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TerminatedNCT00991510Updated Nov 8, 2018Results posted

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

A Phase 4 interventional study of mycophenolate mofetil (Myfenax) and mycophenolate mofetil (Cellcept) in Stable Renal Transplant Recipients, sponsored by Teva Branded Pharmaceutical Products R&D, Inc.. Terminated. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-11-08.

Sponsored by Teva Branded Pharmaceutical Products R&D, Inc. · Phase 4, Interventional, and Treatment

Why this study was terminated
Slow recruitment and lack of time to product launch
Phase
Phase 4
Study type
Interventional
Enrollment
43
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Stable Renal Transplant Recipients

Keywords

  • renal transplantation
  • mycophenolate mofetil
  • pharmacokinetics
  • immunosuppression
03

In context

Lead sponsor

Teva Branded Pharmaceutical Products R&D, Inc. is the lead sponsor of 205 studies on the registry; none are open to participants now.

Of its 49 completed or terminated interventional studies of FDA-regulated products, 47 (96%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
43 participants (actual)

Study arms

  • Experimental
    Reference/Test/Test

    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.

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

  • Experimental
    Test/Reference/Reference

    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.

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

Interventions

  • Drugmycophenolate mofetil (Myfenax)

    Each participant received at least 500 mg orally, twice daily (morning and evening) during those study periods labeled as 'T' (test drug). Participants receive the dose equivalent to the pre-study dose (within the recommended therapeutic range) of mycophenolate mofetil.

    Also known as: Myfenax®

  • Drugmycophenolate mofetil (Cellcept)

    Each participant received at least 500 mg orally, twice daily (morning and evening) during those study periods labeled as 'R' (reference drug). Participants receive the dose equivalent to the pre-study dose (within the recommended therapeutic range) of mycophenolate mofetil.

    Also known as: CellCept®

06

What researchers measure

Primary outcomes

  1. Area Under the Plasma Concentration-time Curve (AUC(0-6h)) of Mycophenolate Mofetil

    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).

    Time frame: 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

  2. Area Under the Plasma Concentration-time Curve (AUC(0-tau)) of Mycophenolate Mofetil

    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.

    Time frame: 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

  3. Maximum Observed Plasma Concentration (Cmax) of Mycophenolate Mofetil

    Cmax was directly obtained from measured values of plasma concentrations.

    Time frame: 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

  1. Minimum Observed Plasma Concentration (Cmin) of Mycophenolate Mofetil

    Cmin was directly obtained from measured values of plasma concentrations.

    Time frame: 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

  2. Plasma Concentrations of Mycophenolate Mofetil in Pre-Administration Samples (Cpd)

    Cpd was directly obtained from measured values of plasma concentrations.

    Time frame: Day 14 and Day 28 (end of first two cross-over periods) before drug administration

  3. Degree of Fluctuation of the Concentration Levels of Mycophenolate Mofetil Over One Dosing Interval (PTF)

    PTF was calculated as: (Cmax-Cmin)/(AUCt/t)\*100

    Time frame: Day 14 and Day 28 (end of first two cross-over periods) before drug administration

  4. Time Corresponding to Occurrence of Cmax (Tmax) of Mycophenolate Mofetil

    Tmax was directly obtained from measured values.

    Time frame: Day 14 and Day 28 (end of first two cross-over periods) before drug administration

  5. Summary of Participants With Adverse Events

    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.

    Time frame: Day 1 up to Day 112

07

Results

Posted Jul 30, 2013
Limitations and caveats
The study was designed to have a power of at least 80 % to show bioequivalence with 80 subjects. Only 43 subjects were included.

