tetano
Editor, Senior Moderator
Expert Opin Investig Drugs
. 2024 Apr 25.
doi: 10.1080/13543784.2024.2347302. Online ahead of print. 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
Cheng Sun[SUP] 1 2 [/SUP], Hao Liu[SUP] 1 2 [/SUP], Ziwei Ouyang[SUP] 1 2 [/SUP], Jie Ding[SUP] 1 [/SUP], Qin Zhang[SUP] 1 [/SUP], Hongjie Ma[SUP] 3 [/SUP], Dandan Xu[SUP] 3 [/SUP], Qian Zhang[SUP] 1 [/SUP], Renpeng Zhou[SUP] 1 [/SUP], Mingming Yang[SUP] 3 [/SUP], Wei Hu[SUP] 1 [/SUP]
Affiliations
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[SUB]max[/SUB]) 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 C[SUB]max[/SUB] and AUC of SHEN26-69-0. In the MAD trial, the accumulation ratios of C[SUB]max[/SUB] and AUC indicated slight accumulation upon repeated SHEN26 dosing. In the FE trial, a high-fat meal prolonged the time to maximum plasma concentration (T[SUB]max[/SUB]) and increased the C[SUB]max[/SUB] 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).
Keywords: Food effects; Pharmacokinetics; SHEN26; Safety; Tolerability.
. 2024 Apr 25.
doi: 10.1080/13543784.2024.2347302. Online ahead of print. 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
Cheng Sun[SUP] 1 2 [/SUP], Hao Liu[SUP] 1 2 [/SUP], Ziwei Ouyang[SUP] 1 2 [/SUP], Jie Ding[SUP] 1 [/SUP], Qin Zhang[SUP] 1 [/SUP], Hongjie Ma[SUP] 3 [/SUP], Dandan Xu[SUP] 3 [/SUP], Qian Zhang[SUP] 1 [/SUP], Renpeng Zhou[SUP] 1 [/SUP], Mingming Yang[SUP] 3 [/SUP], Wei Hu[SUP] 1 [/SUP]
Affiliations
- PMID: 38662639
- DOI: 10.1080/13543784.2024.2347302
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[SUB]max[/SUB]) 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 C[SUB]max[/SUB] and AUC of SHEN26-69-0. In the MAD trial, the accumulation ratios of C[SUB]max[/SUB] and AUC indicated slight accumulation upon repeated SHEN26 dosing. In the FE trial, a high-fat meal prolonged the time to maximum plasma concentration (T[SUB]max[/SUB]) and increased the C[SUB]max[/SUB] 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).
Keywords: Food effects; Pharmacokinetics; SHEN26; Safety; Tolerability.