According to the findings of the AGILE trial, an 800 mg twice daily dose of molnupiravir can be safely used with good tolerability in people with early SARS-CoV-2 infection. In this phase I, open-label, dose-escalating, randomized controlled (standard-of-care) study, Saye H Khoo et al. investigated the  optimal dosage and safety of molnupiravir in individuals with early symptomatic infection.

The study enrolled people with polymerase chain reaction-confirmed SARS-CoV-2 infection within five days of symptom appearance. Of 103 people screened, 18 people were incorporated. Subjects were randomly segregated to either oral twice-daily administration of 300, 600 and 800 mg doses of molnupiravir for five days or control group. If the probability of 30% or higher dose-limiting toxicity (major endpoint) over controls was 25% or more, the dose was considered to be unsafe.

Clinical advancement, pharmacokinetics, safety and virological responses were the secondary endpoints. At 300, 600 and 800 mg doses, molnupiravir showed good tolerability without any serious noxious events. Table 1 shows the percentage of people who experienced at least 1 noxious event, all of which were reported to be mild (≤grade 2).

The likelihood of ≥30% excess toxicity over the controls at 800 mg was calculated at 0.9%. An 800 mg twice daily dose of molnupiravir for five days was suggested for Phase II assessment.