MPA PK Monitoring Strategy With MMF/FK Based Immunosuppression

This study has been completed.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
University of Florida
ClinicalTrials.gov Identifier:
NCT00187941
First received: September 13, 2005
Last updated: June 19, 2012
Last verified: June 2012
  Purpose

Individuals absorb Cellcept (MMF/Mycophenolate Mofetil) at different rates and it is difficult to determine an individuals level of Mycophenolate Mofetil (MMF, trade name Cellcept)from a single measurement. We will enroll 20 subjects. Plasma samples to be collected pre-MMF dose (trough level) and at 30 and 120 min after the morning dose of MMF.This will be done weekly for the first month and then monthly for the next 6 mths. We hope to use a calculation of the subjects total MMF level during the first month to set a trough target level to use during the next 6 months.


Condition Intervention Phase
Transplantation, Renal
Immunosuppression
Drug: Mycophenolate Mofetil
Phase 0

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Trial for Implementation of a Medroxyprogesterone(MPA)Pharmacokinetic(PK) Monitoring Strategy in Patients on Mycophenolate Mofetil(MMF)/FK Based Immunosuppression.

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Proportion of patients whose measured AUC falls within or outside the therapeutic MPA target range (30-60 mg/L/h) at any given follow up interval, as average over the whole time period. [ Time Frame: 7 months ] [ Designated as safety issue: No ]
  • Proportion of patients achieving one or more therapeutic level AUC. [ Time Frame: 7 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of acute rejection of transplanted kidney [ Time Frame: 7 months ] [ Designated as safety issue: Yes ]
  • Incidence of potentially MPA related toxicities [ Time Frame: 7 months ] [ Designated as safety issue: Yes ]
  • Number of dose changes needed to achieve MPA AUC target within the first month post-transplant [ Time Frame: 1 months ] [ Designated as safety issue: No ]
  • Number of dose changes needed to achieve the individualized MPA trough target levels following the first month. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To obtain 20 to 25 intraindividual correlation estimates (of one type or another) within each patient: trough vs. AUC. [ Time Frame: 7 months ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: August 2005
Study Completion Date: November 2006
Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
CellCept
CellCept + Prograf or Neoral + Steroids
Drug: Mycophenolate Mofetil
Targeted MPA exposure to 30-60 mg/L/h during the first month post-transplant.
Other Names:
  • CellCept
  • MMF
  • RO 70-0003

Detailed Description:

We would use repeated Areas-Under-the-Curve (AUC-a statistical means of summarizing information from a series of measurements on one individual) during the first month post transplant to establish a therapeutic drug exposure for each single patient. We would use the individual trough level from each individual therapeutic AUC for a subsequent individual trough target range. For the purpose of the study, in order to show that by targeting these individualized Mycophenolic Acid (MPA) trough levels we effectively are keeping the patients within a therapeutic drug exposure range, we would continue to obtain abbreviated AUC's at follow up visits. The investigator would be blind to the results of these AUC's after the first month after transplant in order to allow drug exposure targeting only by trough measurements.

From 4 days post transplant, we would draw blood for abbreviated AUC's at 4-5 subsequent clinic visits within a 4 week time frame. We would change the dose based on each AUC to establish an MPA target exposure above 30 mg/L. The individual trough level corresponding to the each patients AUC on target is going to be used for subsequent pk (pharmacokinetic) monitoring. For example if a patient is on 1250 mg bid of Cellcept and we finally obtain an AUC of 40 mg/L/hr and the trough concentration at the time of this pk profile is 2.5 mg/L, we would subsequently target this patient's trough level above 2.5 mg/L. The subsequent AUC's (only needed for the study, not for the final monitoring strategy once established) would serve to confirm that by targeting the trough above 2.5 mg/L the patient effectively stayed within the AUC target range of 30-60 mg/L.

The investigator would be blinded to the follow up AUC's after the first month because the primary objective of the study is to determine if by trough level targeting therapeutic exposure as measured by AUC can be achieved. The investigators would not be blinded though to the initial AUC's which are used to get the patient initially into a therapeutic target window.

We would not consider dose reductions based on elevated trough levels unless toxicities were present. On the other hand we would act on low levels with dose increases in 250 mg bid increments.

For this study we would propose 20 subjects to be enrolled. Each patient would undergo abbreviated pk sampling 4-5 times between week 1 to 4. Subsequently we would do abbreviated AUC's monthly until month 7. We would enroll all patients including those presenting with slow graft function or delayed graft function except for those patients with early technical failure.

Therefore for the study each patient would undergo approximately 12 abbreviated AUC's in the first 7 month's post transplant. Drop out patients will be replaced by new recruits to obtain an evaluable number of patients.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female, age 18-80
  • On Cellcept (MMF) and Prograf (tacrolimus) based immunosuppression
  • Recipient of cadaveric or living donated kidney transplants

Exclusion Criteria:

  • Documented non-compliance prior transplant
  • Serum albumin <2.5 mg/dl
  • Primary non-function
  • Not on Prograf
  • Pregnant females
  • Active serious digestive system disorder
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00187941

Locations
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
Sponsors and Collaborators
University of Florida
Hoffmann-La Roche
Investigators
Principal Investigator: Herwig-Ulf Meier-Kriesche, MD University of Florida
  More Information

No publications provided

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT00187941     History of Changes
Other Study ID Numbers: CEL470
Study First Received: September 13, 2005
Last Updated: June 19, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of Florida:
transplant
renal
Cellcept
therapeutic drug level
MMF
MPA
immunosuppression

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

ClinicalTrials.gov processed this record on July 23, 2014