[Objective]
Molnupiravir (MOV) is a prodrug of the ribonucleoside analog, N-hydroxycytidine (NHC), that inhibits replication of RNA viruses including SARS-CoV-2 and is the first approved oral COVID-19 therapy for emergency use in Japan. In this study, safety and pharmacokinetics following single (SD) and multiple dose (MD)administration of MOV were assessed. This presentation focuses on the study design and safety results.
[Method]
This Ph1 study was a 2-part (SD and MD), randomized, placebo-controlled, double-blind study in Japanese healthy male participants, which was conducted with adaptive planning where the study design is optimized depending on the ongoing global Ph2/3 study (MOVe-OUT study).
In the SD part, 4 out of a planned 5 doses of MOV from 100, 200, 400, 800 and/or 1600 mg in the fasted state along with the dose at 400 or 800 mg in the fed state were adaptively selected based on emerging results from MOVe-OUT study. In the MD part, 2 of 3 dose regimens of 200, 400 and/or 800 mg every 12 hours (Q12H) for 5.5 days were also adaptively selected, with a relatively larger sample size (n=20/panel) than a typical Ph1 study. Throughout the study, safety was evaluated by adverse events.
[Result and Discussion]
Based on emerging results of the parallel-conducted MOVe-OUT phase 2 portion, the dose level of 800 mg administered Q12H for 5 days was selected for evaluation in Ph3. This decision was the basis of the selection of the following doses of MOV in this study: 200, 400, 800 and 1600 mg for SD; 800 mg SD for food effect evaluation; 400 and 800 mg Q12H for MD. All adverse events (AE) were mild to moderate in intensity. No serious AEs were reported.
[Conclusion]
SD and MD of MOV were generally well tolerated in Japanese healthy male participants. Employing adaptive planning for study design and acquiring safety data in Japanese participants were essential to support special approval in Japan in response to urgent unmet medical need for COVID-19 oral therapies.