Genetic Drug Study of Mycophenolic Acid (CellCept) in Pediatric Kidney Transplant Patients

Kidney Transplant Clinical Trial

Official title:

Pharmacogenetics of Mycophenolic Acid in Kidney Transplant Patients

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00433953
• Other study ID #: 06-06-44
• Status: Terminated
• Phase: Phase 1
• First received: February 8, 2007
• Last updated: February 18, 2013
• Start date: February 2007
• Est. completion date: February 2010

Study information

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

Clinical Trial Summary

The purpose of this study is to determine how genes influence the response to mycophenolate mofetil (CellCept) in children who have had a kidney transplant. The study will look at how differences in some genes effect blood levels of mycophenolate mofetil over time in children, how often side effects occur and the way that children respond to mycophenolate mofetil.

The results may lead to better dosing based on individual needs.

Description:

This is an open label, inpatient-outpatient prospective observational study to determine whether the inter-patient variability in mycophenolic acid (MPA) pharmacokinetics and exposure, adverse events and clinical response in pediatric transplant patients (ages 2-18 years) is associated with identifiable pharmacogenetic factors. Specific aims: 1.) To determine whether common polymorphic variations in the uridine diphosphate-glucuronosyltransferases (UGTs) are associated with inter-individual variability in MPA pharmacokinetics and exposure (by affecting MPA metabolism). 2.) To determine whether common polymorphic variations in the uridine diphosphate-glucuronosyltransferases (UGTs) are associated with inter-patient differences in the incidence of adverse events (by affecting the formation of the acyl-glucuronide metabolite). Enrolled subjects will have been receiving mycophenolate mofetil as part of their clinical standard of care. It is anticipated that the clinical portion of the study will last up to 4 hours at one study visit to include one pharmacogenetic blood sample and 4 pharmacokinetic blood samples collected out to 3 hours post-dose. Safety data to be collected will include standard of care physical exam and safety laboratory tests as well as data on adverse events and clinical outcomes.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 44
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 18 Years

Eligibility

Inclusion Criteria:

• Male subjects and non-pregnant female subjects aged 2 to 18 years who are about to receive a kidney transplant and will be on post transplant MMF containing immunosuppressive therapy.

• A signed and dated institutional review board (IRB) approved parental/guardian informed consent form and an IRB approved child assent form if applicable.

• Subjects with stable kidney allografts who are on a stable regimen of MMF (with tacrolimus and steroids)

• 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.

Exclusion Criteria:

• Children receiving cyclosporine therapy that may interact with MPA entero-hepatic recycling.

• Any medical condition(active or chronic) or prior surgery that may interfere with the pharmacokinetics of MMF as determined by the principal investigator.

• Concomitant medication that may interfere with the pharmacokinetics of MMF as determined by the principal investigator.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kidney Transplant

Intervention

Drug:
• Mycophenolate Mofetil (CellCept)

Behavioral:
• Dietary Monitoring

• Drug Diary

Procedure:
• Blood Sampling

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

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 the study visit after the patient is on a steady state dose of mycophenolate mofetil:		Day 1	No
Primary	Drug measurement of MPA, MPA-G and acyl-MPA-G		Day 1	No
Primary	Genomic DNA extraction using standard procedures. Patients will be genotyped for the UGT2B7, UGT1A8, UGT1A9 polymorphism.		Day 1	No
Secondary	Concomitant medications and mycophenolate mofetil drug diary		Day 1	No
Secondary	Physical Exam		Day 1	Yes
Secondary	Safety Laboratory tests		Day 1	Yes
Secondary	Dietary Monitoring		Day 1	No
Secondary	Adverse Event Reporting		Day 1	Yes