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Trial record 16 of 1167 for:    MYCOPHENOLIC ACID

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

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ClinicalTrials.gov Identifier: NCT00585468
Recruitment Status : Completed
First Posted : January 3, 2008
Results First Posted : May 6, 2016
Last Update Posted : May 6, 2016
Sponsor:
Information provided by (Responsible Party):
University of Utah

Tracking Information
First Submitted Date  ICMJE December 21, 2007
First Posted Date  ICMJE January 3, 2008
Results First Submitted Date  ICMJE September 10, 2013
Results First Posted Date  ICMJE May 6, 2016
Last Update Posted Date May 6, 2016
Study Start Date  ICMJE December 2007
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 1, 2016)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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)
Original Primary Outcome Measures  ICMJE
 (submitted: December 21, 2007)
Outcomes measured will include Cmax, Cmin, Tmax and AUC for Myfortic metabolites (MPA, MPAG, AcMPAG, freeMPA) and tacrolimus [ Time Frame: Dec 2007-Dec 2008 ]
Change History Complete list of historical versions of study NCT00585468 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: December 21, 2007)
Outcomes measured will include Cmax, Cmin, Tmax and AUC for Myfortic metabolites (MPA, MPAG, AcMPAG, freeMPA) and tacrolimus [ Time Frame: Dec 2007-Dec 2008 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetic Profile of Myfortic in Combination With Tacrolimus in Fed Versus Fasting State
Official Title  ICMJE 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
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Kidney Transplantation
Intervention  ICMJE Drug: Myfortic
Myfortic 720 mg orally twice daily
Other Names:
  • mycophenolate sodium
  • mycophenolic acid
Study Arms  ICMJE
  • Experimental: Myfortic - Fed State
    Mycophenolate sodium taken with a meal.
    Intervention: Drug: Myfortic
  • Experimental: Myfortic - Fasting State
    Mycophenolate sodium taken separately from food by 2 hours.
    Intervention: Drug: Myfortic
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 1, 2016)
21
Original Estimated Enrollment  ICMJE
 (submitted: December 21, 2007)
14
Actual Study Completion Date  ICMJE July 2011
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00585468
Other Study ID Numbers  ICMJE 15121
Award# CERL080AUS33 ( Other Grant/Funding Number: Novartis Pharmaceuticals )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Utah
Study Sponsor  ICMJE University of Utah
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Fuad Shihab, MD University of Utah
PRS Account University of Utah
Verification Date April 2016

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