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

Phase 1

Completed

Brief Summary: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
1	valganciclovir [Valcyte]	-

Primary Outcome Measures

Name	Time	Method
Area Under The Observed Plasma Concentration-Time Curve Between Dosing Intervals AUC(0-tau)	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	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.
Maximum Observed Plasma Concentration (Cmax) of Ganciclovir	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	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.

Secondary Outcome Measures

Name	Time	Method
Plasma Half-Life (T1/2) of Ganciclovir	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 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.
Time to Maximum Observed Plasma Concentration (Tmax) of Ganciclovir	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	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.
Apparent Elimination Rate (Kelim) of Ganciclovir	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	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.