Intensified vs. Standard Dose Therapy With Mycophenolate Sodium Plus Cyclosporin Microemulsion and Corticosteroid Combination in Patients With de Novo Renal Transplant Patients

Study Overview
=================
Brief Summary
-----------------
This study will assess the association of an initially intensified dosing regimen of enteric-coated mycophenolate sodium (EC-MPS) during the first 6 weeks post renal transplantation with acute rejections relative to the rapid achievement of an MPA (mycophenolic acid) exposure of ≥ 40 mg*h/L compared to a standard dosing regimen of EC-MPS. Additionally, this study will assess safety and tolerability of the intensified dosing regimen of EC-MPS. This study will be conducted in 2 stages (Stage I and Stage II).

Official Title
-----------------
Multi-center, Open-label, Prospective, Randomized, Parallel Group Study Investigating an Intensified Enteric-coated Mycophenolate Sodium (EC-MPS) Dosing Regimen in Comparison to a Standard Dosing Regimen of EC-MPS in Combination With Cyclosporin Microemulsion and Corticosteroids in de Novo Renal Transplant Patients

Conditions
-----------------
Renal Transplantation

Intervention / Treatment
-----------------
* Drug: Enteric-coated mycophenolate sodium (EC-MPS)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria Recipients of de novo cadaveric, living unrelated or living related kidney transplants Females capable of becoming pregnant must have a negative serum pregnancy test within 7 days prior to or at baseline, and are required to practice an approved method of birth control for the duration of the study and for a period of 6 weeks following discontinuation of study medication, even where there has been a history of infertility. Patients who are willing and able to participate in the study and from whom written informed consent has been obtained. Exclusion criteria More than one previous renal transplantation Graft loss due to immunological reasons in the first year after transplantation (in case of secondary transplantation) Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any other organ, different from kidney Patients receiving a kidney from a non-heart beating donor Patients who are recipients of A-B-O incompatible transplants Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intensified Mycophenolate sodium<br>Enteric-coated mycophenolate sodium was given according to the following dosing regimen: Day 1-14: 2880 mg/day (2 x 1440 mg), then day 15-42: 2160 mg/day (2 x 1080 mg), then day 43-End of study (month 6): 1440 mg/day (2 x 720 mg). Total duration of treatment was 180 days. | Drug: Enteric-coated mycophenolate sodium (EC-MPS)<br>* Tablets for oral administration<br>* Other names: myfortic;|
| Active Comparator: Standard Mycophenolate sodium<br>Enteric-coated mycophenolate sodium was given according to the following dosing regimen: Day 1 - End of Study(month 6): 1440 mg/day (2 x 720 mg). Total duration of treatment was 6 months. | Drug: Enteric-coated mycophenolate sodium (EC-MPS)<br>* Tablets for oral administration<br>* Other names: myfortic;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Occurrence of a Mycophenolic Acid (MPA) Plasma Concentration of ≥ 40 mg*h/L | Non-compartmental MPA pharmacokinetic parameters were derived from individual plasma concentration-time profiles using WinNonLin 5.2 software. The areas under the curve were calculated by means of the linear trapezoidal rule. | Assessed on day 3, 10, 21, 42, 56 and 84 | 
| Time to First Occurrence of Any Treatment Failure During the First 6 Months Post-treatment or at Month 6 Post-treatment | Median time to first occurrence of treatment failure was not reached in this study. | 6 months | 
| Number of Participants With Any Treatment Failure | Treatment failures were defined as a composite endpoint of biopsy proven acute rejection (BPAR), graft loss, and death, loss to follow up and discontinuations from study drug treatment due to lack of efficacy or toxicity (at least one condition must be present) during the first 6 months or until final assessment. Any participants who were suspected of having acute rejection episodes had biopsies performed to prove whether a rejection had occurred. Graft loss was considered as the day the patient started dialysis and was not able to subsequently be removed or the day of graft nephrectomy. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Single Treatment Failures | Rates for all individual components of the primary endpoint 'treatment failure' until day 180: Acute rejection diagnosed by biopsy (BPAR) graft loss death loss to follow up discontinuation from study drug due to lack of efficacy or toxicity (adverse events, every adverse event had to be interpreted as toxicity) conversion to another dosing regimen (conversion to tacrolimus, prograf, etc.) | 6 months | 
| Rates of Events for Treated Acute Rejection, Death, Graft Loss, or Loss to Follow up on Day 28, Day 84, and Day 180 | Due to a small number of events, median time to <event> was not reached. | 6 months | 
| Time to Event for the Composite Endpoint as Well as All Individual Components of That Endpoint Treatment Failure Including Clinical Rejections | Due to a small number of events, median time to <event> was not reached. | 6 months | 
| Renal Function as Measured by Serum Creatinine |  | 6 months | 
| Renal Function as Measured by Glomerular Filtration Rate (GFR) | The Glomerular Filtration Rate (GFR) was calculated using the following formulas: Cockcroft-Gault formula: calculation using the participant's age, gender, weight, and serum creatinine levels. MDRD formula: calculation using the participant's age, gender, serum creatinine, urea nitrogen, and albumin levels. | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Renal transplantation, mycophenolate