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.

Study Overview

• Status: Completed
• Conditions: Kidney Transplant
• Intervention / Treatment: Drug: CellCept (mycophenolate mofetil); Procedure: Blood Sampling; Behavioral: Dietary Monitoring; Behavioral: Drug Diary

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 29

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Male subjects and non-pregnant female subjects aged 2-17 years who are about to receive a kidney transplant and will be on post transplant MMF containing immunosuppressive therapy, per clinical care.

Description

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).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Mycophenolic Acid (CellCept); 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	Drug: CellCept (mycophenolate mofetil); Procedure: Blood Sampling; Behavioral: Dietary Monitoring; Behavioral: Drug Diary

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The following outcome measures will be performed at study visit 2 (2-3 days post-transplant), study visit 3 (6-9 days post-transplant), and study visit 4 (3-6 months post-transplant):	6 months
Drug Measurement of MPA and MPA-G	6 months
IMPDH Assay	6 months
Mitogenesis Assays and	6 months
Determination of CD25 Expression.	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Concomitant medications and MPA (CellCept) drug diary (study visits 1-4)	6 months
Physical Exam (study visits 1-4)	6 months
Safety Laboratory tests (study visits 1-4)	6 months
Dietary Monitoring (study visits 2,3 & 4)	6 months
Adverse Event Reporting (study visits 1-4).	6 months

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: Hoffmann-La Roche
• Investigators: Principal Investigator: Alexander A. Vinks, PharmD., PhD, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start: January 1, 2006
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: January 23, 2006
• First Submitted That Met QC Criteria: January 23, 2006
• First Posted (Estimate): January 25, 2006

Study Record Updates

• Last Update Posted (Estimate): December 19, 2013
• Last Update Submitted That Met QC Criteria: December 18, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Kidney Transplant; Mycophenolate mofetil; MPA; CellCept; Mycophenolic Acid; Pediatric Kidney Transplant
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Mycophenolic Acid
• Other Study ID Numbers: CEL420 MPA (PK-PD); CEL420