CellCept/Iron Study: The Iron Ion-Mycophenolate Mofetil Chelation Complex Interaction in Renal Allograft Recipients

This study has been completed.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by:
University of Michigan
ClinicalTrials.gov Identifier:
NCT00227045
First received: September 23, 2005
Last updated: April 19, 2007
Last verified: April 2007
  Purpose

The objective of this study is to determine the extent and magnitude of the pharmacokinetic drug interaction between mycophenolate mofetil (MFF) (under Css conditions) in the presence of iron in renal transplant recipients.

A two phase pharmacokinetic study will be conducted to determine the bioavailability of MMF (under steady state, Css, conditions) in the presence of two commonly prescribed iron formulations (polysaccharide iron complex and sustained release ferrous sulfate) in renal transplant recipients. This study will evaluate valuable clinical information to help better guide the appropriate utilization of the following formulations and dosing strategies:

  1. Polysaccharide iron complex concomitant administration with MMF,
  2. Sustained release ferrous sulfate concomitant administration with MMF,
  3. Dose separation (2 hours) between MMF and iron (polysaccharide iron complex or sustained release [S.R.] ferrous sulfate)

Condition
End Stage Renal Disease

Study Type: Observational
Study Design: Observational Model: Defined Population
Time Perspective: Cross-Sectional
Official Title: The Iron Ion-Mycophenolate Mofetil Chelation Complex Interaction: A Two Phase Pharmacokinetic Study in Renal Allograft Recipients at the University of Michigan Transplant Program

Resource links provided by NLM:


Further study details as provided by University of Michigan:

Estimated Enrollment: 20
Study Start Date: October 2003
Detailed Description:

Following oral administration, MMF is rapidly absorbed and is presystemically hydrolyzed to its active form MPA in the liver. It is then metabolized by glucuronyl transferase to its inactive metabolite mycophenolic acid glucuronide (MPAG). MPA and MPAG also undergo a significant enterohepatic recirculation process, which is thought to contribute to the secondary peaks in the serum concentrations.

Pharmacokinetic studies in healthy volunteers have demonstrated the bioavailability to be ~94%. Previous studies have shown that many concomitantly administered medications including magnesium and aluminum containing antacids and cholestyramine, significantly impair bioavailability and decrease serum MPA AUCs from 37% and 40%, respectively.

However, of the potentially significant drug interactions involving MMF, iron may have the most clinically significant consequences. A large portion of the transplant population, particularly renal allograft recipients, experience anemia requiring iron supplementation. A single dose pharmacokinetic study conducted in seven healthy volunteers evaluated the effect of concomitant iron (delayed release preparation) administration on the absorption of MMF. This study reported a significant (89.7%) decrease in AUC among patients receiving concomitant iron and MMF. Although this study provides valuable information, it fails to address several clinically pertinent questions for transplant clinicians including:

  1. the potential impact on steady state MPA kinetics in transplant patients,
  2. effect of immediate release iron preparation compared with sustained release iron product, and
  3. the effect of timing of the dose relative to administration of MMF.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients prescribed iron and mycophenolate mofetil concomitantly
  • The subject must be able to give informed consent for the study.
  • Stable renal transplant patients age 18 years and older.
  • At least 6 months status-post primary or secondary kidney transplant.
  • Stable organ function
  • Patients who have achieved therapeutic levels of cyclosporine, tacrolimus, or sirolimus.
  • Patients on stable doses of cyclosporine, tacrolimus, or sirolimus. Defined as: No dosage adjustments within 2 weeks prior to study entry.
  • Patients receiving ferrous sulfate iron preparations (either sustained release or immediate release preparations) or polysaccharide iron complex

Exclusion Criteria:

  • Treated for acute rejection within the last 90 days
  • Received other organ transplants in addition to kidney
  • Pregnant or breast-feeding
  • Use of iron supplements other than ferrous sulfate or polysaccharide iron complex
  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: NCT00227045

Locations
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan
Hoffmann-La Roche
Investigators
Principal Investigator: Jeong Park, PharmD University of Michigan Hospital
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00227045     History of Changes
Other Study ID Numbers: CEL305
Study First Received: September 23, 2005
Last Updated: April 19, 2007
Health Authority: United States: Institutional Review Board

Keywords provided by University of Michigan:
Kidney Transplantation

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Mycophenolate mofetil
Mycophenolic Acid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 28, 2014