Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00369278
First received: August 25, 2006
Last updated: March 25, 2011
Last verified: March 2011

August 25, 2006
March 25, 2011
June 2006
December 2008   (final data collection date for primary outcome measure)
  • Time to First Occurrence of a Mycophenolic Acid (MPA) Plasma Concentration of ≥ 40 mg*h/L [ Time Frame: Assessed on day 3, 10, 21, 42, 56 and 84 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Median time to first occurrence of treatment failure was not reached in this study.
  • Number of Participants With Any Treatment Failure [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.
  • Time to occurrence of treatment failure during the first 6 months post-treatment or at month 6 post-treatment
  • Stage I:
  • MPA exposure at different time points after transplantation
  • Time to achieve an MPA exposure of ≥ 40 mg*h/mL on day 3, day 10, day 21, day 42, day 56, and day 84
  • Stage II:
Complete list of historical versions of study NCT00369278 on ClinicalTrials.gov Archive Site
  • Number of Participants With Single Treatment Failures [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Due to a small number of events, median time to <event> was not reached.
  • Renal Function as Measured by Serum Creatinine [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Renal Function as Measured by Glomerular Filtration Rate (GFR) [ Time Frame: 6 months ] [ Designated as safety issue: No ]

    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.
  • Stage I:
  • Safety and tolerability of EC-MPS during the study
  • Incidence of acute rejection and graft loss during the study
  • Pharmacokinetic profile of EC-MPS by determination of MPA metabolites and the free fraction of MPA on day 3, day 10, day 21, day 42, day 56, and day 84
  • IMPDH (inosine monophosphate dehydrogenase) activity and pharmacokinetic-pharmaco-dynamic relationship at baseline, day 3, day 10, day 21, and day 56
  • Stage II:
  • Occurrence of treatment failures at day 28 and day 84
  • Rates of events for treated acute rejection, death, graft loss, or loss to follow up on day 28, day 84, and day 180
  • All individual components of the composite endpoint “treatment failure”, including the assessment of the rate of clinical rejections
  • Time to “event” for the composite endpoint as well as all individual components of that endpoint “treatment failure” including clinical rejections
  • Renal function as measured by serum creatinine and glomerular filtration rate on day 3, day 10, day 14, day 21, day 42, day 56, day 84, and at the end of study
Not Provided
Not Provided
 
Intensified vs. Standard Dose Therapy With Mycophenolate Sodium Plus Cyclosporin Microemulsion and Corticosteroid Combination in Patients With de Novo Renal Transplant Patients
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

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).

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Renal Transplantation
Drug: Enteric-coated mycophenolate sodium (EC-MPS)
Tablets for oral administration
Other Name: myfortic
  • Experimental: Intensified Mycophenolate sodium
    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.
    Intervention: Drug: Enteric-coated mycophenolate sodium (EC-MPS)
  • Active Comparator: Standard Mycophenolate sodium
    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.
    Intervention: Drug: Enteric-coated mycophenolate sodium (EC-MPS)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
128
December 2008
December 2008   (final data collection date for primary outcome measure)

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

Both
18 Years to 70 Years
Not Provided
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT00369278
CERL080ADE12
Not Provided
External Affairs, Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Novartis
Novartis
March 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP