Pharmacokinetics, safety, and simulated efficacy of an influenza treatment, baloxavir marboxil, in Chinese individuals

Abstract

Baloxavir marboxil is an endonuclease inhibitor indicated for the treatment of influenza in patients ≥12 years. No data exist for Chinese patients in global studies. This randomized, open-label, phase I study evaluated the pharmacokinetics (PK) and safety of baloxavir marboxil in healthy Chinese volunteers and was used to anticipate efficacy in Chinese patients. Patients received a single oral dose of baloxavir marboxil (40 or 80 mg [1:1]). Serial blood samples were collected predose and at various timepoints up to 14 days postdose. Baloxavir marboxil and acid plasma concentrations were determined by liquid chromatography tandem mass spectrometry. PK parameters of baloxavir acid were estimated by noncompartmental analysis. Adverse events (AEs) were recorded. Time to alleviation of symptoms (TTAS) was simulated for otherwise healthy (OwH) and high-risk (HR) Chinese and Asian patients. Thirty-two male patients received baloxavir marboxil. Baloxavir acid plasma concentration peaked 4 h postdose. Mean maximum concentration (Cmax ) was 107.6 and 206.9 ng/ml, and mean area under the plasma concentration-time curve from zero to infinity (AUC0-inf ) was 6955 and 9643 ng·h/ml in the 40 and 80 mg cohorts, respectively. AEs were mild and transient; no new safety signals were identified. Simulated median TTAS for OwH and HR Chinese patients agreed with simulated values in Asian patients. PK parameters were similar to Asian populations in other studies. The globally adopted baloxavir marboxil dosing strategy was consistent with the established safety profile of baloxavir marboxil in this population. Simulated efficacy indicated Chinese patients could benefit from similar efficacy to Asian patients.

Trial registration: ClinicalTrials.gov NCT03959332.

Conflict of interest statement

Y.L., J.J., Y.Z., and Y.W. were study investigators and declare no conflicts of interest. S.R., V.C., S.J., and S.D.B. are employees and shareholders of F. Hoffmann‐La Roche Ltd. V.D. was an employee of Certara while the study was conducted. Certara received funding from F. Hoffmann‐La Roche Ltd to conduct this study but were not paid for the development of this manuscript.

© 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.

Figures

FIGURE 1

Patient disposition

FIGURE 2

Mean baloxavir marboxil plasma concentration–time profiles for 40 and 80 mg dose cohorts. (a) Linear scale; (b) semilogarithmic scale