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

Renal Transplantation Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00369278
• Other study ID #: CERL080ADE12
• Status: Completed
• Phase: Phase 3
• First received: August 25, 2006
• Last updated: March 25, 2011
• Start date: June 2006
• Est. completion date: December 2008

Study information

• Verified date: March 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Completed
• Enrollment: 128
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion criteria

1. Recipients of de novo cadaveric, living unrelated or living related kidney transplants

2. 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.

3. Patients who are willing and able to participate in the study and from whom written informed consent has been obtained.

Exclusion criteria

1. More than one previous renal transplantation

2. Graft loss due to immunological reasons in the first year after transplantation (in case of secondary transplantation)

3. Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any other organ, different from kidney

4. Patients receiving a kidney from a non-heart beating donor

5. Patients who are recipients of A-B-O incompatible transplants

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Renal Transplantation

Intervention

Drug:
• Enteric-coated mycophenolate sodium (EC-MPS)
Tablets for oral administration

Locations

Country	Name	City	State
Germany	Novartis Investigational Site	Various Cities

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	6 months	No
Secondary	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	6 months	No
Secondary	Renal Function as Measured by Serum Creatinine		6 months	No
Secondary	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	No