tetano
Editor, Senior Moderator
J Infect Dis. 2018 Nov 14. doi: 10.1093/infdis/jiy547. [Epub ahead of print]
[h=1]Phase 2b Study of Pimodivir (JNJ-63623872) as Monotherapy or in Combination With Oseltamivir for Treatment of Acute Uncomplicated Seasonal Influenza A: TOPAZ Trial.[/h] Finberg RW[SUP]1[/SUP], Lanno R[SUP]2[/SUP], Anderson D[SUP]3[/SUP], Fleischhackl R[SUP]4[/SUP], van Duijnhoven W[SUP]5[/SUP], Kauffman RS[SUP]6[/SUP], Kosoglou T[SUP]3[/SUP], Vingerhoets J[SUP]7[/SUP], Leopold L[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]Background:[/h] Pimodivir, a first-in-class inhibitor of influenza virus polymerase basic protein 2, is being developed for hospitalized and high-risk patients with influenza A.
[h=4]Methods:[/h] In this double-blinded phase 2b study, adults with acute uncomplicated influenza A were randomized 1:1:1:1 to receive one of the following treatments twice daily for 5 days: placebo, pimodivir 300 mg or 600 mg, or pimodivir 600 mg plus oseltamivir 75 mg. Antiviral activity, safety, and pharmacokinetics of pimodivir alone or in combination were evaluated.
[h=4]Results:[/h] Of 292 patients randomized, 223 were treated and had confirmed influenza A virus infection. The trial was stopped early because the primary end point was met; the area under the curve of the viral load, determined by quantitative reverse transcription-polymerase chain reaction analysis, in nasal secretions from baseline to day 8 significantly decreased in the active treatment groups, compared with the placebo group (300 mg group, -3.6 day*log10 copies/mL [95% confidence interval {CI}, -7.1 to -0.1]; 600 mg group, -4.5 [95%CI -8.0 to -1.0]; and combination group, -8.6 [95% CI, -12.0 to -5.1]). Pimodivir plus oseltamivir yielded a significantly lower viral load titer over time than placebo and a trend for a shorter time to symptom resolution than placebo. Pimodivir plasma concentrations increased in a dose-proportional manner. The most commonly reported adverse event was mild or moderate diarrhea.
[h=4]Conclusions:[/h] Pimodivir (with or without oseltamivir) resulted in significant virologic improvements over placebo, demonstrated trends in clinical improvement, and was well tolerated. Pimodivir 600 mg twice daily is in further development.
[h=4]Clinical Trials Registration:[/h] NCT02342249, 2014-004068-39, and CR107745.
PMID: 30428049 DOI: 10.1093/infdis/jiy547
[h=1]Phase 2b Study of Pimodivir (JNJ-63623872) as Monotherapy or in Combination With Oseltamivir for Treatment of Acute Uncomplicated Seasonal Influenza A: TOPAZ Trial.[/h] Finberg RW[SUP]1[/SUP], Lanno R[SUP]2[/SUP], Anderson D[SUP]3[/SUP], Fleischhackl R[SUP]4[/SUP], van Duijnhoven W[SUP]5[/SUP], Kauffman RS[SUP]6[/SUP], Kosoglou T[SUP]3[/SUP], Vingerhoets J[SUP]7[/SUP], Leopold L[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]Background:[/h] Pimodivir, a first-in-class inhibitor of influenza virus polymerase basic protein 2, is being developed for hospitalized and high-risk patients with influenza A.
[h=4]Methods:[/h] In this double-blinded phase 2b study, adults with acute uncomplicated influenza A were randomized 1:1:1:1 to receive one of the following treatments twice daily for 5 days: placebo, pimodivir 300 mg or 600 mg, or pimodivir 600 mg plus oseltamivir 75 mg. Antiviral activity, safety, and pharmacokinetics of pimodivir alone or in combination were evaluated.
[h=4]Results:[/h] Of 292 patients randomized, 223 were treated and had confirmed influenza A virus infection. The trial was stopped early because the primary end point was met; the area under the curve of the viral load, determined by quantitative reverse transcription-polymerase chain reaction analysis, in nasal secretions from baseline to day 8 significantly decreased in the active treatment groups, compared with the placebo group (300 mg group, -3.6 day*log10 copies/mL [95% confidence interval {CI}, -7.1 to -0.1]; 600 mg group, -4.5 [95%CI -8.0 to -1.0]; and combination group, -8.6 [95% CI, -12.0 to -5.1]). Pimodivir plus oseltamivir yielded a significantly lower viral load titer over time than placebo and a trend for a shorter time to symptom resolution than placebo. Pimodivir plasma concentrations increased in a dose-proportional manner. The most commonly reported adverse event was mild or moderate diarrhea.
[h=4]Conclusions:[/h] Pimodivir (with or without oseltamivir) resulted in significant virologic improvements over placebo, demonstrated trends in clinical improvement, and was well tolerated. Pimodivir 600 mg twice daily is in further development.
[h=4]Clinical Trials Registration:[/h] NCT02342249, 2014-004068-39, and CR107745.
PMID: 30428049 DOI: 10.1093/infdis/jiy547