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

Kidney Transplant Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00281619
• Other study ID #: CEL420 MPA (PK-PD)
• Secondary ID: CEL420
• Status: Completed
• Phase: Phase 1
• First received: January 23, 2006
• Last updated: December 18, 2013
• Start date: January 2006
• Est. completion date: February 2010

Study information

• Verified date: December 2013
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 17 Years

Eligibility

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 Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Kidney Transplant

Intervention

Drug:
• CellCept (mycophenolate mofetil)

Behavioral:
• Dietary Monitoring

• Drug Diary

Procedure:
• Blood Sampling

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	Drug Measurement of MPA and MPA-G		6 months	Yes
Primary	IMPDH Assay		6 months	Yes
Primary	Mitogenesis Assays and		6 months	Yes
Primary	Determination of CD25 Expression.		6 months	Yes
Secondary	Concomitant medications and MPA (CellCept) drug diary (study visits 1-4)		6 months	Yes
Secondary	Physical Exam (study visits 1-4)		6 months	Yes
Secondary	Safety Laboratory tests (study visits 1-4)		6 months	Yes
Secondary	Dietary Monitoring (study visits 2,3 & 4)		6 months	No
Secondary	Adverse Event Reporting (study visits 1-4).		6 months	Yes