Primary:

o To determine the pharmacokinetics of ganciclovir following administration of oral valganciclovir syrup in neonates and young infants with symptomatic congenital CMV disease

o To identify a dose of valganciclovir to provide comparable ganciclovir plasma concentrations in neonates and young infants with symptomatic congenital CMV disease.

Secondary:

o To evaluate the safety and tolerability of valganciclovir syrup in the neonatal and infantile populations

o To determine the pharmacodynamics of ganciclovir following administration of oral valganciclovir syrup in neonates and young infants with symptomatic congenital CMV disease.

Condition	Treatment or Intervention	Phase
Cytomegalovirus Infections	Drug: Ganciclovir  Drug: Valganciclovir (Oral)	Phase I Phase II

Further Study Details: 

Expected Total Enrollment:  24

Recent trials have demonstrated that ganciclovir treatment of neonates with symptomatic congenital CMV disease involving the CNS 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.

Ganciclovir therapy must be administered intravenously and often requires the establishment of a central line in these babies. Valganciclovir, the oral prodrug of ganciclovir, has been developed as a syrup formulation and presents the opportunity to treat longer without the requirement for a central line, 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.

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 intravenous ganciclovir or oral valganciclovir syrup with CMV whole blood viral load; the incidence of emesis following oral valganciclovir administration (tolerability); safety as assessed by neutropenia incidence

Ages Eligible for Study:  up to  1 Month,  Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:

• Signed informed consent from parent(s) or legal guardian(s).
• Culture confirmation of cytomegalovirus from urine or throat swab specimens.
• Less than or equal to 30 days of age at study enrollment.
• Weight at study enrollment > or equal to 1800 grams
• Gestational age greater than or equal to 32 weeks.

Symptomatic congenital CMV disease, as manifest by one or more of the following:

• Thrombocytopenia
• Petechiae
• Hepatomegaly
• Splenomegaly
• Intrauterine growth restriction
• Hepatitis (elevated transaminases and/or bilirubin
• Central nervous system involvement of the CMV disease (such as microcephaly, radiographic abnormalities indicative of CMV CNS disease, abnormal CSF indices for age, chorioretinitis, hearing deficits as detected by brainstem evoked response, and/or positive CMV PCR from CSF)

EXCLUSION CRITERIA:

• Imminent demise.
• Patients receiving other antiviral agents or immune globulin.
• Gastrointestinal abnormality which might preclude absorption of an oral medication (e.g., a history of necrotizing enterocolitis).
• Creatinine clearance less than 10 mL/min at time of study enrollment.
• Infants known to be born to women who are HIV positive (but HIV testing is not required for study entry).

Penny Jester      877-975-7280    pjester@peds.uab.edu

Alabama
      University of Alabama at Birmingham (CASG), Birmingham,  Alabama,  35294,  United States; Recruiting
Arkansas
      Arkansas Children's Hospital, Little Rock,  Arkansas,  72202,  United States; Recruiting
California
      Stanford University, Stanford,  California,  94305-52,  United States; Recruiting
      Children's Hospital of Orange County, Orange,  California,  92868,  United States; Recruiting
Florida
      University of Florida HSC - Jacksonville, Jacksonville,  Florida,  32209,  United States; Recruiting
Kansas
      University of Kansas, Kansas City,  Kansas,  66160,  United States; Recruiting
      Via Christi Regional Medical Center, Wichita,  Kansas,  67214,  United States; Recruiting
Kentucky
      University of Louisville Health Sciences Center, Louisville,  Kentucky,  40292,  United States; Recruiting
Louisiana
      Tulane University Health Sciences Center, New Orleans,  Louisiana,  70112,  United States; Recruiting
Maryland
      Johns Hopkins University, Baltimore,  Maryland,  21287-25,  United States; Recruiting
Missouri
      St. Louis University, St. Louis,  Missouri,  63104,  United States; Recruiting
      Washington University, St. Louis,  Missouri,  63110,  United States; Recruiting
Nebraska
      Creighton University, Omaha,  Nebraska,  68178,  United States; Recruiting
New York
      State University New York Stony Brook, Stony Brook,  New York,  11794,  United States; Recruiting
      SUNY Upstate Medical University, Syracuse,  New York,  13210,  United States; Recruiting
      North Shore - Long Island Jewish Health System, Manhasset,  New York,  11030,  United States; Recruiting
Ohio
      MetroHealth Medical Center of Cleveland, Cleveland,  Ohio,  44109,  United States; Recruiting
Pennsylvania
      Thomas Jefferson University, Philadelphia,  Pennsylvania,  19107,  United States; Recruiting
Texas
      University of Texas Hlth Sci Ctr San Ant, San Antonio,  Texas,  78284-78,  United States; Recruiting
      Cook - Fort Worth Children's Medical Center, Fort Worth,  Texas,  76104,  United States; Recruiting
      University of Texas Southwestern Medical Center, Dallas,  Texas,  75235,  United States; Recruiting
Canada, Alberta
      University of Alberta, Edmonton,  Alberta,  T6G2B7,  Canada; Recruiting
Canada, Manitoba
      University of Manitoba - Winnipeg, Winnipeg,  Manitoba,  R3T 2N2,  Canada; Recruiting

Study ID Numbers:  01-595
Record last reviewed:  November 2004
Last Updated:  December 29, 2004
Record first received:  March 6, 2002
ClinicalTrials.gov Identifier:  NCT00031434
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08