Study of Therapeutic Monitoring of Mycophenolate Mofetil (MMF/CellCept) After Kidney Transplantation

NCT00087581 | Completed Phase 4

• 1 other identifier: ML17225
• Study Type: interventional
• Target: 720
• Locations: 1 country
• Sites: 57

Brief Summary

This three-arm study will evaluate the efficacy and safety of various dosing regimens of MMF combined with various dosing regimens of calcineurin inhibitor (CNI), either cyclosporine or tacrolimus, in participants who have undergone kidney transplantation. Participants will be randomized to one of three dosing regimens to receive concentration-controlled MMF with reduced CNI, concentration-controlled MMF with standard CNI, or fixed-dose MMF with standard CNI. Participants will be followed for 20-24 months after randomization.

Conditions

Kidney Transplantation

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants with Treatment Failure During 12 Months Post-Transplantation

  Month 12

• Percent Change from Baseline in Calculated Glomerular Filtration Rate (GFR) at 12 Months Post-Transplantation

  Baseline to Month 12

Secondary Outcomes (10)

• Percentage of Participants with Treatment Failure During 6 and 20-24 Months Post-Transplantation

  Months 6, 20-24

• Percentage of Participants with Biopsy-Proven Acute Rejection (BPAR)

  Months 6, 12, 20-24

• Percentage of Participants by Number of BPAR Episodes

  Months 6, 12, 20-24

• Percentage of Participants Treated for Acute Rejection (AR)

  Months 6, 12, 20-24

• Percentage of Participants Who Experienced Graft Loss

  Months 6, 12, 20-24

Study Arms (3)

Group A: Monitored MMF + Reduced CNI

EXPERIMENTAL

Group A will receive concentration-controlled/monitored MMF with an oral CNI, either cyclosporine or tacrolimus. Depending on body surface area and age, MMF may be given in capsule, tablet, oral suspension, or intravenous (IV) form. The initial dose will be at least 1 gram twice a day (BID) in adults and 600 milligrams per meter-squared (mg/m\^2) in pediatrics. Subsequent doses will be adjusted to maintain blood mycophenolic acid (MPA) levels greater than or equal to (≥) 1.3 micrograms per milliliter (μg/mL) with cyclosporine or ≥1.9 μg/mL with tacrolimus. The selected CNI will be dosed to maintain reduced blood concentrations. Cyclosporine target concentrations are as follows: Days 1-30, 250-325 nanograms per milliliter (ng/mL); Days 30-90, 125-165 ng/mL; Days 90 through end of study, 95-145 ng/mL. Tacrolimus target concentrations areas follows: Days 1-30, 8-12 ng/mL; Days 30-90, 4-6 ng/mL; Days 90 through end of study, 3-5 ng/mL.

Drug: Mycophenolate mofetil; Drug: Cyclosporine; Drug: Tacrolimus

Group B: Monitored MMF + Full CNI

EXPERIMENTAL

Group B will receive concentration-controlled/monitored MMF with an oral CNI, either cyclosporine or tacrolimus. Depending on body surface area and age, MMF may be given in capsule, tablet, oral suspension, or IV form. The initial dose will be at least 1 gram BID in adults and 600 mg/m\^2 in pediatrics. Subsequent doses will be adjusted to maintain blood MPA levels ≥1.3 μg/mL with cyclosporine or ≥1.9 μg/mL with tacrolimus. The selected CNI will be dosed to maintain standard/full blood concentrations. Cyclosporine target concentrations are as follows: Days 1-30, 250-325 ng/mL; Days 30-90, 250-270 ng/mL; Days 90 through end of study, 190-220 ng/mL. Tacrolimus target concentrations are as follows: Days 1-30, 8-12 ng/mL; Days 30-90, 8-10 ng/mL; Days 90 through end of study, 6-8 ng/mL.

Drug: Mycophenolate mofetil; Drug: Cyclosporine; Drug: Tacrolimus

Group C: Fixed MMF + Full CNI

EXPERIMENTAL

Group C will receive fixed-dose MMF with an oral CNI, either cyclosporine or tacrolimus. Depending on body surface area and age, MMF may be given in capsule, tablet, oral suspension, or IV form. The dose will be at least 1 gram BID in adults and 600 mg/m\^2 in pediatrics. Subsequent doses are not to be adjusted, except in the case of unacceptable toxicity. The selected CNI will be dosed to maintain standard/full blood concentrations. Cyclosporine target concentrations are as follows: Days 1-30, 250-325 ng/mL; Days 30-90, 250-270 ng/mL; Days 90 through end of study, 190-220 ng/mL. Tacrolimus target concentrations are as follows: Days 1-30, 8-12 ng/mL; Days 30-90, 8-10 ng/mL; Days 90 through end of study, 6-8 ng/mL.

Drug: Mycophenolate mofetil; Drug: Cyclosporine; Drug: Tacrolimus

Interventions

Mycophenolate mofetil DRUG

Depending on body surface area and age, MMF may be given in capsule, tablet, oral suspension, or IV form. The initial dose will be at least 1 gram BID in adults and 600 mg/m\^2 in pediatrics. In Groups A and B, subsequent doses will be adjusted to maintain blood MPA levels ≥1.3 μg/mL with cyclosporine or ≥1.9 μg/mL with tacrolimus. In Group C, subsequent doses are not to be adjusted, except in the case of unacceptable toxicity.

