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Completed

NCT Number: NCT00585468

Pharmacokinetic Profile of Myfortic in Combination With Tacrolimus in Fed Versus 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.

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Key information

Conditions

Kidney Transplantation

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Univ of Utah-Solid Organ Transplant

Salt Lake City, Utah, 84119, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Myfortic

Drug

Myfortic 720 mg orally twice daily

Other names: mycophenolate sodium, mycophenolic acid

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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)

  5. 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

  6. 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

  7. 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

  8. 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)

Sponsors and collaborators

Lead sponsor

University of Utah

Other

Registry information

Official study 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

Important dates

Study start
2007
Primary completion
2011
Study completion
2011
First posted
Jan 3, 2008
Registry last updated
May 6, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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