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

This study has been completed.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:
NCT00281619
First received: January 23, 2006
Last updated: December 18, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Kidney Transplant
Drug: CellCept (mycophenolate mofetil)
Behavioral: Dietary Monitoring
Behavioral: Drug Diary
Procedure: Blood Sampling
Phase 1

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Development of Population Pharmacokinetic-Pharmacodynamic (PK-PD) Models of Mycophenolic Acid for Bayesian Dose Individualization in Pediatric Kidney Transplant Patients

Resource links provided by NLM:


Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:
  • 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): [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Drug Measurement of MPA and MPA-G [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • IMPDH Assay [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Mitogenesis Assays and [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Determination of CD25 Expression. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Concomitant medications and MPA (CellCept) drug diary (study visits 1-4) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Physical Exam (study visits 1-4) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Safety Laboratory tests (study visits 1-4) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Dietary Monitoring (study visits 2,3 & 4) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Adverse Event Reporting (study visits 1-4). [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Enrollment: 29
Study Start Date: January 2006
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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) Behavioral: Dietary Monitoring Behavioral: Drug Diary Procedure: Blood Sampling

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.

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

Criteria

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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00281619

Locations
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Hoffmann-La Roche
Investigators
Principal Investigator: Alexander A. Vinks, PharmD., PhD Children's Hospital Medical Center, Cincinnati
  More Information

No publications provided

Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT00281619     History of Changes
Other Study ID Numbers: CEL420 MPA (PK-PD), CEL420
Study First Received: January 23, 2006
Last Updated: December 18, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Hospital Medical Center, Cincinnati:
Pediatric Kidney Transplant
Kidney Transplant
CellCept
Mycophenolate mofetil
Mycophenolic Acid
MPA

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

ClinicalTrials.gov processed this record on April 16, 2014