Also known as: CellCept

Group A: Monitored MMF + Reduced CNI; Group B: Monitored MMF + Full CNI; Group C: Fixed MMF + Full CNI

Cyclosporine DRUG

Cyclosporine will be given as 100-mg soft gelatin capsules and dosed to maintain either reduced (Group A) or standard/full (Groups B and C) blood concentrations. Cyclosporine target concentrations are as follows: Days 1-30, 250-325 ng/mL; Days 30-90, 125-165 ng/mL (reduced) or 250-270 ng/mL (full); Days 90 through end of study, 95-145 ng/mL (reduced) or 190-220 ng/mL (full).

Also known as: Neoral

Group A: Monitored MMF + Reduced CNI; Group B: Monitored MMF + Full CNI; Group C: Fixed MMF + Full CNI

Tacrolimus DRUG

Tacrolimus will be given as 1-mg and 5-mg capsules and dosed to maintain either reduced (Group A) or standard/full (Groups B and C) blood concentrations. Tacrolimus target concentrations are as follows: Days 1-30, 8-12 ng/mL; Days 30-90, 4-6 ng/mL (reduced), 8-10 ng/mL (full); Days 90 through end of study, 3-5 ng/mL (reduced), 6-8 ng/mL (full).

Also known as: Prograf

Group A: Monitored MMF + Reduced CNI; Group B: Monitored MMF + Full CNI; Group C: Fixed MMF + Full CNI

Eligibility Criteria

• Age: 13 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Males or females 13-75 years of age
• Single organ recipient (kidney only) from living (related or unrelated) or cadaveric heart-beating donors
• Receiving first or second kidney transplant

You may not qualify if:

• Immunosuppressive therapy (except for 48 hours prior to transplantation and corticosteroid treatment) within previous 28 days for a first transplant and 3 months for a second transplant
• History of malignancy in last 5 years (except successfully treated localized non-melanoma skin cancer)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (57)

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Birmingham, Alabama, 35294, United States

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Little Rock, Arkansas, 72205, United States

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Bakersfield, California, 93309, United States

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Los Angeles, California, 90048, United States

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Los Angeles, California, 90057, United States

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San Francisco, California, 94143-0116, United States

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Denver, Colorado, 80262, United States

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Gainesville, Florida, 32610-0224, United States

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Jacksonville, Florida, 32216, United States

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Miami, Florida, 33101, United States

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Orlando, Florida, 32804, United States

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Tampa, Florida, 33606, United States

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Augusta, Georgia, 30912, United States

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Chicago, Illinois, 60637, United States

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Indianapolis, Indiana, 46202-5124, United States

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Wichita, Kansas, 67214, United States

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Lexington, Kentucky, 40536-0293, United States

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New Orleans, Louisiana, 70121, United States

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Shreveport, Louisiana, 71130, United States

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Baltimore, Maryland, 21287-8611, United States

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Boston, Massachusetts, 02111, United States

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Boston, Massachusetts, 02215, United States

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Burlington, Massachusetts, 01805, United States

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Springfield, Massachusetts, 01107, United States

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Worcester, Massachusetts, 01655, United States

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Ann Arbor, Michigan, 48109-0362, United States

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Detroit, Michigan, 48202-2689, United States

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Rochester, Minnesota, 55905, United States

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Hackensack, New Jersey, 07601, United States

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Livingston, New Jersey, 07039, United States

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Buffalo, New York, 14203, United States

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Hawthorne, New York, 10532, United States

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New York, New York, 10021, United States

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New York, New York, 10029, United States

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New York, New York, 10032, United States

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Rochester, New York, 14642-8410, United States

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The Bronx, New York, 10467, United States

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Chapel Hill, North Carolina, 27599, United States

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Winston-Salem, North Carolina, 27157, United States

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Fargo, North Dakota, 58122, United States

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Cleveland, Ohio, 44106, United States

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Portland, Oregon, 97210, United States

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Harrisburg, Pennsylvania, 17101, United States

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Hershey, Pennsylvania, 17033, United States

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Philadelphia, Pennsylvania, 19102-1192, United States

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Philadelphia, Pennsylvania, 19104, United States

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Philadelphia, Pennsylvania, 19140, United States

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Pittsburgh, Pennsylvania, 15212, United States

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Providence, Rhode Island, 02903, United States

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Dallas, Texas, 75246, United States

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San Antonio, Texas, 78284, United States

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Salt Lake City, Utah, 84132, United States

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Burlington, Vermont, 05401, United States

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Falls Church, Virginia, 22042-3300, United States

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Norfolk, Virginia, 23502, United States

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Seattle, Washington, 98104, United States

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Madison, Wisconsin, 53792, United States

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MeSH Terms

Interventions

Mycophenolic Acid; Cyclosporine; Tacrolimus

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Macrolides; Lactones

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: July 12, 2004
• First Posted: July 14, 2004
• Study Start: June 1, 2004
• Primary Completion: September 1, 2007
• Study Completion: September 1, 2007
• Last Updated: November 7, 2016

Record last verified: 2016-09

Locations

US (57)