Participant flow

Period I (Days 1-14)
Participant flow — Period I (Days 1-14)
MilestoneReference/Test/TestTest/Reference/Reference
Started2221
Completed2121
Not completed10
Withdrew: Adverse event10
Period II (Days 15-28)
Participant flow — Period II (Days 15-28)
MilestoneReference/Test/TestTest/Reference/Reference
Started2121
Completed2121
Not completed00
Period III (Days 29-112)
Participant flow — Period III (Days 29-112)
MilestoneReference/Test/TestTest/Reference/Reference
Started2121
Completed2020
Not completed11
Withdrew: Adverse event11

Outcome measures

PrimaryArea Under the Plasma Concentration-time Curve (AUC(0-6h)) of Mycophenolate Mofetil

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).

Time frame:
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
Reported as:
Mean · hour* µg /ml
Area Under the Plasma Concentration-time Curve (AUC(0-6h)) of Mycophenolate Mofetil
hour* µg /mlCellCeptMyfenax
Area Under the Plasma Concentration-time Curve (AUC(0-6h)) of Mycophenolate Mofetil33.523 ± 15.126531.100 ± 15.4198
Statistical analysis
  • CellCept vs Myfenax · ANOVA · Adjusted least-squares mean ratio: 0.923 · 90% CI 0.865 to 0.984
PrimaryArea Under the Plasma Concentration-time Curve (AUC(0-tau)) of Mycophenolate Mofetil

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.

Time frame:
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
Reported as:
Mean · hour* µg /ml
Area Under the Plasma Concentration-time Curve (AUC(0-tau)) of Mycophenolate Mofetil
hour* µg /mlCellCeptMyfenax
Area Under the Plasma Concentration-time Curve (AUC(0-tau)) of Mycophenolate Mofetil49.846 ± 20.827848.255 ± 21.2246
Statistical analysis
  • CellCept vs Myfenax · ANOVA · Adjusted least-squares mean ratio: 0.959 · 90% CI 0.899 to 1.023
PrimaryMaximum Observed Plasma Concentration (Cmax) of Mycophenolate Mofetil

Cmax was directly obtained from measured values of plasma concentrations.

Time frame:
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
Reported as:
Mean · µg /ml
Maximum Observed Plasma Concentration (Cmax) of Mycophenolate Mofetil
µg /mlCellCeptMyfenax
Maximum Observed Plasma Concentration (Cmax) of Mycophenolate Mofetil16.189 ± 9.944814.308 ± 8.3432
Statistical analysis
  • CellCept vs Myfenax · ANOVA · Adjusted least-squares mean ratio: 0.873 · 90% CI 0.787 to 0.968
SecondaryMinimum Observed Plasma Concentration (Cmin) of Mycophenolate Mofetil

Cmin was directly obtained from measured values of plasma concentrations.

Time frame:
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
Reported as:
Mean · µg /ml
Minimum Observed Plasma Concentration (Cmin) of Mycophenolate Mofetil
µg /mlCellCeptMyfenax
Minimum Observed Plasma Concentration (Cmin) of Mycophenolate Mofetil1.584 ± 0.78011.567 ± 0.7387
Statistical analysis
  • CellCept vs Myfenax · ANOVA · Adjusted least-squares mean ratio: 0.985 · 90% CI 0.877 to 1.106
SecondaryPlasma Concentrations of Mycophenolate Mofetil in Pre-Administration Samples (Cpd)

Cpd was directly obtained from measured values of plasma concentrations.

Time frame:
Day 14 and Day 28 (end of first two cross-over periods) before drug administration
Reported as:
Mean · µg /ml
Plasma Concentrations of Mycophenolate Mofetil in Pre-Administration Samples (Cpd)
µg /mlCellCeptMyfenax
Plasma Concentrations of Mycophenolate Mofetil in Pre-Administration Samples (Cpd)2.693 ± 1.70013.001 ± 2.0863
SecondaryDegree of Fluctuation of the Concentration Levels of Mycophenolate Mofetil Over One Dosing Interval (PTF)

PTF was calculated as: (Cmax-Cmin)/(AUCt/t)\*100

Time frame:
Day 14 and Day 28 (end of first two cross-over periods) before drug administration
Reported as:
Mean · percentage of AUC for a dosing interval
Degree of Fluctuation of the Concentration Levels of Mycophenolate Mofetil Over One Dosing Interval (PTF)
percentage of AUC for a dosing intervalCellCeptMyfenax
Degree of Fluctuation of the Concentration Levels of Mycophenolate Mofetil Over One Dosing Interval (PTF)351.05 ± 161.195323.67 ± 156.018
SecondaryTime Corresponding to Occurrence of Cmax (Tmax) of Mycophenolate Mofetil

Tmax was directly obtained from measured values.

