Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00087581
First received: July 12, 2004
Last updated: November 3, 2016
Last verified: September 2016
  Purpose
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.

Condition Intervention Phase
Kidney Transplantation
Drug: Mycophenolate mofetil
Drug: Cyclosporine
Drug: Tacrolimus
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Prospective, Randomized, Controlled, Multi-Center Study Assessing Fixed Dose Versus Concentration Controlled Cellcept® Regimens for Patients Following a Single Organ Renal Transplantation in Combination With Full Dose and Reduced Dose Calcineurin Inhibitors

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants with Treatment Failure During 12 Months Post-Transplantation [ Time Frame: Month 12 ] [ Designated as safety issue: No ]
  • Percent Change from Baseline in Calculated Glomerular Filtration Rate (GFR) at 12 Months Post-Transplantation [ Time Frame: Baseline to Month 12 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of Participants with Treatment Failure During 6 and 20-24 Months Post-Transplantation [ Time Frame: Months 6, 20-24 ] [ Designated as safety issue: No ]
  • Percentage of Participants with Biopsy-Proven Acute Rejection (BPAR) [ Time Frame: Months 6, 12, 20-24 ] [ Designated as safety issue: No ]
  • Percentage of Participants by Number of BPAR Episodes [ Time Frame: Months 6, 12, 20-24 ] [ Designated as safety issue: No ]
  • Percentage of Participants Treated for Acute Rejection (AR) [ Time Frame: Months 6, 12, 20-24 ] [ Designated as safety issue: No ]
  • Percentage of Participants Who Experienced Graft Loss [ Time Frame: Months 6, 12, 20-24 ] [ Designated as safety issue: No ]
  • Percentage of Participants Who Died [ Time Frame: Months 6, 12, 20-24 ] [ Designated as safety issue: No ]
  • Percentage of Participants Who Discontinued Treatment with MMF [ Time Frame: Months 6, 12, 20-24 ] [ Designated as safety issue: No ]
  • Time to First BPAR Episode [ Time Frame: Months 6, 12, 20-24 ] [ Designated as safety issue: No ]
  • Time to Treatment Failure [ Time Frame: Months 6, 12, 20-24 ] [ Designated as safety issue: No ]
  • Percent Change from Baseline in Calculated GFR at 3, 6, and 20-24 Months Post-Transplantation [ Time Frame: Baseline to Months 3, 6, 20-24 ] [ Designated as safety issue: No ]

Enrollment: 720
Study Start Date: June 2004
Study Completion Date: September 2007
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group A: Monitored MMF + Reduced CNI
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
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.
Other Name: CellCept
Drug: Cyclosporine
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).
Other Name: Neoral
Drug: Tacrolimus
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).
Other Name: Prograf
Experimental: Group B: Monitored MMF + Full CNI
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
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.
Other Name: CellCept
Drug: Cyclosporine
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).
Other Name: Neoral
Drug: Tacrolimus
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).
Other Name: Prograf
Experimental: Group C: Fixed MMF + Full CNI
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
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.
Other Name: CellCept
Drug: Cyclosporine
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).
Other Name: Neoral
Drug: Tacrolimus
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).
Other Name: Prograf

  Eligibility

Ages Eligible for Study:   13 Years to 75 Years   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00087581

  Show 57 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00087581     History of Changes
Other Study ID Numbers: ML17225 
Study First Received: July 12, 2004
Last Updated: November 3, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Tacrolimus
Cyclosporins
Cyclosporine
Mycophenolate mofetil
Calcineurin Inhibitors
Mycophenolic Acid
Benzocaine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Sensory System Agents
Peripheral Nervous System Agents
Antibiotics, Antineoplastic
Antineoplastic Agents

ClinicalTrials.gov processed this record on December 02, 2016