? Estrogen-free ovulation inhibitors (PI=0.14) ? Progestin-containing contraceptives (PI=0-0.08) ? Injectable 3-month depot progestins (PI=0.3-1.4; 0.88 corr.) ? Intra-uterine progestine device (PI=0.16) ? Total abstinence (when this is in line with the preferred and usual lifest
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: PHASE I: To demonstrate that the pharmacokinetics of Tacrolimus Hexal® assessed by the ratio of the AUC0-12h over a one month period post-transplantation is comparable to Prograf® in renal transplant patients. PHASE II (including the patients enrolled in Phase I, Phase II study will not be conducted): To demonstrate non-inferiority in renal function assessed by glomerular filtration rate (Nankivell formula) between both treatment arms at month 6 post-transplantation in renal transplant patients.;Secondary Objective: Phase I: ? To compare bioavailability of Tacrolimus Hexal® to Prograf® using the dose-normalized AUC0-12h at Day 3, Day 10 and Month 1. ? To compare pharmacokinetics of Tacrolimus Hexal® to Prograf® assessed by the ratio of the AUC0-4h at Month 3 and Month 6. ? To compare the ratio of cmax of Tacrolimus Hexal® to Prograf® over a one month period after transplantation. ? To compare the c0 Tacrolimus Hexal® to Prograf® at Day 3, Day 10, Month 1, Month 3 and Month 6. Phase II (including the patients enrolled in Phase I, Phase II study will not be conducted): The key secondary objective of Phase II is to assess the incidence of treatment failure (defined as biopsy-proven acute rejection [BPAR], graft loss or death) between the two arms at month 6 post-transplantation.;Primary end point(s): This study has two phases with primary objectives each: The primary objective of phase I of this study is to evaluate whether a generic Tacrolimus-based immunosuppressive regimen has similar pharmacokinetics as a Prograf®-based immunosuppressive regimen, as measured by dose-normalized AUC0-12h over a one month period after transplantation. Note: The analysis of this primary objective will be described in Section 10.6.1(Pharmacokinetics). The primary objective of phase II of this study is to demonstrate that a generic Tacrolimus-based immunosuppressive regimen has non-inferior efficacy compared with a Prograf®-based immunosuppressive regimen on renal fun | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? To assess renal function by glomerular filtration rate (CKD-EPI, Cockcroft-Gault and MDRD method). ? To assess the incidence of BPAR, graft loss and death. ? To assess safety and tolerability during the study. | — |
Countries
Germany
Contacts
Public ContactProject Leader
Novartis Pharma GmbH
Outcome results
None listed