PK-PD Study of Mycophenolic Acid (CellCept) in Pediatric Kidney Transplant Patients

Development of Population Pharmacokinetic-Pharmacodynamic (PK-PD) Models of Mycophenolic Acid for Bayesian Dose Individualization in Pediatric Kidney Transplant Patients

The purpose of this study is to determine how fast children, who have had a recent kidney transplant, absorb, breakdown and eliminate mycophenolic acid (CellCept) following their prescribed dose. The results may lead to better dosing based on individual needs.

This is an open-label, inpatient-outpatient population pharmacokinetic-pharmacodynamic (PK-PD) study of mycophenolic acid (MPA) in pediatric subjects (age 2-17 years) who have had a recent kidney transplant, as well as during the stable renal transplant period when on a stable oral regimen of MPA. The primary objective of this study is to develop population pharmacokinetic-pharmacodynamic (PK-PD) models for mycophenolic acid (MPA) and mycophenolic acid glucuronide (MPAG) in order to improve individualized pediatric dosing. Subjects will have been receiving CellCept as part of their clinical standard of care. It is anticipated that the clinical portion of the study for each patient will be approximately six months post renal transplant with four study days: a screening visit pre-transplant, two 10-hour inpatient days at 2-3 and 6-9 days post-transplant, and one (up to 10 hour) outpatient visit at 3-6 months post-transplant. Pharmacokinetic and pharmacodynamic measurements will be conducted at various time points (up to 9 hours post dose) on study days 2, 3, and 4. Safety data to be collected will include physical examinations, measurement of vital signs, and laboratory assessments, as well as data on adverse events and clinical outcomes.

Inclusion Criteria:

• Male subjects and non-pregnant female subjects aged 2 to 17 years who are about to receive a kidney transplant and will be on post transplant MMF containing immunosuppressive therapy. Subjects may be enrolled up to their 18th year.
• Minimum weight of 11 kg.
• A signed and dated IRB approved parental / guardian informed consent form and an IRB-approved child assent form if applicable.
• A high probability for compliance with and completion of the study.
• For post-transplant study period: Subjects with stable kidney allografts who are at least 3 months post-transplant and who have received the same regimen of MMF (with cyclosporine or tacrolimus) for at least 30 days before the study visit (3-6 months post-transplant).
• May have clinically important abnormalities on clinical and /or laboratory evaluations only as these abnormalities relate to an underlying condition as determined by the principal investigator.
• Other variations from established normal ranges may be acceptable if they are not clinically significant in the opinion of the investigators.

Exclusion Criteria:

• Any medical condition (active or chronic) or prior surgery that may interfere with the pharmacokinetic behavior of MMF (absorption, distribution and elimination) as determined by the PI.
• Active systemic infection.
• History of substance abuse.
• Signs or symptoms of active hepatitis (a history of hepatitis B or C virus infection is permitted).
• Known history of or suspected infection with human immunodeficiency virus (HIV).