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

NCT00991510 | Terminated Phase 4 Results

• 2 other identifiers: 116B82009-010562-31
• Study Type: interventional
• Target: 43
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Stable Renal Transplant Recipients

Keywords

renal transplantation; mycophenolate mofetil; pharmacokinetics; immunosuppression

Outcome Measures

Primary Outcomes (3)

• 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).

  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.

  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.

  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

  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)

  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)

  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

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

• Summary of Participants With Adverse Events

  Day 1 up to Day 112

Study Arms (2)

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.

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.

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

Interventions

mycophenolate mofetil (Myfenax) DRUG

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®

Reference/Test/Test; Test/Reference/Reference

mycophenolate mofetil (Cellcept) DRUG

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®

Reference/Test/Test; Test/Reference/Reference

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead
• Parexel: collaborator

Related Publications (2)

• 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

  RESULT

• 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.

  PMID: 22500920 RESULT

MeSH Terms

Interventions

Mycophenolic Acid

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

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.

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc.

ustevatrials@tevapharm.com

215-591-3000

Study Officials

• Gere Sunder-Plassman, Prof.,MD

  Medical University Vienna

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 29, 2009
• First Posted: October 8, 2009
• Study Start: August 1, 2009
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: November 8, 2018
• Results First Posted: July 30, 2013

Record last verified: 2018-10