Herpes zoster is a common infectious disease that can result in significant acute and chronic morbidity. The safety and efficacy of once-daily oral valomaciclovir (EPB-348) was evaluated for non-inferiority to 3-times daily valacyclovir, an approved therapy. In this study, 373 immunocompetent adults with onset of a herpes zoster rash within the preceding 72 hr were randomly assigned to receive one of four treatments for 7 days: (1) EPB-348 1,000 mg once-daily; (2) EPB-348 2,000 mg once-daily; (3) EPB-348 3,000 mg once-daily; or (4) valacyclovir 1,000 mg 3-times daily. A 20% margin was the reference for non-inferiority assessment. For the primary efficacy measure of time to complete crusting of the zoster rash by Day 28, non-inferiority criteria were met for once-daily EPB-348 2,000 mg and once-daily EPB-348 3,000 mg compared to 3-times daily valacyclovir. Additionally, EPB-348 3,000 mg significantly shortened the time to complete rash crusting by Day 28 compared to valacyclovir. For secondary efficacy measures, non-inferiority was achieved for the EPB-348 1,000 and 2,000 mg groups compared to the valacyclovir group for time to rash resolution by Day 28. No EPB-348 group was non-inferior to valacyclovir for time to cessation of new lesion formation or time to cessation of pain by Day 120, though no significant differences occurred between treatment groups. Nausea, headache, and vomiting were the most common adverse events. Based on these results, additional studies are warranted to define further EPB-348's potential as an effective and safe therapy for acute herpes zoster.
BackgroundPeramivir (PVR) is a potent neuraminidase inhibitor with in vitro activity against all influenza virus subtypes. Previous studies demonstrated the efficacy and safety of PVR as a single dose intravenous (IV) treatment for acute uncomplicated influenza in adults.MethodsA phase 3 study compared age-appropriate doses of single dose IV PVR to 5 days of oral oseltamivir (OSE) (4:1 randomization, stratified by age) in pediatric subjects age 0 -17 years within 48 hours of onset of acute uncomplicated influenza. Plasma concentrations of PVR were measured up to 6 hours post dose. Serial viral titers were measured from nasopharyngeal swabs. Severity of influenza signs and symptoms were recorded in a diary.Results122 subjects were enrolled up to a data cutoff of March 31, 2017 (<2 yrs, n = 7; 2-<7yrs, n = 37; 7-<13 yrs, n = 48; 13–17 yrs, n = 30). Interim results are reported for the first 108 subjects randomized, of which 101 (94%) received study drug. Influenza was confirmed by PCR in 75 (74%) subjects who received study drug (Intent-to-treat-Infected [ITTI] population). Key endpoints are summarized:PVROSEIntent to treat (ITT) population: n (all age groups)8523ITTI population: n (%)5916A/H1N122 (37%)9 (56%)A/H3N212 (20%)3 (19%)A/Ind1 (2%)0 (0%)B23 (39%)4 (25%)A + B1 (2%)0 (0%)Proportion of ITTI population shedding virus1, n (%)Baseline53/59 (90%)14/16 (88%)Day 327/59 (46%)10/16 (63%)Day 72/59 (3%)0/16 (0%)Day 140/59 (0%)0/16 (0%)Time to alleviation of symptoms, hrs275.6 (47.0, 109.2)99.8 (34.7, 133.6)Time to resolution of fever, hrs240.5 (22.1, 47.0)34.7 (13.7, 42.3) 1Determined by virus culture assay; 2ITTI population: median (95% CI).No serious adverse events were reported. AEs occurring in more than two subjects overall were:PVROSESafety population: n7823Any event17 (22%)5 (22%)Vomiting2 (3%)2 (9%)Nausea0 (0%)2 (9%)Pyrexia2 (3%)0 (0%)Tympanic membrane hyperemia2 (3%)0 (0%)ConclusionTreatment of influenza in pediatric subjects with single dose IV PVR or 5 days of oral OSE was generally safe and well tolerated. Whilst not powered for efficacy differences, trends were observed in more rapid reduction in virus shedding and symptom alleviation for PVR treated subjects compared with OSE. The study continues to enroll subjects < 7 years.Disclosures J. Vanchiere, BioCryst Pharmaceuticals: Consultant and Investigator, Consulting fee and Research support; S. Plunkett, BioCryst Pharmaceuticals: Investigator, Research support; R. Annamalai, BioCryst Pharmaceuticals: Investigator, Research support; K. Julien, BioCryst Pharmaceuticals: Investigator, Research support; J. Peterson, BioCryst Pharmaceuticals: Investigator, Research support; M. Goisse, BioCryst Pharmaceuticals: Investigator, Research support; S. Christensen, BioCryst Pharmaceuticals: Investigator, Research support; P. Mehta, BioCryst Pharmaceuticals: Investigator, Research support; S. Coleman, BioCryst Pharmaceuticals: Investigator, Research support; F. Munoz, BioCryst Pharmaceuticals: Investigator, Research support; A. Flynt, BioCryst Pharmaceuticals: ...
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