A dose-escalating, open-label, randomized-controlled Bayesian adaptive Phase I trial evaluated the safety and optimal dose of molnupiravir in subjects having an early symptomatic infection.

The adult subjects with PCR-confirmed SARS-CoV-2 infection within 5 days of symptom onset were enrolled and randomized 2:1 in groups to receive 300, 600 and 800 mg doses of molnupiravir by oral route, in a BD dose for 5 days or control. 

A dose was rendered unsafe if the probability of >/=30% dose-limiting toxicity over controls was >/=25%. 

Further safety, clinical progression, pharmacokinetics and virological responses were also assessed.

The following observations were made-

• 103 participants were screened for the study. 
• Molnupiravir showed good tolerability at all the investigated doses (300, 600 and 800 mg) without any severe adverse events. 
• Overall, 100% of 300mg and 600 mg, 25% of 800 mg molnupiravir receiving subjects and 83% of controls, suffered at least one adverse event, which was all mild (≤grade 2). 
• The probability of ≥30% excess toxicity than controls at 800 mg was calculated at 0.9%.

Thus the safety and tolerability of Molnupiravir were established and a dose of 800 mg twice daily for 5 days was guided for Phase II evaluation.

Source- Journal of Antimicrobial Chemotherapy, 2021;76(12):3286–3295, https://doi.org/10.1093/jac/dkab318