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

Phase 3

Completed

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).

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Intensified Mycophenolate sodium	Enteric-coated mycophenolate sodium (EC-MPS)	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.
Standard Mycophenolate sodium	Enteric-coated mycophenolate sodium (EC-MPS)	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.

Primary Outcome Measures

Name	Time	Method
Time to First Occurrence of a Mycophenolic Acid (MPA) Plasma Concentration of ≥ 40 mg*h/L	Assessed on day 3, 10, 21, 42, 56 and 84	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.
Time to First Occurrence of Any Treatment Failure During the First 6 Months Post-treatment or at Month 6 Post-treatment	6 months	Median time to first occurrence of treatment failure was not reached in this study.
Number of Participants With Any Treatment Failure	6 months	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Single Treatment Failures	6 months	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.)
Rates of Events for Treated Acute Rejection, Death, Graft Loss, or Loss to Follow up on Day 28, Day 84, and Day 180	6 months	Due to a small number of events, median time to \<event\> was not reached.
Time to "Event" for the Composite Endpoint as Well as All Individual Components of That Endpoint "Treatment Failure" Including Clinical Rejections	6 months	Due to a small number of events, median time to \<event\> was not reached.
Renal Function as Measured by Serum Creatinine	6 months
Renal Function as Measured by Glomerular Filtration Rate (GFR)	6 months	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.