A Phase 2 Study of Pimodivir (JNJ-63623872) in Combination With Oseltamivir in Elderly and Nonelderly Adults Hospitalized With Influenza A Infection: OPAL Study
Brian J. O’Neil, Michael G. Ison, Marie Charlotte Hallouin-Bernard, Anna Nilsson, Antoní Torres, John Wilburn, Wilbert van Duijnhoven, Ilse Van Dromme, David Anderson, Sofie Deleu, Teddy Kosoglou, Johan Vingerhoets, Stefaan Rossenu, Lorant Leopold
Abstract
BACKGROUND: Both the elderly and individuals with comorbidities are at increased risk of developing influenza-related complications. Novel influenza antivirals are required, given limitations of current drugs (eg, resistance emergence and poor efficacy). Pimodivir is a first-in-class antiviral for influenza A under development for these patients. METHODS: Hospitalized patients with influenza A infection were randomized 2:1 to receive pimodivir 600 mg plus oseltamivir 75 mg or placebo plus oseltamivir 75 mg twice daily for 7 days in this phase 2b study. The primary objective was to compare pimodivir pharmacokinetics in elderly (aged 65-85 years) versus nonelderly adults (aged 18-64 years). Secondary end points included time to patient-reported symptom resolution. RESULTS: Pimodivir pharmacokinetic parameters in nonelderly and elderly patients were similar. Time to influenza symptom resolution was numerically shorter with pimodivir (72.45 hours) than placebo (94.15 hours). There was a lower incidence of influenza-related complications in the pimodivir group (7.9%) versus placebo group (15.6%). Treatment was generally well tolerated. CONCLUSIONS: No apparent relationship was observed between pimodivir pharmacokinetics and age. Our data demonstrate the need for a larger study of pimodivir in addition to oseltamivir to test whether it results in a clinically significant decrease in time-to-influenza-symptom alleviation and/or the frequency of influenza complications. CLINICAL TRIALS REGISTRATION: NCT02532283.