Individualization of Ganciclovir and Valganciclovir Doses Using Bayesian Prediction in Renal Transplant Patients.

Nuria Lloberas

Status and phase: Completed; Phase 4

Conditions: Infection in Solid Organ Transplant Recipients

Treatments: Drug: Ganciclovir/ Valganciclovir according to SPC; Drug: Ganciclovir/ Valganciclovir according to PK model

Study type: Interventional

Funder types: Other

Identifiers

NCT01446445

GCV2010

2010-021433-32 (EudraCT Number)

Details and patient eligibility

About

The objective of the present study is to optimize intravenous ganciclovir(GCV) and oral valganciclovir (VGCV)doses, advised by the drug exposure, indicated by the area under the concentration time curve (AUC), in renal transplant patients receiving oral VGCV or intravenous GCV for CMV prophylaxis or treatment. The initial doses will be calculated according to population pharmacokinetic model. Subsequent doses will be adjusted according to plasma GCV concentrations, using the Bayesian approach. This method of dose adjustments could lead to increase the percentage of patients achieving a therapeutic exposure.

Full description

The area under the concentration time curve of serum concentrations of GCV is an indicator of systemic exposure to the drug and is related to the effectiveness and safety. According to the population model developed by our group, less than 16% of patients treated achieve the therapeutic goal of AUC (40 to 50 mcg • h / L) after drug dosing according to summary of product characteristics (SPC). Especially, patients with impaired renal function values (creatinine clearance (CrC)l <30 ml / min) or high (CrCl> 70 ml / min) would be overdosed and underdosed, respectively, with the risk of more adverse effects or therapeutic failure.

Therefore, the individualization of the dosage of GCV, can contribute greatly to achieve optimal exposure to the drug in transplant patients, especially in the cases of extreme values of renal function (CrCl decreased and high). As a consequence, minimize adverse effects, ensure greater efficiency in the target population and reduce associated costs.

Enrollment: 60 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subjects must be 18 or older, weigh more than 34kg and may be of either sex and race.
• Subjects must be willing to give informed consent (IC) in writing and be able to do and follow the study. If a subject cannot give informed consent in writing , a legal representative could sign in his place.
• Women of childbearing potential should perform a pregnancy test at the time of entry and accept the use of a medically acceptable contraceptive method during the study.

Exclusion criteria

• Creatinine Clearance (CrCl )<10 mL / min.
• Subjects may not have a history of type I hypersensitivity or idiosyncratic reactions to drugs ganciclovir/valganciclovir
• Pregnancy women.
• Women breast feeding
• Subjects may not present at time of inclusion any clinically significant disease that could interfere with study evaluations.
• Previous participation in another clinical trial sponsored by pharmaceutical industry, in which the promoter and the protocol set which should be the treatment for CMV.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 4 patient groups

1.A (Prophylaxis-SPC)

Active Comparator group

Description:

Prophylaxis for CMV infection and Ganciclovir/ Valganciclovir doses according to summaries of product characteristics (SPC).

Treatment:

Drug: Ganciclovir/ Valganciclovir according to SPC

1.B (Prophylaxis- PK model)

Experimental group

Description:

Prophylaxis for CMV infection and Ganciclovir/Valganciclovir doses according to pharmacokinetic model.

Treatment:

Drug: Ganciclovir/ Valganciclovir according to PK model

2.A (Treatment-SPC)

Active Comparator group

Description:

Treatment for CMV infection/disease and Ganciclovir/ Valganciclovir doses according to summaries of product characteristics (SPC).

Treatment:

Drug: Ganciclovir/ Valganciclovir according to SPC

2.B (Treatment-PK model)

Experimental group

Description:

Treatment for CMV infection/disease and Ganciclovir/Valganciclovir doses according to pharmacokinetic model

Treatment:

Drug: Ganciclovir/ Valganciclovir according to PK model