John S Bradley1, Jeffrey L Blumer2, José R Romero3, Marian G Michaels4, Flor M Munoz5, David W Kimberlin6, Barbara Pahud7, Roberta L DeBiasi8, Go Yamamoto9, Grace Roberts10, Mohammad Hossain11, Denise Shortino12, Phillip J Yates13, Bryan Adams11, Amanda Peppercorn14. 1. Division of Infectious Diseases, Department of Pediatrics, University of California San Diego and Rady Children's Hospital, San Diego, California; jbradley@rchsd.org. 2. Department of Pediatrics, University of Toledo, Toledo, Ohio. 3. Division of Infectious Diseases, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas. 4. Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania. 5. Departments of Pediatrics and Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas. 6. Division of Pediatric Infectious Diseases, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama. 7. Department of Pediatrics, Children's Mercy Hospital and University of Missouri-Kansas City, Kansas City, Missouri. 8. Children's National Medical Center and Department of Pediatrics, The George Washington University School of Medicine, Washington, District of Columbia. 9. Yamamoto Pediatric Clinic, Fukuoka, Japan. 10. GlaxoSmithKline, Research Triangle Park, North Carolina. 11. GlaxoSmithKline, Upper Merion, Pennsylvania. 12. PAREXEL International, Durham, North Carolina. 13. GlaxoSmithKline, Stevenage, Hertfordshire, United Kingdom; and. 14. GlaxoSmithKline, Boston, Massachusetts.
Abstract
BACKGROUND: Children with severe influenza infection may require parenteral therapy if oral or inhaled therapies are ineffective or cannot be administered. Results from a study investigating intravenous (IV) zanamivir for the treatment of hospitalized infants and children with influenza are presented. METHODS: This phase II, open-label, multicenter, single-arm study assessed the safety of investigational IV zanamivir in hospitalized children with influenza. Safety outcomes included treatment-emergent adverse events (TEAEs), clinical laboratory measurements, and vital signs. Clinical outcomes, pharmacokinetics, and virologic efficacy data were collected as key secondary outcomes. RESULTS: In total, 71 children received treatment with investigational IV zanamivir (exposure comparable to 600 mg twice daily in adults). TEAEs and serious TEAEs (STEAEs) were reported in 51 (72%) and 15 (21%) patients, respectively. The mortality rate was 7%, and median durations of hospital and ICU stays were 6 and 7.5 days, respectively. No STEAEs or deaths were considered related to IV zanamivir treatment, and no patterns of TEAEs, laboratory abnormalities, or vital signs were observed. The mean zanamivir exposures from 34 patients with normal renal function who received 12 mg/kg, 14 mg/kg, or 600 mg of IV zanamivir ranged from 64.5 to 110 hour·µg/mL. The median change from baseline in the viral load was -1.81 log10 copies per mL after 2 days of treatment. CONCLUSIONS: The safety profile of IV zanamivir was favorable, with no drug-related STEAEs reported. The majority of children experienced virologic response and clinical improvement during the treatment course. Systemic zanamivir exposures in children were consistent with adults.
BACKGROUND:Children with severe influenza infection may require parenteral therapy if oral or inhaled therapies are ineffective or cannot be administered. Results from a study investigating intravenous (IV) zanamivir for the treatment of hospitalized infants and children with influenza are presented. METHODS: This phase II, open-label, multicenter, single-arm study assessed the safety of investigational IV zanamivir in hospitalized children with influenza. Safety outcomes included treatment-emergent adverse events (TEAEs), clinical laboratory measurements, and vital signs. Clinical outcomes, pharmacokinetics, and virologic efficacy data were collected as key secondary outcomes. RESULTS: In total, 71 children received treatment with investigational IV zanamivir (exposure comparable to 600 mg twice daily in adults). TEAEs and serious TEAEs (STEAEs) were reported in 51 (72%) and 15 (21%) patients, respectively. The mortality rate was 7%, and median durations of hospital and ICU stays were 6 and 7.5 days, respectively. No STEAEs or deaths were considered related to IV zanamivir treatment, and no patterns of TEAEs, laboratory abnormalities, or vital signs were observed. The mean zanamivir exposures from 34 patients with normal renal function who received 12 mg/kg, 14 mg/kg, or 600 mg of IV zanamivir ranged from 64.5 to 110 hour·µg/mL. The median change from baseline in the viral load was -1.81 log10 copies per mL after 2 days of treatment. CONCLUSIONS: The safety profile of IV zanamivir was favorable, with no drug-related STEAEs reported. The majority of children experienced virologic response and clinical improvement during the treatment course. Systemic zanamivir exposures in children were consistent with adults.
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