Time frame:
Day 14 and Day 28 (end of first two cross-over periods) before drug administration
Reported as:
Mean · hours
Time Corresponding to Occurrence of Cmax (Tmax) of Mycophenolate Mofetil
hoursCellCeptMyfenax
Time Corresponding to Occurrence of Cmax (Tmax) of Mycophenolate Mofetil1.119 ± 0.74621.344 ± 1.1439
SecondarySummary of Participants With Adverse Events

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.

Time frame:
Day 1 up to Day 112
Reported as:
Number · participants
Summary of Participants With Adverse Events
participantsCellCeptMyfenaxOverall
Adverse Events151726
Related adverse events379
Severe adverse events000
Adverse events leading to discontinuation213
Serious adverse events111
Adverse events leading to death000

Adverse events

Collected over Day 1 up to Day 112. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
CellCept—1/43 (2.3%)15/43 (34.9%)
Myfenax—1/42 (2.4%)16/42 (38.1%)
Overall—1/43 (2.3%)26/43 (60.5%)
Most frequent serious events
Most frequent serious events
EventCellCeptMyfenaxOverall
Atrial fibrillationCardiac disorders1/431/421/43
Cardiac failureCardiac disorders1/430/421/43
Most frequent other events
Showing 10 of 41
Most frequent other events
EventCellCeptMyfenaxOverall
DiarrhoeaGastrointestinal disorders2/435/426/43
HeadacheNervous system disorders1/433/423/43
Abdominal painGastrointestinal disorders1/432/423/43
NauseaGastrointestinal disorders0/432/422/43
Upper respiratory tract infectionInfections and infestations0/432/422/43
ArthralgiaMusculoskeletal and connective tissue disorders0/432/422/43
Oedema peripheralGeneral disorders2/430/422/43
Herpes simplexInfections and infestations2/430/422/43
NasopharyngitisInfections and infestations2/430/422/43
Blood pressure increasedInvestigations2/430/422/43

Baseline characteristics

Age, Continuous
Age, Continuous(years)Reference/Test/TestTest/Reference/ReferenceTotal
Mean49.7 ± 13.7351.7 ± 13.5550.7 ± 13.52
Sex: Female, Male
Sex: Female, Male(Participants)Reference/Test/TestTest/Reference/ReferenceTotal
Female11819
Male111324
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)Reference/Test/TestTest/Reference/ReferenceTotal
Asian101
Caucasian212142
Height
Height(meters)Reference/Test/TestTest/Reference/ReferenceTotal
Mean1.711 ± 0.10611.718 ± 0.09831.714 ± 0.1012
Weight
Weight(kilograms)Reference/Test/TestTest/Reference/ReferenceTotal
Mean77.19 ± 14.85677.23 ± 15.66177.21 ± 15.072
Body Mass Index
Body Mass Index(kg/m^2)Reference/Test/TestTest/Reference/ReferenceTotal
Mean26.24 ± 3.75625.93 ± 3.42226.09 ± 3.557
08

Study locations

No study locations are listed for this record.

09

References and documents

Publications

  • 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
  • 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. PubMed 22500920 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 8, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00991510
Lead sponsor
Teva Branded Pharmaceutical Products R&D, Inc.
Collaborators
Parexel
Responsible party
Sponsor
First posted
Oct 8, 2009
Start date
Aug 2009
Primary completion
Oct 2010
Completion
Oct 2010
Results posted
Jul 30, 2013
Last update
Nov 8, 2018

Study contacts

Gere Sunder-Plassman, Prof.,MD
principal investigator · Medical University Vienna

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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