A Five-in-One First-in-Human Study To Assess Safety, Tolerability, and Pharmacokinetics of RO7049389, an Inhibitor of Hepatitis B Virus Capsid Assembly, after Single and Multiple Ascending Doses in Healthy Participants

= 42). A single doses of 450 mg RO7049389 was administered under fasted and fed condition. The microdose of midazolam was administered before and after multiple dosing of RO7049389. Safety and tolerability were monitored throughout the study. Serial blood and urine samples were collected for the PK analysis. RO7049389 was safe and well tolerated in healthy participants. Absorption and elimination of RO7049389 occurred rapidly in plasma with minimal recovery in urine. Greater than dose-proportional increases in plasma exposure were observed. Exposure of RO7049389 (450 mg) increased by ∼2-fold when administered with a high-fat meal. The inhibition effect of RO7049389 on CYP3A was weak (<20%). No effect on QT interval was observed at up to a single dose of 2,500 mg. RO7049389 displayed a favorable safety, tolerability and PK profile suitable for further clinical development. (This trial was registered at ClinicalTrials.gov with the identifier NCT02952924.).