Clinical efficacy and safety of the selective oral neuraminidase inhibitor oseltamivir in treating acute influenza--placebo-controlled double-blind multicenter phase III trial

We conducted the placebo-controlled double-blind multicenter Phase III trial of newly developed selective oral neuraminidase inhibitor, oseltamivir phosphate (Ro64-0796), in order to evaluate the efficacy and safety, when Ro64-0796 was administered orally to both type A and type B influenzavirus infected patients. Patients were randomly assigned to either Ro64-0796 75 mg twice daily group or matching placebo group for five days. A total of 316 patients (Ro64-0796 group; 154 and placebo group; 162) were recruited, and intent-to-treat infected population, which was defined as the patients that study drug was administered one or more and laboratory-confirmed influenzavirus infection was demonstrated, were 122 and 130, respectively. Ro64-0796 decreased significantly median viral titers after 72 hours (p = 0.0009. Analysis of covariance), indicating the rapid inhibition of virus replication, and duration of illness which was primary variable of efficacy, was reduced statistically significant by one day (23.3 hours) (p = 0.0216, generalized Wilcoxon test). Ro64-0796 treatment also resulted in the reduction of the fever duration and severity of clinical symptoms. Concerning the safety evaluation, the main accompanied symptoms with Ro64-0796 application were gastrointestinal disorders such as bellyache, nausea and vomiting. Most of these events were mild and allowable for the clinical use. There was no abnormal change attributable to Ro64-0796 application in the clinical laboratory tests as well as the physiological tests. Our data suggests that Ro64-0796 is useful in treating the acute influenzavirus infection.