Phase 1 First-in-Human, Single- and Multiple-Ascending Dose, and Food Effect Studies to Assess the Safety, Tolerability, and Pharmacokinetics of Presatovir for the Treatment of Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV)-associated respiratory tract infection is a leading cause of hospitalizations in infants for which no effective treatment exists. RSV infection is also an important cause of respiratory disease in adults and immunocompromised patients. Presatovir (GS-5806) is an orally bioavailable antiviral agent that inhibits fusion of RSV with host cell membranes. Here, results from 2 phase 1 studies that evaluated safety, tolerability, and pharmacokinetics of presatovir in healthy adults following administration of single and multiple (7 days) once- or twice-daily ascending doses (first-in-human study) and in the presence or absence of food (food effect study) are described. Presatovir exhibited favorable safety and pharmacokinetic profiles that supported once-daily dosing. Presatovir exposure increased in an approximately dose-proportional manner across the evaluated dose range (single doses 25-300 mg; multiple doses 10-75 mg once daily for 7 days). Administration of presatovir with a high-fat meal did not alter exposure, supporting administration without regard to a meal in further clinical studies. These data were subsequently used to inform presatovir dosing regimens in a phase 2a challenge study of adults experimentally infected with RSV. Collectively, results from phase 1 evaluations and a phase 2a challenge study support further clinical investigation of presatovir for the treatment of RSV infection.