Valganciclovir in Congenital CMV Infants

NCT00031434 | Completed Phase 1

• 2 other identifiers: 01-595CASG 109
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 21

Brief Summary

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.

Conditions

Cytomegalovirus Infections

Keywords

Valganciclovir, congenital cytomegalovirus, ganciclovir

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetics of ganciclovir following administration of oral valganciclovir syrup. The pharmacokinetics will be assessed by a population approach to PK data analysis.

  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.

Secondary Outcomes (4)

• Pharmacokinetics of valganciclovir following administration of oral valganciclovir syrup.

  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.

• Lack of vomiting and/or diarrhea associated with administration of oral valganciclovir syrup.

  Assessed through Day 56.

• Correlation of ganciclovir plasma concentrations following administration of intravenous ganciclovir and oral valganciclovir syrup with CMV whole blood viral load.

  Day 1 (prior to dose 1 of valganciclovir), Day 7, Day 14, Day 28, Day 42, Day 56, and 6 months.

• Assessment of toxicity, such as neutropenia, associated with the administration of oral valganciclovir syrup.

  Duration of study.

Study Arms (1)

1

EXPERIMENTAL

All subjects enrolled into this study will receive 6 weeks (42 days) of antiviral therapy (valganciclovir/ganciclovir).

Drug: Valganciclovir; Drug: Ganciclovir

Interventions

Valganciclovir DRUG

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.

1

Ganciclovir DRUG

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.

1

Eligibility Criteria

• Age: Up to 30 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (21)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of Arkansas

Little Rock, Arkansas, 72202-3591, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

University of Florida

Jacksonville, Florida, 32209, United States

Location

Stroger Cook Hospital

Chicago, Illinois, 60612, United States

Location

University of Louisville

Louisville, Kentucky, 40202-3830, United States

Location

Tulane University

New Orleans, Louisiana, 70112, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Creighton University

Omaha, Nebraska, 68198-2162, United States

Location

Schneider Children's Hospital

Manhasset, New York, 11030, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, 44109-1998, United States

Location

Ohio State University

Columbus, Ohio, 43205, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

The University of Texas Southwestern Medical Center

Dallas, Texas, 75390-9063, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

The University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

The University of Texas Health Science Center

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Cytomegalovirus Infections; Multiple Acyl Coenzyme A Dehydrogenase Deficiency

Interventions

Valganciclovir; Ganciclovir

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Mitochondrial Diseases

Intervention Hierarchy (Ancestors)

Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 6, 2002
• First Posted: March 7, 2002
• Study Start: July 1, 2002
• Primary Completion: July 1, 2007
• Study Completion: July 1, 2007
• Last Updated: February 7, 2011

Record last verified: 2009-07

Locations

US (21)