Pharmacokinetic Profile of Myfortic in Combination With Tacrolimus in Fed Versus Fasting State

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University of Utah
ClinicalTrials.gov Identifier:
NCT00585468
First received: December 21, 2007
Last updated: April 1, 2016
Last verified: April 2016
  Purpose
Literature regarding the effect of food on the pharmacokinetic (PK) profile of enteric-coated mycophenolate sodium combined with tacrolimus and corticosteroid withdrawal is lacking. The objective of this study is to identify pharmacokinetic variables of mycophenolate sodium (Myfortic®) in the fed and fasting state in stable renal transplant patients on tacrolimus in combination with a rapid steroid withdrawal protocol.

Condition Intervention Phase
Kidney Transplantation
Drug: Myfortic
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • Maximum Observed Plasma Concentration (Cmax) of Mycophenolic Acid (MPA) [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose ] [ Designated as safety issue: No ]
  • Minimum Observed Plasma Concentration (Cmin) of Mycophenolic Acid (MPA) [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of Mycophenolic Acid (MPA) [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose ] [ Designated as safety issue: No ]
  • Area Under the Curve (AUC) From Time Zero to 12 Hours Post-Dose [AUC (0-12)] of Mycophenolic Acid (MPA) [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose ] [ Designated as safety issue: No ]
    AUC (0-12) = Area under the plasma concentration versus time curve from time zero (pre-dose) to 12 hours post-dose, measured in microgram-hours per milliliter (mcg*h/mL)

  • Maximum Observed Plasma Concentration (Cmax) of Mycophenolic Acid Glucuronide (MPAG) [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose ] [ Designated as safety issue: No ]
  • Minimum Observed Plasma Concentration (Cmin) of Mycophenolic Acid Glucuronide (MPAG) [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose ] [ Designated as safety issue: No ]
  • Time to Reach Maximum Observed Plasma Concentration (Tmax) of Mycophenolic Acid Glucuronide (MPAG) [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to 12 Hours Post-Dose [AUC (0-12)] of Mycophenolic Acid Glucuronide (MPAG) [ Time Frame: 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose ] [ Designated as safety issue: No ]
    AUC (0-12) = Area under the plasma concentration versus time curve from time zero (pre-dose) to 12 hours post-dose, measured in microgram-hours per milliliter (mcg*h/mL)


Enrollment: 21
Study Start Date: December 2007
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Myfortic - Fed State
Mycophenolate sodium taken with a meal.
Drug: Myfortic
Myfortic 720 mg orally twice daily
Other Names:
  • mycophenolate sodium
  • mycophenolic acid
Experimental: Myfortic - Fasting State
Mycophenolate sodium taken separately from food by 2 hours.
Drug: Myfortic
Myfortic 720 mg orally twice daily
Other Names:
  • mycophenolate sodium
  • mycophenolic acid

Detailed Description:

Mycophenolate sodium (Myfortic®) is an antiproliferative immunosuppressant used in renal transplantation. Mycophenolate sodium is formulated as an enteric coated tablet that releases mycophenolic acid (MPA) which in turn inhibits inosine monophosphate dehydrogenase (IMPDH). Through inhibition of IMPDH, the de novo pathway of purine synthesis, which T and B lymphocytes rely on for proliferation, is blocked. The pharmacokinetic profile of mycophenolate sodium has mainly been studied in combination with cyclosporine and steroids. There is little information on the pharmacokinetics of mycophenolate sodium in combination with tacrolimus and currently no published information in steroid withdrawal. 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 two-drug maintenance immunosuppression regimen. The study will assess the pharmacokinetic profile of mycophenolate sodium in patients on tacrolimus dose adjusted based on levels, and a steroid withdrawal protocol.

Renal transplant patients will act as their own controls in a randomized crossover design with pharmacokinetic profiles occurring at two different time points. Immunosuppression will consist of induction therapy with maintenance immunosuppression consisting of tacrolimus plus mycophenolate sodium. Corticosteroids will be withdrawn per institutional protocol within the first week post transplant.

Approximately 3-4 weeks post transplant, patients that met enrollment criteria and have consented to participate in the study will be instructed to take 720 milligrams of mycophenolate sodium orally twice daily for one week either separated from food by two hours (fasting state) or with a meal (fed state). After one week, patients will be admitted for approximately 24 hours where they will continue to receive mycophenolate sodium with or without food. During this period, blood samples will be drawn at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 hours following the dose to evaluate levels of mycophenolic acid (MPA) and mycophenolic acid glucuronide (MPAG). After 24 hours, patients will be discharged with instructions to take mycophenolate sodium in the opposite manner (fed or fasting state) than they had the week before. At the end of the second week the patients will return for a second PK evaluation with blood collection at the same time points following mycophenolate sodium dosing.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • Taking medications that may alter the metabolism of tacrolimus or mycophenolate sodium
  • Experienced an acute rejection episode prior to the pharmacokinetic profile collection
  • Serum creatinine >2 mg/dL
  • Neutropenia (Absolute Neutrophil Count < 1.3x10^3/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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00585468

Locations
United States, Utah
Univ of Utah-Solid Organ Transplant
Salt Lake City, Utah, United States, 84119
Sponsors and Collaborators
University of Utah
Investigators
Principal Investigator: Fuad Shihab, MD University of Utah
  More Information

Publications:
Responsible Party: University of Utah
ClinicalTrials.gov Identifier: NCT00585468     History of Changes
Other Study ID Numbers: 15121  Award# CERL080AUS33 
Study First Received: December 21, 2007
Results First Received: September 10, 2013
Last Updated: April 1, 2016
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Tacrolimus
Mycophenolate mofetil
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 25, 2016