Safety, Tolerability, and Pharmacokinetics of EGT710, a Novel Coronavirus M pro Inhibitor, in Healthy Adults: A Randomized, Single‐ and Multiple‐Dose Study
Jart A. F. Oosterhaven, Jonathan Trolander, Lidiya Bebrevska, Hilmar Schiller, Begum Alaybeyoglu, Suzanne Gaudet, Allison Claas, Kamal Kumar Balavenkatraman, Renee Bergeron, Fernanda V. Duraes, Frederique Chaperon, Swati Ghanshani, Elisabete Goncalves, Steven J. KovacsAbstract
Antiviral therapy is needed to address acute coronavirus disease. EGT710 is a novel low‐molecular‐weight inhibitor of the coronavirus main protease (M pro ). This first‐in‐human study evaluated the safety, tolerability, and pharmacokinetics of EGT710 in healthy adults. The study conducted in the Netherlands involved three parts: a blinded, placebo‐controlled, 3:1 randomized, single ascending dose Part A (n = 39); a multiple ascending dose Part B (n = 31); and an open‐label, three‐period, six sequence, randomized, cross‐over Part C (n = 18) to evaluate food and formulation effects on EGT710 bioavailability. EGT710 was well tolerated. All adverse events (AEs) were mild (Grade 1), with no serious AEs or discontinuations. Aside from mild gastrointestinal AEs associated with EGT710, AE frequency was similar between groups with no dose‐dependent or dose‐limiting adverse effects. EGT710 was rapidly absorbed (median T max 2.0 h), showed sub‐proportional AUC and C max increases and no significant accumulation with daily dosing. Bioavailability was comparable between suspension and capsule formulations. Food increased C max by 20% and AUC by 27%. EGT710 700 mg once daily for 7 days modestly induced CYP3A4 activity but had no effect on organic anion transporting polypeptide (OAT1/3) activity. Oral EGT710 (capsule and suspension) was safe and well tolerated, with pharmacokinetics that support further development as a treatment for coronavirus disease.