Stable Renal Transplant RecipientsPhase 4NCT00991510

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

A Phase 4 study testing mycophenolate mofetil (Myfenax) and mycophenolate mofetil (Cellcept) in people with Stable Renal Transplant Recipients, run by Teva Branded Pharmaceutical Products R&D, Inc..

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Stable Renal Transplant Recipients
What is being tested?: mycophenolate mofetil (Myfenax) and mycophenolate mofetil (Cellcept)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 43 participants
Where: No sites listed yet
Study dates: Aug 2009to Oct 2010
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Show all 21Show fewer

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.

About this study

Official title: Comparative Bioavailability of Myfenax® (Teva) and CellCept® (Roche) in Stable Patients After Renal Transplantation

Conditions: Stable Renal Transplant Recipients
Being tested: mycophenolate mofetil (Myfenax), mycophenolate mofetil (Cellcept)
Keywords: renal transplantation, mycophenolate mofetil, pharmacokinetics, immunosuppression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

mycophenolate mofetil (Myfenax)Drug
Also called 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.
mycophenolate mofetil (Cellcept)Drug
Also called 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.

Study groups in NCT00991510
Study group	Role	What they receive
Reference/Test/Test	Experimental	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. Receives: Drug: mycophenolate mofetil (Myfenax); Drug: mycophenolate mofetil (Cellcept)
Test/Reference/Reference	Experimental	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. Receives: Drug: mycophenolate mofetil (Myfenax); Drug: mycophenolate mofetil (Cellcept)

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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 (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.
Measured: 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
Maximum Observed Plasma Concentration (Cmax) of Mycophenolate Mofetil
Cmax was directly obtained from measured values of plasma concentrations.
Measured: 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 (5)

Minimum Observed Plasma Concentration (Cmin) of Mycophenolate Mofetil
Cmin was directly obtained from measured values of plasma concentrations.
Measured: 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
Plasma Concentrations of Mycophenolate Mofetil in Pre-Administration Samples (Cpd)
Cpd was directly obtained from measured values of plasma concentrations.
Measured: Day 14 and Day 28 (end of first two cross-over periods) before drug administration
Degree of Fluctuation of the Concentration Levels of Mycophenolate Mofetil Over One Dosing Interval (PTF)
PTF was calculated as: (Cmax-Cmin)/(AUCt/t)*100
Measured: Day 14 and Day 28 (end of first two cross-over periods) before drug administration
Time Corresponding to Occurrence of Cmax (Tmax) of Mycophenolate Mofetil
Tmax was directly obtained from measured values.
Measured: Day 14 and Day 28 (end of first two cross-over periods) before drug administration
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.
Measured: Day 1 up to Day 112

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2009Oct 2010

First posted8 Oct 2009 (estimated)
Study startAug 2009
Primary completionOct 2010
Study completionOct 2010

Why it stopped: Slow recruitment and lack of time to product launch

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Stable Renal Transplant RecipientsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 43 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00991510
Sponsor's protocol ID: 116B8
Other IDs: 2009-010562-31, 2009
Status last verified: Oct 2018
First submitted: 29 Aug 2009
Last updated: 8 Nov 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

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

Study at a glance

From the registry record, last updated by the sponsor on 8 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Comparative Bioavailability of Myfenax® (Teva) and CellCept® (Roche) in Stable Patients After Renal Transplantation
ClinicalTrials.gov ID: NCT00991510
Acronym / sponsor ID: 116B8
Conditions: Stable Renal Transplant Recipients
Keywords: renal transplantation, mycophenolate mofetil, pharmacokinetics, immunosuppression
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: Slow recruitment and lack of time to product launch
Enrolment: 43 participants (actual)
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.Industry (pharma, biotech, devices)
Collaborators: Parexel
Study start: Aug 2009
Primary completion: Oct 2010 (actual)
Study completion: Oct 2010 (actual)
First posted: 8 Oct 2009 (estimated)
Results: Posted 30 Jul 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Reference/Test/Test	Experimental	Drug: mycophenolate mofetil (Myfenax), Drug: 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	Experimental	Drug: mycophenolate mofetil (Myfenax), Drug: 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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.

