A Multipart Phase 1 Study to Assess Safety and Pharmacokinetics of Ibuzatrelvir in Healthy Participants and Dose Selection for a Dose-Ranging Study.

COVID-19 continues to be a threat to global health and a burden on healthcare systems. There is an ongoing need for COVID-19 antiviral therapies that are safe and effective across broad patient populations. Ibuzatrelvir is a potent, selective inhibitor of the SARS-CoV-2 main protease and demonstrated favorable properties for clinical development. We report safety, tolerability, and pharmacokinetic data for ibuzatrelvir from a phase 1 first-in-human study in healthy adults. Study parts evaluated ibuzatrelvir as single or multiple ascending doses, including analysis of participants in fasted and fed states, pharmacokinetics in Chinese and Japanese participants, relative bioavailability of crystalline tablet formulations, and dose selection for patients with COVID-19. Oral administration of ibuzatrelvir led to rapid absorption after all doses, and steady-state plasma concentrations were achieved by Day 2 for all doses. High-fat meals decreased maximum plasma concentration and area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration, but the concentration at 12 h postdose was comparable when administered without food. Exposures of ibuzatrelvir were similar between Chinese and non-Chinese participants, as well as between Japanese and non-Japanese participants. Ibuzatrelvir was safe and well-tolerated, with no serious or severe adverse events reported and no participants discontinuing. In conclusion, pharmacokinetics and safety were established for single-agent oral ibuzatrelvir, supporting the design and dose selection for further phase 2 trials and the continued development of ibuzatrelvir (NCT05580003).