A Relative Bioavailability Study of Valcyte (Valganciclovir) in Lung Transplant Recipients With or Without Cystic Fibrosis.

Study Overview
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Brief Summary
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This study will assess the relative bioavailability of ganciclovir from the pro-drug valganciclovir in lung transplant recipients with or without cystic fibrosis. Each patient will receive 900mg valganciclovir daily for the period specified at their center, starting as soon as possible after the transplant. Pharmacokinetic assessments will be made provided that steady-state kinetics of ganciclovir and immunosuppressive drugs have been obtained (>=4 days of drug therapy). Blood samples for pharmacokinetic analysis will be taken up to 24h post-dose on one occasion. The anticipated time on study treatment is 3-12 months, and the target sample size is <100 individuals.

Official Title
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Relative Bioavailability Study of Ganciclovir From the Pro-drug, Valganciclovir, in Lung Transplant Recipients With or Without Cystic Fibrosis

Conditions
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Cytomegalovirus Infections

Intervention / Treatment
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* Drug: valganciclovir [Valcyte]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male or female patients, >=14 years of age; first lung or heart-lung transplant recipient; at risk of CMV disease (D+R-,D+R+ or D-R+); estimated creatinine clearance >=60mL/min; stable immunosuppressive and 900mg Valcyte dosing regimens (>=4 days) prior to pharmacokinetic assessments. Exclusion Criteria: history of any adverse reaction to acyclovir, valacyclovir, ganciclovir or valganciclovir; evidence of graft rejection; patient has received anti-CMV prophylaxis with a treatment other than cytogam, ganciclovir or valganciclovir between transplant and screening.

Ages Eligible for Study
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Minimum Age: 14 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: valganciclovir [Valcyte]<br>* 900mg po<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under The Observed Plasma Concentration-Time Curve Between Dosing Intervals AUC(0-tau) | The area under the plasma concentration-time curve from time zero to end of dosing interval (AUC [0-tau]) is a measure of the plasma ganciclovir concentration from time zero to end of dosing interval. It was computed using the linear trapezoidal rule. The pharmacokinetic parameters of valganciclovir were measured in plasma of all participants following a single oral dose valganciclovir at 900 mg on Day 1. | Pre-dose, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12 and 24 hours post-dose | 
| Maximum Observed Plasma Concentration (Cmax) of Ganciclovir | The Cmax is defined as maximum observed Ganciclovir concentration. Cmax of valganciclovir were measured in plasma of all participants following a single tablet dose Valganciclovir at 900 mg at start of treatment on Day 1. | Pre-dose, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12 and 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Maximum Observed Plasma Concentration (Tmax) of Ganciclovir | The Tmax is defined as time to reach maximum observed Ganciclovir concentration. The pharmacokinetic parameters of Valganciclovir were measured in plasma of all participants following a single tablet dose Valganciclovir at 900 mg at start of treatment on Day 1. | Pre-dose, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12 and 24 hours post-dose | 
| Apparent Elimination Rate (Kelim) of Ganciclovir | The apparent elimination rate is equal to the magnitude of the slope from the log-linear regression of plasma concentration versus time over the interval t to 24, where t is the first time-point used for this regression. Kelim was not reported for those participants for whom R-squared (adjusted) was lower than 0.70. | Pre-dose, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12 and 24 hours post-dose | 
| Plasma Half-Life (T1/2) of Ganciclovir | Plasma half-life is the time measured for the plasma concentration to decrease by one half. The pharmacokinetic parameters of Valganciclovir were measured in plasma of all participants following a single tablet dose Valganciclovir at 900 mg at start of treatment on Day 1. T1/2 was not reported for those participants for whom R-squared (adjusted) was lower than 0.70. | Pre-dose, 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12 and 24 hours post-dose |