Clinical trial NCT00991510: Comparative Bioavailability of Myfenax® and CellCept® in Kidney Transplant Patients
Official title: Comparative Bioavailability of Myfenax® (Teva) and CellCept® (Roche) in Stable Patients After Renal Transplantation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Stable Renal Transplant Recipients
Keywords: renal transplantation
mycophenolate mofetil
pharmacokinetics
immunosuppression
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2009-10-08
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to further investigate how much of the drug substance "mycophenolate mofetil" can be found in the blood of patients with kidney or renal transplants when treated with Myfenax® or CellCept®. Additionally, the safety and side effects of the two products will be compared. All information already available on these products indicates that the safety profiles of the two products will be the same.


Eligibility criteria: Inclusion Criteria:

* Renal transplant recipients at least 12 months post-transplantation aged ≥ 18 years.
* Maintenance treatment with mycophenolate mofetil (in combination with tacrolimus with or without corticosteroids).
* Stable dose of mycophenolate mofetil (≥ 500 mg twice daily) with no changes in immunosuppressive regimen for at least 6 weeks prior to the start of the study.
* Stable renal graft function for at least 3 months.
* Female patients must be either post-menopausal for ≥ 1 year, be surgically sterilized or a negative pregnancy test will be required immediately prior to study entry and such patients must continue to use effective contraception.
* Willingness to undergo the study-related procedures.
* Ability to comprehend and willingness to sign informed consent form.

Exclusion Criteria:

* History of allergy to mycophenolate mofetil, mycophenolic acid or any of the ingredients.
* Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any organ other than kidney.
* Rejection within the past 6 months prior to the start of the study.
* Severe clinically relevant co-existing disease.
* History of cancer other than skin cancer that has been cured.
* History of serious clinically relevant digestive system disease during the last 12 months prior to start of the study.
* Known or suspected hereditary deficiency of hypoxanthine-guanine-phosphoribosyltransferase (e.g., Lesch-Nyhan syndrome, Kelley-Seegmiller syndrome).
* Known or suspected liver impairment.
* Clinically significant thrombocytopenia, anaemia, leukopenia, or neutropenia
* Clinically significant laboratory and/or physical changes during the last 2 months prior to the start of the study.
* Use of azathioprine, cholestyramine, sevelamer, or probenecid within 2 weeks prior to the first administration of study medication.
* Change in concomitant medication during the 6 weeks prior to start of the study.
* Use of any drug, prescribed or over-the-counter, (except stable concomitant medication) within 2 weeks prior to the first administration of study medication.
* Planned or expected requirement for the use of live attenuated vaccines during the study.
* Positive testing for HIV, Hepatitis B and C.
* Clinical symptoms or laboratory evidence of cytomegalovirus infection in the last 6 month.
* Pregnant or breast-feeding women.
* Women of childbearing potential unable or unwilling to practice effective contraceptive measures for the duration of the study and for 6 weeks after the end of the study.
* History of known or suspected alcohol or drug abuse.
* Any other condition of the patient that, in the opinion of the investigator may compromise evaluation of the study treatment or may jeopardize patient's compliance or adherence to protocol requirements.
* Previous enrollment in this study or participation in any other drug investigational trial within the past 6 weeks prior to enrollment.

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve (AUC(0-6h)) of Mycophenolate Mofetil
timeFrame: Day 14 and Day 28 (end of first two cross-over periods) before drug administration and at 30 min, 1 hour, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after drug administration
measure: Area Under the Plasma Concentration-time Curve (AUC(0-tau)) of Mycophenolate Mofetil
timeFrame: Day 14 and Day 28 (end of first two cross-over periods) before drug administration and at 30 min, 1 hour, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after drug administration
measure: Maximum Observed Plasma Concentration (Cmax) of Mycophenolate Mofetil
timeFrame: Day 14 and Day 28 (end of first two cross-over periods) before drug administration and at 30 min, 1 hour, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after drug administration
Secondary outcomes:
measure: Minimum Observed Plasma Concentration (Cmin) of Mycophenolate Mofetil
timeFrame: Day 14 and Day 28 (end of first two cross-over periods) before drug administration and at 30 min, 1 hour, 1.5, 2, 3, 4, 5, 6, 8, 10, and 12 hours after drug administration
measure: Plasma Concentrations of Mycophenolate Mofetil in Pre-Administration Samples (Cpd)
timeFrame: Day 14 and Day 28 (end of first two cross-over periods) before drug administration
measure: Degree of Fluctuation of the Concentration Levels of Mycophenolate Mofetil Over One Dosing Interval (PTF)
timeFrame: Day 14 and Day 28 (end of first two cross-over periods) before drug administration
measure: Time Corresponding to Occurrence of Cmax (Tmax) of Mycophenolate Mofetil
timeFrame: Day 14 and Day 28 (end of first two cross-over periods) before drug administration
measure: Summary of Participants With Adverse Events
timeFrame: Day 1 up to Day 112
Other outcomes:
Locations:
Study officials:
affiliation: Medical University Vienna
name: Gere Sunder-Plassman, Prof.,MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sunder-Plassmann G et al.: Results of a Comparative Bioavailability Study of Myfenax (Teva) and CellCept (Roche) in Stable Kidney Transplant Recipients. American Transplant Congress 2011. Abstract Number: 250308
citation: Sunder-Plassmann G, Reinke P, Rath T, Wiecek A, Nowicki M, Moore R, Lutz J, Gaggl M, Ferkl M. Comparative pharmacokinetic study of two mycophenolate mofetil formulations in stable kidney transplant recipients. Transpl Int. 2012 Jun;25(6):680-6. doi: 10.1111/j.1432-2277.2012.01475.x. Epub 2012 Apr 16.