Key exclusion criteria (21 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
mycophenolate mofetil (Myfenax)Also: 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.	Drug	Reference/Test/Test, Test/Reference/Reference
mycophenolate mofetil (Cellcept)Also: 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.	Drug	Reference/Test/Test, Test/Reference/Reference

Primary outcome

Area Under the Plasma Concentration-time Curve (AUC(0-6h)) of Mycophenolate Mofetil
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
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).
Area Under the Plasma Concentration-time Curve (AUC(0-tau)) of Mycophenolate Mofetil
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
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.
Maximum Observed Plasma Concentration (Cmax) of Mycophenolate Mofetil
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
Cmax was directly obtained from measured values of plasma concentrations.

5 secondary outcomes

Minimum Observed Plasma Concentration (Cmin) of Mycophenolate Mofetil
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
Plasma Concentrations of Mycophenolate Mofetil in Pre-Administration Samples (Cpd)
Time frame: Day 14 and Day 28 (end of first two cross-over periods) before drug administration
Degree of Fluctuation of the Concentration Levels of Mycophenolate Mofetil Over One Dosing Interval (PTF)
Time frame: Day 14 and Day 28 (end of first two cross-over periods) before drug administration
Time Corresponding to Occurrence of Cmax (Tmax) of Mycophenolate Mofetil
Time frame: Day 14 and Day 28 (end of first two cross-over periods) before drug administration
Summary of Participants With Adverse Events
Time frame: Day 1 up to Day 112

Results and safety

Results posted to the registry on 30 Jul 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Reference/Test/Test	22	21
Test/Reference/Reference	21	21

Primary outcome: Area Under the Plasma Concentration-time Curve (AUC(0-6h)) of Mycophenolate Mofetil

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. Mean (Standard Deviation). Unit: hour* µg /ml

Measure	CellCept n = 41	Myfenax n = 41
Value	33.523 (15.1265)	31.100 (15.4198)

CellCept vs Myfenax: adjusted least-squares mean ratio: 0.923 (90% CI 0.865 to 0.984), ANOVA

Population analysed: PK population. Two participants were excluded from the PK population: one dropped out of the study during the first period so had no PK samples. The other was omitted due to protocol violations.

Primary outcome: Area Under the Plasma Concentration-time Curve (AUC(0-tau)) of Mycophenolate Mofetil

Measure	CellCept n = 41	Myfenax n = 41
Value	49.846 (20.8278)	48.255 (21.2246)

CellCept vs Myfenax: adjusted least-squares mean ratio: 0.959 (90% CI 0.899 to 1.023), ANOVA

Primary outcome: Maximum Observed Plasma Concentration (Cmax) of Mycophenolate Mofetil

Measure	CellCept n = 41	Myfenax n = 41
Value	16.189 (9.9448)	14.308 (8.3432)

CellCept vs Myfenax: adjusted least-squares mean ratio: 0.873 (90% CI 0.787 to 0.968), ANOVA

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: Day 1 up to Day 112. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CellCept	1 of 43 (2.3%)	15 of 43 (34.9%)	Not reported
Myfenax	1 of 42 (2.4%)	16 of 42 (38.1%)	Not reported
Overall	1 of 43 (2.3%)	26 of 43 (60.5%)	Not reported

Limitations and caveats (from the sponsor): The study was designed to have a power of at least 80 % to show bioequivalence with 80 subjects. Only 43 subjects were included.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publicationSunder-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
Results publication: PubMed 22500920Sunder-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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Gere Sunder-Plassman, Prof.,MD principal investigator

Medical University of Vienna

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing mycophenolate mofetil (Myfenax) and mycophenolate mofetil (Cellcept) in people with Stable Renal Transplant Recipients, run by Teva Branded Pharmaceutical Products R&D, Inc..

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jul 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Plasma Concentration-time Curve (AUC(0-6h)) of Mycophenolate Mofetil (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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00991510, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2018.