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

April 1, 2016 updated by: University of Utah

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Corticosteroids will be withdrawn per institutional protocol within the first week post transplant.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.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Utah
      • Salt Lake City, Utah, United States, 84119
        • Univ of Utah-Solid Organ Transplant

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Myfortic - Fed State
Mycophenolate sodium taken with a meal.
Drug: Myfortic
Myfortic 720 mg orally twice daily
Other Names:
  • mycophenolic acid
  • mycophenolate sodium
Experimental: Myfortic - Fasting State
Mycophenolate sodium taken separately from food by 2 hours.
Drug: Myfortic
Myfortic 720 mg orally twice daily
Other Names:
  • mycophenolic acid
  • mycophenolate sodium

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
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
0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
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
0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
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
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)
0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
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
0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
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
0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
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
0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose
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
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)
0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 hours post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Utah

Investigators

  • Principal Investigator: Fuad Shihab, MD, University of Utah

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2007

Primary Completion (Actual)

July 1, 2011

Study Completion (Actual)

July 1, 2011

Study Registration Dates

First Submitted

December 21, 2007

First Submitted That Met QC Criteria

December 21, 2007

First Posted (Estimate)

January 3, 2008

Study Record Updates

Last Update Posted (Estimate)

May 6, 2016

Last Update Submitted That Met QC Criteria

April 1, 2016

Last Verified

April 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15121
  • Award# CERL080AUS33 (Other Grant/Funding Number: Novartis Pharmaceuticals)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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