Clinical trial NCT01467011: Myfortic, Prograf, and Corticosteroids in de Novo Liver Transplantation
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: End Stage Liver Disease
Keywords: Myfortic
Mycophenolic acid
Prograf
Tacrolimus
Liver transplantation
Lead sponsor: The Methodist Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2011-11-08
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with end stage liver disease who are receiving a liver transplant at The Methodist Hospital in Houston, Texas and who satify the inclusion/exclusion criteria will be considered for the study.

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetic parameters
timeFrame: Twelve hour pharmacokinetics at one week, one month, and six months post transplant
Secondary outcomes:
measure: Safety and tolerability
timeFrame: 1 week, 1 month, 6 months
Other outcomes:
Locations:
city: Houston
country: United States
facility: The Methodist Hospital System
state: Texas
Study officials:
affiliation: The Methodist Hospital Research Institute
name: R M Ghobrial, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1097/00000658-200108000-00015.
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.
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. doi: 10.1177/0091270004270145.
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. doi: 10.1177/00912700122010087.
citation: 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. doi: 10.1111/j.1399-0012.2004.00318.x.
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. doi: 10.1111/j.1399-0012.2007.00662.x.
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.