- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00187941
MPA PK Monitoring Strategy With MMF/FK Based Immunosuppression
Pilot Trial for Implementation of a Medroxyprogesterone(MPA)Pharmacokinetic(PK) Monitoring Strategy in Patients on Mycophenolate Mofetil(MMF)/FK Based Immunosuppression.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
-
-
Florida
-
Gainesville, Florida, United States, 32610
- University of Florida
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
OTHER: CellCept
CellCept + Prograf or Neoral + Steroids
|
Targeted MPA exposure to 30-60 mg/L/h during the first month post-transplant.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
7 months
|
Proportion of patients achieving one or more therapeutic level AUC.
Time Frame: 7 months
|
7 months
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Incidence of acute rejection of transplanted kidney
Time Frame: 7 months
|
7 months
|
Incidence of potentially MPA related toxicities
Time Frame: 7 months
|
7 months
|
Number of dose changes needed to achieve MPA AUC target within the first month post-transplant
Time Frame: 1 months
|
1 months
|
Number of dose changes needed to achieve the individualized MPA trough target levels following the first month.
Time Frame: 6 months
|
6 months
|
To obtain 20 to 25 intraindividual correlation estimates (of one type or another) within each patient: trough vs. AUC.
Time Frame: 7 months
|
7 months
|
Collaborators and Investigators
Sponsor
Collaborators
Publications and helpful links
General Publications
- Guerra G, Srinivas TR, Schold JD, Eagan AE, Nawrocki, Shaw L, Kaplan B, Womer K, Meier-Kriesche HU. Prospective Blinded Pharmacokinetic Trial to Establish an Individualized MPA Trough Regimen. American Transplant Congress, San Francisco, California
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CEL470
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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