BACKGROUND:SHEN26, an oral broad-spectrum antiviral drug, possesses potent preclinical activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has a favorable safety profile.
METHODS:We report safety, tolerability, and pharmacokinetic data from a randomized, double-blind, placebo-controlled phase I study of SHEN26. Eighty-six healthy subjects were enrolled in the three studies: a single ascending-dose study (SAD), a multiple ascending-dose study (MAD), and a food-effect study (FE).
RESULTS:In the SAD trial, the maximum observed plasma concentration (Cmax) and area under the curve (AUC) of the SHEN26 rapid metabolite SHEN26-69-0 increased approximately dose-proportionally in the 50-400 mg fasting dose range. In the 800 mg dose group, standard meals increased the Cmax and AUC of SHEN26-69-0. In the MAD trial, the accumulation ratios of Cmax and AUC indicated slight accumulation upon repeated SHEN26 dosing. In the FE trial, a high-fat meal prolonged the time to maximum plasma concentration (Tmax) and increased the Cmax and AUC of SHEN26-69-0 compared with fasting administration. Most treatment-related adverse events were mild and resolved without treatment.
CONCLUSION:SHEN26 demonstrated satisfactory safety and tolerability in healthy subjects, which supports the continued study of SHEN26 against SARS-CoV-2.
TRIAL REGISTRATION:The trial is registered in ClinicalTrials.gov (CT. gov identifier: NCT05504746).