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

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

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.

Study Overview

• Status: Completed
• Conditions: Cytomegalovirus Infections
• Intervention / Treatment: Drug: valganciclovir [Valcyte]

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
  • Colorado
    • Denver, Colorado, United States, 80262
  • North Carolina
    • Durham, North Carolina, United States, 27710
  • Ohio
    • Cleveland, Ohio, United States, 44195
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: valganciclovir [Valcyte]; 900mg po

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (Actual): June 1, 2006
• Study Completion (Actual): June 1, 2006

Study Registration Dates

• First Submitted: September 15, 2006
• First Submitted That Met QC Criteria: September 15, 2006
• First Posted (Estimate): September 18, 2006

Study Record Updates

• Last Update Posted (Estimate): December 31, 2015
• Last Update Submitted That Met QC Criteria: November 26, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; DNA Virus Infections; Herpesviridae Infections; Pancreatic Diseases; Cystic Fibrosis; Cytomegalovirus Infections; Anti-Infective Agents; Antiviral Agents; Valganciclovir
• Other Study ID Numbers: WP18046