Evaluation of the Therapeutic Benefit of an Initial Intensified Dosing Regimen of Mycophenolate Sodium Versus a Standard Regimen in Renal Transplant Patients

A Randomized, Multicenter, Parallel-group, Open-label Study to Evaluate the Therapeutic Benefit of an Initially Intensified Dosing Regimen of Mycophenolate Sodium Versus a Standard Dosing Regimen, in Combination With Cyclosporine and Corticosteroids in de Novo Renal Transplant Patients

The purpose of this study is to determine if an initial intensified enteric-coated mycophenolate sodium (Myfortic) dosing regimen administered during the first six weeks post renal transplantation provides improved efficacy, with a similar safety profile, compared to a standard regimen of Myfortic.

Study Overview

• Status: Completed
• Conditions: Kidney Transplantation
• Intervention / Treatment: Drug: Enteric-coated mycophenolate sodium (Myfortic); Drug: Cyclosporine (Neoral); Drug: Prednisone

• Study Type: Interventional
• Enrollment (Actual): 313
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland
    • Novartis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males or females, 18 to 65 years old
• First or second time kidney transplant patients
• For females capable of becoming pregnant, negative pregnancy test prior to entry into trial and effective birth control during trial and 3 months after stopping trial medication

Exclusion Criteria:

• Previous graft loss due to immunological reasons in the 1st year after the 1st transplant
• Multi-organ recipients or previous transplant of another organ, different from the kidney
• Recipients from a non-heart-beating donor
• Known hypersensitivity to mycophenolic acid or cyclosporine
• HIV positive or Hepatitis B surface antigen positive
• History of malignancy (past 5 years)
• Pregnancy or planned pregnancy, lactating, or unwillingness to use effective contraception.
• Evidence of severe liver disease

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intensified Mycophenolate Sodium (Myfortic) dosing regimen; In patients randomized to the intensified Myfortic dosing regimen, the initial dose was 2-fold of the labeled dose (i.e. 2880 mg/day). The dosage was reduced to standard level in two steps,i.e. reduction to 2160 mg/day after 2 weeks of treatment and to 1440 mg/day after 6 weeks of treatment.	Drug: Enteric-coated mycophenolate sodium (Myfortic); 1440 mg/day for the standard dose. 2880 mg/day for the initial intensified dosage, reduced to standard level in two steps,i.e. reduction to 2160 mg/day after 2 weeks of treatment and to 1440 mg/day after 6 weeks of treatment.; Drug: Cyclosporine (Neoral); cyclosporine microemulsion in galenic form capsules starting at twice a day for a dose of 8-10 mg/kg/day adjusted if necessary to achieve protocol specific target levels; Drug: Prednisone; 20 mg orally per day reduced according to center practice for a minimum dose of 5 mg/day.
Active Comparator: Standard Mycophenolate Sodium (Myfortic) dosing regimen; In patients randomized to the standard Myfortic dosing regimen, the initial dose of 1440 mg/day had to be maintained throughout the whole study.	Drug: Enteric-coated mycophenolate sodium (Myfortic); 1440 mg/day for the standard dose. 2880 mg/day for the initial intensified dosage, reduced to standard level in two steps,i.e. reduction to 2160 mg/day after 2 weeks of treatment and to 1440 mg/day after 6 weeks of treatment.; Drug: Cyclosporine (Neoral); cyclosporine microemulsion in galenic form capsules starting at twice a day for a dose of 8-10 mg/kg/day adjusted if necessary to achieve protocol specific target levels; Drug: Prednisone; 20 mg orally per day reduced according to center practice for a minimum dose of 5 mg/day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Treatment Failure 6-months Post Transplant Measured by the Combined Incidence of Biopsy Proven Acute Rejection, Graft Loss, and Death	To evaluate therapeutic benefit by comparing the efficacy defined as the number of participants with treatment failure (biopsy-proven acute rejection [BPAR], graft loss [GFL] or death) at 6 months post-transplant. BPAR was defined as a biopsy graded IA, IB, IIA, IIB or III using Banff 2000 classification. A graft core biopsy was performed within 24 hours of initiation of anti-rejection therapy. GFL was defined as the day the allograft was presumed lost (the day the patient started dialysis, the day of nephrectomy or the day of irreversible graft loss demonstrated by imaging techniques.)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of Overall Treatment Failure at Days 21 and 84 Post-transplantation Assessed by Biopsy Proven Acute Rejection (BPAR), GFL, and Death	The overall treatment differences of the number of participants with at least one occurrence of the composite event BPAR, GFL or death at study days 21 and 84 post-transplantation. BPAR was defined as a biopsy graded IA, IB, IIA, IIB or III using Banff 2000 classification. A graft core biopsy was performed within 24 hours of initiation of anti-rejection therapy. GFL was defined as the day the allograft was presumed lost (the day the patient started dialysis, the day of nephrectomy or the day of irreversible graft loss demonstrated by imaging techniques.)	21 and 84 days
Renal Function Assessed by Glomerular Filtration Rate (GFR)at Each Visit	The Modification of Diet in Renal Disease (MDRD) formula was used to calculate the GFR. Serum creatinine levels, age, sex and race were used to estimate the GFR levels in mL/min/1.73m^2.	at 21 days, 84 days and 180 days
Renal Function Assessed by Serum Creatinine at Each Visits		at 21 days, 84 days and 180 days

Collaborators and Investigators

• Sponsor: Novartis

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: January 8, 2007
• First Submitted That Met QC Criteria: January 8, 2007
• First Posted (Estimate): January 9, 2007

Study Record Updates

• Last Update Posted (Estimate): March 1, 2011
• Last Update Submitted That Met QC Criteria: February 25, 2011
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: Renal, Kidney, Intensified, Enteric-coated mycophenolate sodium, Transplant
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dermatologic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Antitubercular Agents; Antibiotics, Antitubercular; Calcineurin Inhibitors; Prednisone; Mycophenolic Acid; Cyclosporine; Cyclosporins
• Other Study ID Numbers: CERL080A2419