Comparative Bioavailability of Myfenax® and CellCept® in Kidney Transplant Patients

Phase 4

Terminated

Conditions: Stable Renal Transplant Recipients

Interventions: Drug: mycophenolate mofetil (Myfenax)
Drug: mycophenolate mofetil (Cellcept)

Registration Number: NCT00991510

Lead Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 43

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Reference/Test/Test	mycophenolate mofetil (Cellcept)	The reference product was CellCept® and test product was Myfenax®. In period I, participants received CellCept on Days 1-14. In period II, participants crossed-over to receive Myfenax on Days 15-28. In period III, participants received Myfenax until the end of the study (Days 29-112). Doses of mycophenolate mofetil were at least 500 mg twice daily, morning and evening.
Test/Reference/Reference	mycophenolate mofetil (Cellcept)	The test product was Myfenax® and the reference product was CellCept®. In period I, participants received Myfenax on Days 1-14. In period II, participants crossed-over to receive CellCept on Days 15-28. In period III, participants received CellCept until the end of the study (Days 29-112). Doses of mycophenolate mofetil were at least 500 mg twice daily, morning and evening.
Reference/Test/Test	mycophenolate mofetil (Myfenax)	The reference product was CellCept® and test product was Myfenax®. In period I, participants received CellCept on Days 1-14. In period II, participants crossed-over to receive Myfenax on Days 15-28. In period III, participants received Myfenax until the end of the study (Days 29-112). Doses of mycophenolate mofetil were at least 500 mg twice daily, morning and evening.
Test/Reference/Reference	mycophenolate mofetil (Myfenax)	The test product was Myfenax® and the reference product was CellCept®. In period I, participants received Myfenax on Days 1-14. In period II, participants crossed-over to receive CellCept on Days 15-28. In period III, participants received CellCept until the end of the study (Days 29-112). Doses of mycophenolate mofetil were at least 500 mg twice daily, morning and evening.

Primary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax) of Mycophenolate Mofetil	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	Cmax was directly obtained from measured values of plasma concentrations.
Area Under the Plasma Concentration-time Curve (AUC(0-tau)) of Mycophenolate Mofetil	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	For participants with a 0-12h profile: Area under the plasma concentration-time curve during a dosage interval at steady state (calculated using the trapezoidal rule, from t = 0 to t = 12 hours). For participants with a 0-6h profile: AUC(0-tau) was calculated based on AUC(0-6h) using the extrapolation formula according to Fleming.
Area Under the Plasma Concentration-time Curve (AUC(0-6h)) of Mycophenolate Mofetil	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	Area under the plasma concentration-time curve during a dosage interval at steady state (calculated using the trapezoidal rule, from t = 0 to t = 6 hours).

Secondary Outcome Measures

Name	Time	Method
Time Corresponding to Occurrence of Cmax (Tmax) of Mycophenolate Mofetil	Day 14 and Day 28 (end of first two cross-over periods) before drug administration	Tmax was directly obtained from measured values.
Summary of Participants With Adverse Events	Day 1 up to Day 112	Summary of adverse events across three study time periods. The on-treatment time frame spanned the time during which study drug was administered. Relation to study drug was assessed by the investigator. The Adverse Event count includes serious and non-serious AEs. A serious AE (SAE) was any event that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or congenital anomaly/birth defect or was an important medical event could have jeopardized the patient's safety or required medical or surgical intervention to prevent one of the outcomes listed above. Severity was measured on a three-point scale: mild, moderate, severe.
Degree of Fluctuation of the Concentration Levels of Mycophenolate Mofetil Over One Dosing Interval (PTF)	Day 14 and Day 28 (end of first two cross-over periods) before drug administration	PTF was calculated as: (Cmax-Cmin)/(AUCt/t)\*100
Minimum Observed Plasma Concentration (Cmin) of Mycophenolate Mofetil	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	Cmin was directly obtained from measured values of plasma concentrations.
Plasma Concentrations of Mycophenolate Mofetil in Pre-Administration Samples (Cpd)	Day 14 and Day 28 (end of first two cross-over periods) before drug administration	Cpd was directly obtained from measured values of plasma concentrations.