Pharmacokinetics of Oseltamivir in Newborns and Infants

Prematurity of Fetus Clinical Trial

Official title:

Pharmacokinetics of Oseltamivir in Newborns and Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01388439
• Other study ID #: TAM 027
• Status: Completed
• Phase: N/A
• First received: June 24, 2011
• Last updated: July 5, 2011
• Start date: January 2011
• Est. completion date: January 2011

Study information

• Verified date: June 2011
• Source: St. Louis Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

Oseltamivir dosing in infants < 3 months of age is based on a single pharmacokinetic study in 20 infants from a single center. This dataset is limited by a lack of robustness, because only 1 sample was collected from each participant. The investigators obtained two blood samples each from infants receiving oseltamivir after obtaining informed consent from the infant's parents. The investigators propose to analyze the blood samples to determine the amount of oseltamivir in the infant's blood. Measurement of these values will increase the understanding of the absorption and elimination of oseltamivir in preterm and term infants, and improve our ability to provide the correct doses to this high risk population.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 6 Months

Eligibility

Inclusion Criteria:

• All neonates and infants in the NICU at St. Louis Children's Hospital who received oseltamivir for treatment of or exposure to influenza virus type A were considered eligible for this study.

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Prematurity of Fetus

Intervention

Drug:
• Oseltamivir
Treatment dose was oseltamivir 3 mg/kg/dose by mouth (PO) twice daily. Prophylactic dose was oseltamivir 1 mg/kg/dose PO once daily to infants < 28 weeks postmenstrual age (PMA), 1 mg/kg/dose PO twice daily to infants 28 - 38 weeks PMA, and 3 mg/kg/dose PO once daily to infants > 38 weeks PMA. Dosing in infants < 28 weeks PMA was chosen based on unpublished data from Acosta et al. This data was obtained from phone contact with Dr. Peter Gal, co-author of the study. Dosing in infants 28 - 38 weeks PMA was chosen based on published data from Acosta et al.1 Dosing in infants > 38 weeks PMA and less than 3 months postnatal age was chosen based on data from Kimberlin et al. Dosing in infants > 38 weeks PMA and greater than 3 months postnatal age was per the recommendations of the Advisory Committee on Immunization Practices of the United States Department of Health and Human Services.

Locations

Country	Name	City	State
United States	St. Louis Children's Hosptial	St. Louis	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
St. Louis Children's Hospital	Genentech, Inc., Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (2)

Acosta EP, Jester P, Gal P, Wimmer J, Wade J, Whitley RJ, Kimberlin DW; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Oseltamivir dosing for influenza infection in premature neonates. J Infect Dis. 2010 Aug 15;202(4):563-6. doi: 10.1086/654930. — View Citation

Fiore AE, Fry A, Shay D, Gubareva L, Bresee JS, Uyeki TM; Centers for Disease Control and Prevention (CDC). Antiviral agents for the treatment and chemoprophylaxis of influenza --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011 Jan 21;60(1):1-24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Oseltamivir pharmacokinetics in neonates and infants	Pharmacokinetic parameters calculated for individual subjects will include apparent distribution volume and elimination half-life of oseltamivir (OST) and OST carboxylate (CBX). Area under the plasma concentration versus time curve (AUC) of OST and OST CBX will be determined using the trapezoidal method. A population pharmacokinetic model will be generated based on pooled pharmacokinetic data (2-compartment model for OST and 1-compartment model for OST CBX) utilizing maximum likelihood estimation. A weight-based dosing table will be generated to provide AUC exposures comparable to adults.	Two sample points, one 0-3 hours (baseline) and one 3-24 hours post dose	No
Secondary	Oseltamivir target level attainment	OST target level attainment of the currently recommended dosing regimen in neonates and infants will be calculated. Currently recommended doses were utilized for all neonates and infants in our cohort. The target level attainment in this cohort will be calculated.	Two sample points, one 0-3 hours (baseline) and one 3-24 hours post dose	No