Valganciclovir in Congenital CMV Infants

• Pharmacokinetics of ganciclovir following administration of oral valganciclovir syrup. The pharmacokinetics will be assessed by a population approach to PK data analysis. [ Time Frame: Day 1: 0.25-0.75, 1-3, 5-7, and 10-12 hours. Day 3: with 2nd dose of IV ganciclovir, before dose, 1 hour, 2-3, 5-7, and 10-12 hours after dose. 1 and 2 weeks post oral valganciclovir: 0.5 after the am dose and 3 hours after the 1st PK. ] [ Designated as safety issue: No ]
  

• Pharmacokinetics of valganciclovir following administration of oral valganciclovir syrup. [ Time Frame: Day 1: 0.25-0.75, 1-3, 5-7, and 10-12 hours. 1 and 2 weeks post oral valganciclovir: 0.5 after the am dose and 3 hours after the 1st PK. ] [ Designated as safety issue: No ]
  
• Lack of vomiting and/or diarrhea associated with administration of oral valganciclovir syrup. [ Time Frame: Assessed through Day 56. ] [ Designated as safety issue: No ]
  
• Correlation of ganciclovir plasma concentrations following administration of intravenous ganciclovir and oral valganciclovir syrup with CMV whole blood viral load. [ Time Frame: Day 1 (prior to dose 1 of valganciclovir), Day 7, Day 14, Day 28, Day 42, Day 56, and 6 months. ] [ Designated as safety issue: No ]
  
• Assessment of toxicity, such as neutropenia, associated with the administration of oral valganciclovir syrup. [ Time Frame: Duration of study. ] [ Designated as safety issue: Yes ]
  

Recent trials have demonstrated that ganciclovir treatment of neonates with symptomatic congenital cytomegalovirus (CMV) disease involving the central nervous system results in improved hearing function (or maintenance of normal hearing function) and prevents hearing deterioration at 6 months. Furthermore, ganciclovir therapy may prevent hearing deterioration at 1 year. Ganciclovir recipients also have a more rapid resolution of their transaminase elevations and a greater degree of short term growth in weight and head circumference compared with untreated patients. Valganciclovir, the oral product of ganciclovir, has been developed as a syrup formulation and presents the opportunity to treat longer, but pharmacokinetic data are needed in infants first to assure the correct dose is being utilized. This Phase I/II, multi-center, open-label trial will assess the safety/tolerability and pharmacokinetics (ganciclovir concentrations) following administration of oral valganciclovir to neonates with symptomatic congenital CMV disease. A total of 24 patients will be evaluated. All patients entered into this study will receive 6 weeks (42 days) of antiviral therapy (defined as ganciclovir and/or valganciclovir). Two different dose determination strategies will be applied in this protocol. The first is an individual patient approach. The second is a group dose modification strategy. The primary endpoint is pharmacokinetics of ganciclovir following administration of oral valganciclovir syrup. The pharmacokinetics will be assessed by a population approach to PK data analysis. Secondary endpoints are: the pharmacokinetics of valganciclovir following administration of oral valganciclovir; the correlation of ganciclovir plasma concentrations following administration of intravenous ganciclovir and oral valganciclovir syrup with CMV whole blood viral load; lack of vomiting and/or diarrhea associated with the administration of oral valganciclovir syrup; and assessment of toxicity, such as neutropenia, associated with the administration of oral valganciclovir syrup.