Clinical trial NCT00189150: Pharmacokinetics of Mmf and Valganciclovir
Official title: Pharmacokinetics of Mycophenolate Mofetil Alone and in Combination With Valganciclovir in Renal and Heart Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Kidney Transplant Recipient
Heart Transplant Recipient
Keywords: Valganciclovir
Mycophenolate Mofetil
Pharmacokinetic
Interaction
MPA
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2005-09-16
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

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Primary outcomes:
measure: 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 outcomes:
measure: To determine whether the effects of valganciclovir on mycophenolate mofetil pharmacokinetic parameters are different between renal and heart transplant recipients
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Hospital
state: Michigan
Study officials:
affiliation: University of Michigan Hospital
name: Jeong M Park, MS, PharmD
role: PRINCIPAL_INVESTIGATOR
References: