Comparison of a Tacrolimus Hexal® Based Regimen Versus a Prograf® Based Regimen in de Novo Renal Transplant Recipients

Study Overview
=================
Brief Summary
-----------------
The purpose of this study was to investigate if Tacrolimus Hexal® has similar pharmacokinetic properties compared to Prograf® in de novo renal transplant patients and whether the comparable exposure resulted in similar renal function.

Detailed Description
-----------------
In Phase II of this study there was a high patient drop-out rate and an associated long recruitment timespan. Eighty-one patients were recruited to Phase I and only 45 of the required 54 patients were available for PK analysis. To complete Phase II, 245 (in addition to 81) patients were to be required to achieve calculated sample size. Therefore the protocol was amended to stop recruitment and analyze Phase I patient data of CERL080ADE27 (PK-Phase I). Patients that were still ongoing were scheduled for an end of study (EOS) visit. During this visit patients were informed by the investigator about the end of study and advised about further treatment course.

Official Title
-----------------
Multi-center, Open-label, Prospective, Randomized, Parallel Group Study Investigating a Tacrolimus Hexal® Based Regimen Versus a Prograf® Based Regimen in de Novo Renal Transplant Recipients

Conditions
-----------------
Pharmacokinetics Study in de Novo Kidney Transplantation

Intervention / Treatment
-----------------
* Drug: Prograf
* Drug: Tacrolimus Hexal


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion: primary or sec. kidney transplanted patiens, written consent, cold ischemia < 24 h Exclusion: multi organ, immunological risc pts., PRA >20%, Antibodys against HLA-type of donor organ, hypersensitivity against Tacro or MMF, Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prograf<br>Control therapy: one capsule containing 0.5 mg, 1mg or 5mg Prograf®, one tablet containing 180mg or 360mg Myfortic®, corticosteroids and one vial containing 20mg lyophilisate Simulect® | Drug: Prograf<br>* Prograf® capsules were supplied as capsules of 0.5 mg, 1 mg and 1.5 mg dose strengths.<br>|
| Experimental: Tacroliums Hexal<br>Investigational therapy: one capsule containing 0.5mg, 1mg or 5mg Tacrolimus Hexal®, one tablet containing 180mg or 360mg Myfortic®, corticosteroids and one vial containing 20mg lyophilisate Simulect® | Drug: Tacrolimus Hexal<br>* Tacrolimus Hexal® capsules were supplied to the investigators at dose strengths of 0.5 mg, 1 mg and 1.5 mg.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ANCOVA Model for Change in Nankivell GFR (mL/Min) at Month 6, Without Replacement of Missing Values (Full Analysis Set) | Change in Nankivell glomerular filtration rate (GFR) from baseline to 6 months Glomerular Filtration Rate (GFR): The GFR is the best clinical estimate of renal function in health and disease, and correlates well with the clinical severity of renal function disturbances. Several studies have shown that in patients with progressive renal disease, GFR declines or reciprocal serum creatinine levels elevate linearly over time in a predictable manner. With the help of the serum creatinine values, the GFR was calculated via Nankivell formula. | baseline to month 6 | 
| ANOVA for Dose-normalized Tacrolimus 12-h-AUC (h/103*L) at Month 1 | Compares the PK of Tacrolimus Hexal® assessed by the ratio of the AUC0-12h over one month period post transplantation vs. Prograf® in renal transplant patients | end of month 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Incidence of Biopsy-proven Acute Rejection (BPAR), Graft Loss and Death Until Month 12 (Full Analysis Set) (Full Analysis Set) | The key secondary objective was to assess the incidence of individual endpoints BPAR, graft loss and death until month 6 post-transplantation. | baseline to month 12 | 
| ANCOVA Model for Change in CKD-EPI GFR (Chronic Kidney Disease Epidemiology Collaboration Glomerular Filtration Rate) at Month 6 Post-transplantation | ANCOVA model for change in CKD-EPI Glomerular Filtration Rate (GFR)[ml/min] without replacement of missing values | baseline to Month 6 | 
| ANCOVA Model for Change in MDRD GFR (ml/Min) at Month 6, Without Replacement of Missing Values | MDRD GFR | least square (LS) mean change from baseline to Month 6 | 
| ANCOVA Model for Change in Cockcroft-Gault GFR (ml/Min) at Month 6, Without Replacement of Missing Values | change in Cockcroft-Gault GFR | least square (LS) mean change from baseline to Month 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
GFR, Pharmacokinetics Study, Tacroliums, kidney, transplant rejection, allograft rejection, xenograft rejection, host vs graft disease, renal transplant