MPA PK Monitoring Strategy With MMF/FK Based Immunosuppression
Condition: Transplantation, Renal; Immunosuppression
Study type: Interventional
Phase: Early Phase 1

Summary: 
      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.
    

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.
    

Intervention name(s): Mycophenolate Mofetil
Intervention type(s): Drug
Intervention description(s): Targeted MPA exposure to 30-60 mg/L/h during the first month post-transplant.
Other intervention name(s): CellCept; MMF; RO 70-0003
Intervention MeSH terms: Mycophenolic Acid
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: transplant; renal; Cellcept; therapeutic drug level; MMF; MPA; immunosuppression