Background and Objective <p>Obeldesivir is an orally administered prodrug of the nucleoside GS-441524. In&#xa0;vitro and preclinical studies have shown that obeldesivir can inhibit severe acute respiratory syndrome coronavirus 2, respiratory syncytial virus, and filoviruses with a high barrier to resistance. Prior population pharmacokinetic modeling has shown that certain factors, such as coronavirus disease 2019 (COVID-19), body weight, and renal function, can impact GS-441524 exposure. This study aimed to evaluate the pharmacokinetics and safety of obeldesivir in Japanese and white participants.</p> Methods <p>In this phase 1 study, healthy Japanese and white participants in the USA who were aged 18–65 years, were nonsmokers, had a body mass index of 18.0–30.0 kg/m<sup>2</sup>, and had normal renal/hepatic function were administered a single 350 mg oral dose of obeldesivir. Serial blood samples were collected up to 72 h postdose. Safety was assessed via physical examinations, clinical laboratory parameters, and treatment-emergent adverse events.</p> Conclusions <p>Plasma pharmacokinetic exposures of GS-441524 were higher in Japanese participants compared with white participants but were within the ranges observed in previous phase 1 studies. Differences in body weight between the populations in the study likely contributed to the increases in exposure. Obeldesivir was generally safe and well tolerated in both Japanese and white participants. These findings indicate that obeldesivir is likely to have favorable pharmacokinetic exposures and safety across different racial populations, supporting its potential use in treating multiple viral infections.</p>

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Pharmacokinetics, Safety, and Tolerability of Obeldesivir in Healthy Japanese and White Participants

  • Chi-Chi Peng,
  • Eric Salgado,
  • Jessica Corpus,
  • Santosh Davies,
  • Nancy Qi,
  • Yiannis Koullias,
  • Luzelena Caro

摘要

Background and Objective

Obeldesivir is an orally administered prodrug of the nucleoside GS-441524. In vitro and preclinical studies have shown that obeldesivir can inhibit severe acute respiratory syndrome coronavirus 2, respiratory syncytial virus, and filoviruses with a high barrier to resistance. Prior population pharmacokinetic modeling has shown that certain factors, such as coronavirus disease 2019 (COVID-19), body weight, and renal function, can impact GS-441524 exposure. This study aimed to evaluate the pharmacokinetics and safety of obeldesivir in Japanese and white participants.

Methods

In this phase 1 study, healthy Japanese and white participants in the USA who were aged 18–65 years, were nonsmokers, had a body mass index of 18.0–30.0 kg/m2, and had normal renal/hepatic function were administered a single 350 mg oral dose of obeldesivir. Serial blood samples were collected up to 72 h postdose. Safety was assessed via physical examinations, clinical laboratory parameters, and treatment-emergent adverse events.

Conclusions

Plasma pharmacokinetic exposures of GS-441524 were higher in Japanese participants compared with white participants but were within the ranges observed in previous phase 1 studies. Differences in body weight between the populations in the study likely contributed to the increases in exposure. Obeldesivir was generally safe and well tolerated in both Japanese and white participants. These findings indicate that obeldesivir is likely to have favorable pharmacokinetic exposures and safety across different racial populations, supporting its potential use in treating multiple viral infections.