Pharmacokinetics and Safety of Single and Multiple Doses of Molnupiravir in Healthy Male Chinese Adults: An Open‐Label, Fixed Sequence, Phase 1 Study

Molnupiravir is an orally administered prodrug of β-D-N4-hydroxycytidine (NHC) that is conditionally approved in China for the treatment of mild to moderate COVID-19 in nonhospitalized adults at high risk of disease progression. Molnupiravir is rapidly absorbed and hydrolyzed to deliver NHC into systemic circulation. An open-label, fixed-sequence, Phase 1 study was conducted to evaluate the tolerability, safety, and pharmacokinetics (PK) following single and multiple (every 12 h for 5.5 days) oral dosing of molnupiravir 800 mg in 16 healthy, male Chinese participants. After multiple doses of molnupiravir, the median time to maximum concentration was 2.0 h for plasma NHC. NHC concentrations generally decreased in a biphasic manner, with a terminal half-life of 21.9 h, and NHC exposures (i.e., area under the curve and maximum plasma concentration) were similar following single and multiple doses of molnupiravir. No accumulation of NHC in plasma was observed. When compared with historical data from published clinical trials of similar study design, NHC exposure in Chinese participants was marginally higher than that in non-Asian participants but remained within established clinical bounds. Overall, molnupiravir was generally well-tolerated. Ten participants (63.5%) experienced at least one adverse event throughout the study, the severity of which was mild or moderate, and none led to treatment discontinuation. There were no clinically meaningful findings in other safety evaluations. These data support use of the standard 5-day regimen of molnupiravir 800 mg every 12 h without dose adjustment for the treatment of COVID-19 in the Chinese population.