Pharmacokinetic Study Of Valaciclovir Hydrochloride Tablets

Condition(s) targeted: Renal Impairment

Intervention: Valaciclovir Hydrochloride (Drug)

Phase: Phase 4

Status: Terminated

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, MD, Study Director, Affiliation: GlaxoSmithKline

Valaciclovir (VACV), the L-valyl ester prodrug of aciclovir (ACV), is extensively converted to ACV and L-valine after oral administration. In subjects with normal renal function, ACV is predominantly eliminated unchanged in the urine, with a small proportion metabolized to 9-carboxymethoxymethylguanine (CMMG). The metabolism of ACV to CMMG is thought to involve aldehyde dehydrogenase (ALDH). On the basis of a high proportion of the Japanese population having low-activity ALDH, it can be hypothesized that the conversion of ACV to CMMG is decreased, thereby leading, in patients with renal impairment, to higher plasma concentrations of ACV. This pilot study was conducted to investigate potential relationships between genetic polymorphisms of ALDH2, an isozyme of ALDH, and the plasma pharmacokinetics (PK) of VACV, ACV and CMMG in subjects with end-stage renal disease on hemodialysis.

Official title: Post-Marketing Clinical Study of Valaciclovir Hydrochloride Tablets -Single Oral Dose Study in Hemodialysis Patients-

Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics Study

Primary outcome: - The pharmacokinetic parameters for VACV, ACV and CMMG - Relationship between ALDH2 genotypes and the pharmacokinetics of VACV, ACV and CMMG in blood

Secondary outcome: - Change in blood ACV and CMMG concentrations after a 4-hour hemodialysis session - Safety (adverse events occurring during the study, clinical laboratory tests)

Minimum age: 20 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion criteria:

- Japanese subjects with chronic renal failure undergoing hemodialysis regularly three

times a week for at least 12 weeks prior to the start of the study.

Exclusion criteria:

- Subjects with current alcohol dependence.

- Subjects with gastrointestinal dysfunction that may affect drug absorption.

- Subjects who have received an organ transplant (However, subjects with a corneal

transplant or any other organ transplant that may not affect the objectives of the study will be eligible for inclusion in this study).

GSK clinical trials call center, Shizuoka 431, Japan

GSK clinical trials call center, Shizuoka 432, Japan

Starting date: July 2005
Last updated: June 21, 2006