Myfortic, Prograf, and Corticosteroids in de Novo Liver Transplantation

End Stage Liver Disease Clinical Trial

Official title:

An Open-label Study of the Pharmacokinetics of Mycophenolic Acid as Myfortic (Enteric-coated Mycophenolate Sodium) When Used in Combination With Prograf (Tacrolimus) and Corticosteroids in Patients Undergoing de Novo Liver Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01467011
• Other study ID #: Pro00004722
• Status: Completed
• Start date: December 2010
• Est. completion date: December 2013

Study information

• Verified date: May 2018
• Source: The Methodist Hospital System
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to gather information regarding the use of Myfortic, Prograf, and corticosteroids in new liver transplant recipients. These three medicines help to prevent the body from rejecting the transplanted liver. The information the investigators are obtaining is data relating to the process of Myfortic absorption by the body, its distribution in the body, the breakdown of Myfortic in the body, and its elimination from the body. This absorption, distribution, breakdown, and elimination is called pharmacokinetics.

Description:

Myfortic is approved for use in kidney transplant recipients, and has been prescribed by doctors for liver transplant recipients. No study has been reported to date evaluating the pharmacokinetics of Myfortic in new liver transplant recipients who also take Prograf and corticosteroids. During this six month study, a series of blood samples will be obtained after subjects take Myfortic, Prograf, and corticosteroids.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adults > or equal to age 18 years

• Planned to receive tacrolimus and corticosteroid therapy posttransplant

• Serum creatinine at transplant < or equal to 2.5mg/dL

• UCSF tumor staging < 8cm total

• Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to the baseline visit and are required to practice a reliable method of contraception for the duration of the study and for no fewer than 6 weeks after completing the study.

• Signed informed consent form prior to any research assessment

Exclusion Criteria:

• Induction therapy

• Requiring dialysis at the time of transplant

• Organ transplant other than liver

• Pregnant or nursing females

• Women of childbearing potential not practicing reliable methods of contraception. Reliable methods for contraception include surgical sterilization (hysterectomy, bilateral tubal ligation), double-barrier method (such as condom and diaphragm). To be considered as post-menopausal and not of childbearing potential, female subjects must have experienced 12 consecutive months of amenorrhea.

• Require any medications that interfere with metabolism of Myfortic (other than corticosteroids)

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

• Participation in a study of investigational drug in the previous 30 days or 5 half-lives of the investigational drug

Related Conditions & MeSH terms

• End Stage Liver Disease
• Liver Diseases

Intervention

Drug:
• Enteric-coated Mycophenolate Sodium
1440mg/day for 6 months posttransplant

Locations

Country	Name	City	State
United States	The Methodist Hospital System	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
R. Mark Ghobrial, MD	Novartis

Country where clinical trial is conducted

United States, 

References & Publications (7)

Arns W, Breuer S, Choudhury S, Taccard G, Lee J, Binder V, Roettele J, Schmouder R. Enteric-coated mycophenolate sodium delivers bioequivalent MPA exposure compared with mycophenolate mofetil. Clin Transplant. 2005 Apr;19(2):199-206. — View Citation

de Carvalho L, Parise ER, Samuel D. Factors associated with nutritional status in liver transplant patients who survived the first year after transplantation. J Gastroenterol Hepatol. 2010 Feb;25(2):391-6. doi: 10.1111/j.1440-1746.2009.06033.x. Epub 2009 Nov 19. — View Citation

Jain A, Venkataramanan R, Hamad IS, Zuckerman S, Zhang S, Lever J, Warty VS, Fung JJ. Pharmacokinetics of mycophenolic acid after mycophenolate mofetil administration in liver transplant patients treated with tacrolimus. J Clin Pharmacol. 2001 Mar;41(3):268-76. — View Citation

Kaczmarek I, Bigdeli AK, Vogeser M, Mueller T, Beiras-Fernandez A, Kaczmarek P, Schmoeckel M, Meiser B, Reichart B, Ueberfuhr P. Defining algorithms for efficient therapeutic drug monitoring of mycophenolate mofetil in heart transplant recipients. Ther Drug Monit. 2008 Aug;30(4):419-27. doi: 10.1097/FTD.0b013e31817d7064. — View Citation

Perry TW, Christians U, Trotter JF, Bendrick-Peart J. Pharmacokinetics of enteric-coated mycophenolate sodium in stable liver transplant recipients. Clin Transplant. 2007 May-Jun;21(3):413-6. — View Citation

Pisupati J, Jain A, Burckart G, Hamad I, Zuckerman S, Fung J, Venkataramanan R. Intraindividual and interindividual variations in the pharmacokinetics of mycophenolic acid in liver transplant patients. J Clin Pharmacol. 2005 Jan;45(1):34-41. — View Citation

Plank LD, Metzger DJ, McCall JL, Barclay KL, Gane EJ, Streat SJ, Munn SR, Hill GL. Sequential changes in the metabolic response to orthotopic liver transplantation during the first year after surgery. Ann Surg. 2001 Aug;234(2):245-55. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetic parameters	Pharmacokinetic time points will be obtained at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 8, and 12 hours post dose. The exposure (area under the concentration-time curve, AUC µg·h/mL, Cmax ng/mL, and Tmax, hours) of MPA and MPAG will be calculated using non-compartmental analysis.	Twelve hour pharmacokinetics at one week, one month, and six months post transplant
Secondary	Safety and tolerability	MPA exposure will be assessed at one week, 1 month, and 6 months. Kidney function (using MDRD and Cockcroft-Gault) will be compared with PK parameters and graft survival recorded. Adverse events will be recorded.	1 week, 1 month, 6 months