tetano
Editor, Senior Moderator
J Infect Dis
. 2020 Jun 30;jiaa376.
doi: 10.1093/infdis/jiaa376. Online ahead of print.
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 O'Neil[SUP] 1 [/SUP], Michael G Ison[SUP] 2 [/SUP], Marie-Charlotte Hallouin-Bernard[SUP] 3 [/SUP], Anna C Nilsson[SUP] 4 [/SUP], Antoni Torres[SUP] 5 [/SUP], John M Wilburn[SUP] 1 [/SUP], Wilbert van Duijnhoven[SUP] 6 [/SUP], Ilse Van Dromme[SUP] 6 [/SUP], David Anderson[SUP] 7 [/SUP], Sofie Deleu[SUP] 6 [/SUP], Teddy Kosoglou[SUP] 7 [/SUP], Johan Vingerhoets[SUP] 6 [/SUP], Stefaan Rossenu[SUP] 6 [/SUP], Lorant Leopold[SUP] 7 [/SUP]
AffiliationsExpand
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 non-elderly adults (aged 18-64 years). Secondary endpoints included time-to-patient-reported symptom resolution.
Results: Pimodivir pharmacokinetic parameters in non-elderly 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.
Keywords: Pimodivir; clinical trial; duration of symptoms; elderly; hospitalized; influenza A virus; influenza complications; oseltamivir; pharmacokinetics; viral clearance.
. 2020 Jun 30;jiaa376.
doi: 10.1093/infdis/jiaa376. Online ahead of print.
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 O'Neil[SUP] 1 [/SUP], Michael G Ison[SUP] 2 [/SUP], Marie-Charlotte Hallouin-Bernard[SUP] 3 [/SUP], Anna C Nilsson[SUP] 4 [/SUP], Antoni Torres[SUP] 5 [/SUP], John M Wilburn[SUP] 1 [/SUP], Wilbert van Duijnhoven[SUP] 6 [/SUP], Ilse Van Dromme[SUP] 6 [/SUP], David Anderson[SUP] 7 [/SUP], Sofie Deleu[SUP] 6 [/SUP], Teddy Kosoglou[SUP] 7 [/SUP], Johan Vingerhoets[SUP] 6 [/SUP], Stefaan Rossenu[SUP] 6 [/SUP], Lorant Leopold[SUP] 7 [/SUP]
AffiliationsExpand
- PMID: 32604406
- DOI: 10.1093/infdis/jiaa376
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 non-elderly adults (aged 18-64 years). Secondary endpoints included time-to-patient-reported symptom resolution.
Results: Pimodivir pharmacokinetic parameters in non-elderly 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.
Keywords: Pimodivir; clinical trial; duration of symptoms; elderly; hospitalized; influenza A virus; influenza complications; oseltamivir; pharmacokinetics; viral clearance.