Pharmacokinetics of Mmf and Valganciclovir

Kidney Transplant Recipient Clinical Trial

Official title:

Pharmacokinetics of Mycophenolate Mofetil Alone and in Combination With Valganciclovir in Renal and Heart Transplant Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00189150
• Other study ID #: Val060
• Status: Completed
• Phase: Phase 4
• First received: September 12, 2005
• Last updated: May 23, 2016
• Start date: April 2005
• Est. completion date: August 2007

Study information

• Verified date: May 2016
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to determine whether a clinically significant PK drug interaction ( a 30% difference in the AUC of MPA) exists between mycophenolate mofetil (under steady state conditions) and VGCV in renal and cardiac transplant recipients.

This study will provide clinically relevant information to the transplant community. It will more clearly delineate whether a clinically significant PK drug interaction exists between mycophenolate mofetil (under steady-state conditions)and VGCV. Given the established dose/efficacy relationship of both MMF and VGCV, this study will provide improved dosing guidelines and potentially avoid adverse outcomes due to empiric dosage adjustments.

Description:

Mycophenolate mofetil (immunosuppressant, MMF) and valganciclovir (antiviral, VGCV) are commonly administered together in transplant patients. Following oral administration, both MMF and VGCV are metabolized to active forms, mycophenolic acid (MPA) and gancoclovir (GCV) respectively. Both MPA and GCV are eliminated through kidney and renal excretion, but there is no data on how MPA pharmacokinetic parameters are affected by GCV at steady state condition. Both MPA and GCV can cause neutropenia and although unsubstantiated, some clinicians have observed an increased occurrence of neutropenia when these agents are used in combination. In the presence of neutropenia, practitioners are often challenged when making decisions regarding whether the dosage of one or both agents should be reduced. It would be useful to know whether the neutropenia is due to increased drug concentration or whether it is due to direct effects of these agents on the bone marrow.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: August 2007
• Est. primary completion date: August 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

The subject must be able to give informed consent for the study. Stable renal or cardiac transplant patients age 18 years and older. Patients must not have had an acute rejection episode within the previous 30 days of the 1st PK study.

Renal transplant patients with serum creatinine < 2 mg/dL and with change in serum creatinine < 25% within the 2 weeks prior to the 1st PK study.

Renal and cardiac transplant patients receiving VGCV for prophylaxis of CMV while concomitantly receiving MMF.

Stable MMF dose: the dose of MMF must not have been adjusted within 1 week of the 1st PK study and must be the same during the 2nd PK study Stable renal function during the study period (change in serum creatinine < 25%)

Exclusion Criteria:

Patients who are not prescribed MMF maintenance therapy or are receiving Myfortic.

Patients who do not require VGCV prophylaxis (CMV negative recipients of CMV negative donor organs).

Patients who have their MMF doses adjusted either < 1 week before the 1st scheduled PK study or anytime during the study period.

Patients whose serum creatinine changes by > 25% within 2 weeks prior to study initiation.

Patients whose hematocrit < 28%. Patients who received other organ transplants in addition to a kidney or heart. Patients who are pregnant or breast-feeding. Patients prescribed bile acids, bile acid sequestrants, potassium binding resins, or magnesium/aluminum-containing antacids.

Study Design

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

Related Conditions & MeSH terms

• Heart Transplant Recipient
• Kidney Transplant Recipient

Intervention

Drug:
• Mycophenolate mofetil

• Valganciclovir

Locations

Country	Name	City	State
United States	University of Michigan Hospital	Ann Arbor	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan	Hoffmann-La Roche

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine whether a clinically significant pharmacokinetic drug interaction exists between mycophenolate mofetil and valganciclovir under steady state conditions in renal and heart transplant recipients
Secondary	To determine whether the effects of valganciclovir on mycophenolate mofetil pharmacokinetic parameters are different between renal and heart transplant recipients