1. Safety, tolerability, and pharmacokinetics of the novel RdRp inhibitor SHEN26 against SARS-CoV-2: a randomized, placebo-controlled, double-blind Phase I study in healthy subjects.
- Author
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Sun C, Liu H, Ouyang Z, Ding J, Zhang Q, Ma H, Xu D, Zhang Q, Zhou R, Yang M, and Hu W
- Subjects
- Humans, Double-Blind Method, Male, Adult, Female, Young Adult, Middle Aged, Area Under Curve, COVID-19 Drug Treatment, Healthy Volunteers, COVID-19, Antiviral Agents pharmacokinetics, Antiviral Agents adverse effects, Antiviral Agents administration & dosage, Antiviral Agents pharmacology, Dose-Response Relationship, Drug, SARS-CoV-2, Food-Drug Interactions
- Abstract
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 (C
max ) 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).- Published
- 2024
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