Valganciclovir in Congenital CMV Infants

This study has been completed.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00031434
First received: March 6, 2002
Last updated: February 3, 2011
Last verified: July 2009
  Purpose

The purpose of this study is to evaluate how ganciclovir is metabolized when administered intravenously (by a needle inserted into a vein) following valganciclovir syrup, given by mouth to newborns and young infants with symptoms of congenital (present at birth) cytomegalovirus (CMV) disease. The study also seeks to identify a dose of valganciclovir that provides a comparable blood concentration to ganciclovir present in the blood of newborns with symptomatic congenital CMV disease. All study participants will receive 6 weeks of antiviral therapy (defined as ganciclovir and/or valganciclovir). Infants from 0 to 30 days old will participate in the study for 2 years.


Condition Intervention Phase
Cytomegalovirus Infections
Drug: Valganciclovir
Drug: Ganciclovir
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Pharmacokinetic and Pharmacodynamic Evaluation of Oral Valganciclovir in Neonates With Symptomatic Congenital Cytomegalovirus (CMV) Infection (CASG 109)

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 24
Study Start Date: July 2002
Study Completion Date: July 2007
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
All subjects enrolled into this study will receive 6 weeks (42 days) of antiviral therapy (valganciclovir/ganciclovir).
Drug: Valganciclovir
Valganciclovir is a mono-valyl ester pro-drug of ganciclovir, which is rapidly converted to ganciclovir on absorption. Valganciclovir oral syrup formulation for administration will be provided as a 15g powder blend containing 3g valganciclovir base, for constitution in 120 mL amber glass bottles. The beginning oral valganciclovir dose under investigation is 14 mg/kg. The dose of oral valganciclovir syrup will be adjusted for the baby's weight and renal function. Weights upon which dosage will be adjustments will be made will be obtained on study days 1, 7, 14, 21, 28, and 35.
Drug: Ganciclovir
Ganciclovir for intravenous infusion will be provided as sterile, lyophilized powder in sealed vials containing 500 mg ganciclovir for re-constitution. The dose of intravenous ganciclovir is 6 mg/kg. Intravenous ganciclovir will be adjusted for the baby's weight and renal function. Weights upon which dosage adjustments will be made will be obtained on study days 1, 7, 14, 21, 28, and 35. Each dose of intravenous ganciclovir should be given over 1 hour using an intravenous pump.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 30 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent from parent(s) or legal guardian(s).
  • Culture confirmation of cytomegalovirus (CMV) from urine or throat swab specimens.
  • 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)

  • Less than or equal to 30 days of age at study enrollment.
  • Weight at study enrollment greater than or equal to 1800 grams.
  • Gestational age greater than or equal to 32 weeks.

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 < 10mL/min/1.73 square meters 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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00031434

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, Arkansas
University of Arkansas
Little Rock, Arkansas, United States, 72202-3591
United States, California
University of Southern California
Los Angeles, California, United States, 90033
Children's Hospital of Orange County
Orange, California, United States, 92868
Stanford University
Stanford, California, United States, 94305
United States, Florida
University of Florida
Jacksonville, Florida, United States, 32209
United States, Illinois
Stroger Cook Hospital
Chicago, Illinois, United States, 60612
United States, Kentucky
University of Louisville
Louisville, Kentucky, United States, 40202-3830
United States, Louisiana
Tulane University
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, Missouri
Washington University in St. Louis
Saint Louis, Missouri, United States, 63110
United States, Nebraska
Creighton University
Omaha, Nebraska, United States, 68198-2162
United States, New York
Schneider Children's Hospital
Manhasset, New York, United States, 11030
SUNY Upstate Medical University
Syracuse, New York, United States, 13210
United States, Ohio
MetroHealth Medical Center
Cleveland, Ohio, United States, 44109-1998
Ohio State University
Columbus, Ohio, United States, 43205
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
The University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390-9063
Cook Children's Medical Center
Fort Worth, Texas, United States, 76104
The University of Texas Medical Branch
Galveston, Texas, United States, 77555
The University of Texas Health Science Center
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
  More Information

No publications provided

Responsible Party: Robert Johnson, HHS/NIAID/DMID
ClinicalTrials.gov Identifier: NCT00031434     History of Changes
Other Study ID Numbers: 01-595, CASG 109
Study First Received: March 6, 2002
Last Updated: February 3, 2011
Health Authority: United States: Federal Government
United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Valganciclovir, congenital cytomegalovirus, ganciclovir

Additional relevant MeSH terms:
Cytomegalovirus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Ganciclovir
Valganciclovir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014