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

• ClinicalTrials.gov Identifier: NCT00377741
• Recruitment Status: Completed
• First Posted: September 18, 2006
• Results First Posted: December 31, 2015
• Last Update Posted: December 31, 2015
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cytomegalovirus Infections	Drug: valganciclovir [Valcyte]	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Relative Bioavailability Study of Ganciclovir From the Pro-drug, Valganciclovir, in Lung Transplant Recipients With or Without Cystic Fibrosis
• Study Start Date: December 2004
• Actual Primary Completion Date: June 2006
• Actual Study Completion Date: June 2006

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1	Drug: valganciclovir [Valcyte]; 900mg po

Outcome Measures

Primary Outcome Measures :

1. Area Under The Observed Plasma Concentration-Time Curve Between Dosing Intervals AUC(0-tau) [ Time Frame: 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.
2. Maximum Observed Plasma Concentration (Cmax) of Ganciclovir [ Time Frame: 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 :

1. Time to Maximum Observed Plasma Concentration (Tmax) of Ganciclovir [ Time Frame: 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.
2. Apparent Elimination Rate (Kelim) of Ganciclovir [ Time Frame: 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.
3. Plasma Half-Life (T1/2) of Ganciclovir [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, California

Los Angeles, California, United States, 90033

United States, Colorado

Denver, Colorado, United States, 80262

United States, North Carolina

Durham, North Carolina, United States, 27710

United States, Ohio

Cleveland, Ohio, United States, 44195

United States, Pennsylvania

Pittsburgh, Pennsylvania, United States, 15213

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00377741
• Other Study ID Numbers: WP18046
• First Posted: September 18, 2006
• Results First Posted: December 31, 2015
• Last Update Posted: December 31, 2015
• Last Verified: November 2015

Additional relevant MeSH terms:

Cytomegalovirus Infections; Cystic Fibrosis; Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Valganciclovir; Antiviral Agents; Anti-Infective Agents