Pharmacokinetic Profile of Myfortic (Enteric Coated Mycophenolate Sodium) in a Rapid Steroid Withdrawal Protocol

Kidney Transplant Clinical Trial

Official title:

Pharmacokinetic Profile of Myfortic (Enteric Coated Mycophenolate Sodium) in a Rapid Steroid Withdrawal Protocol in Combination With Tacrolimus in Stable Renal Transplant Recipients in the Fed and Fasting State

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00585468
• Other study ID #: 15121
• Secondary ID: Award# CERL080AU
• Status: Completed
• Phase: Phase 4
• First received: December 21, 2007
• Last updated: October 18, 2012
• Start date: December 2007
• Est. completion date: July 2011

Study information

• Verified date: October 2012
• Source: University of Utah
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Mycophenolate sodium (Myfortic®) is an antiproliferative immunosuppressant used in transplantation. It was developed with the intention of improving the gastrointestinal side effect profile of mycophenolate mofetil (CellCept®). Mycophenolate sodium is formulated as an enteric coated tablet that releases mycophenolic acid (MPA) which in turn inhibits inosine monophosphate dehydrogenase (IMPDH).1 Through inhibition of IMPDH the de novo pathway of purine synthesis, which T and B lymphocytes rely on for proliferation, is blocked.1 The pharmacokinetic profile of mycophenolate sodium has mainly been studied in combination with cyclosporine and steroids.2 There is little information on the pharmacokinetics of mycophenolate sodium in combination with tacrolimus3 and currently no published information in steroid withdrawal. The metabolism and pharmacokinetics of mycophenolic acid differ when combined with cyclosporine or tacrolimus, leading to increased area under the curve (AUC) and Cmin with tacrolimus.4 The decrease in AUC with cyclosporine is due to an inhibition of MPAG excretion5, thus preventing the enterohepatic recirculation of MPAG and conversion back to MPA that is seen with tacrolimus. Mycophenolate sodium pharmacokinetics in the fed state have demonstrated a decrease of 33% in Cmax compared to a fasting state, as well as a delay in Tmax and lag time.1 However AUC, representing systemic exposure to MPA, was not significantly effected by food.1 The AUC values may vary by 20% or greater when mycophenolate sodium is administered with food. All current published data on the pharmacokinetics of MPA have been in patients receiving chronic corticosteroids as part of their immunosuppression regimen. As immunosuppression minimization, and especially corticosteroid withdrawal, become more popular it is important to understand how mycophenolate sodium and its metabolites behave in a 2 drug maintenance immunosuppression regimen. We propose to study the pharmacokinetic profile of mycophenolate sodium in patients on tacrolimus dose adjusted based on levels, and a steroid withdrawal protocol.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Renal transplant recipients greater than 18 years of age, who have given written consent

Exclusion Criteria:

• taking medications that will interfere with the metabolism of the metabolism of tacrolimus or mycophenolate sodium

• experienced an acute rejection episode prior to their pharmacokinetic profiles and if they have a serum creatinine >2 mg/dL

• neutropenia (ANC < 1.3x103/mL)

• received a previous transplant other than a kidney

• receiving chronic steroids at time of transplant

• known hypersensitivity to tacrolimus, mycophenolate mofetil, mycophenolate sodium, mycophenolic acid or any of its excipients

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Transplant

Intervention

Drug:
• Myfortic
Drug-immunosuppressant

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Utah

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Outcomes measured will include Cmax, Cmin, Tmax and AUC for Myfortic metabolites (MPA, MPAG, AcMPAG, freeMPA) and tacrolimus		Dec 2007-Dec 2008	No
Secondary	Outcomes measured will include Cmax, Cmin, Tmax and AUC for Myfortic metabolites (MPA, MPAG, AcMPAG, freeMPA) and tacrolimus		Dec 2007-Dec 2008	No