A Pharmacokinetics-Time to Alleviation of Symptoms Model to Support Extrapolation of Baloxavir Marboxil Clinical Efficacy in Different Ethnic Groups with Influenza A or B

Autor: Sylvie Retout, Stefan De Buck, Sébastien Jolivet, Vincent Duval, Valérie Cosson
Rok vydání: 2021
Předmět:
Zdroj: Clinical pharmacology and therapeutics. 112(2)
ISSN: 1532-6535
0295-4354
Popis: Baloxavir marboxil, the prodrug of baloxavir acid, is an anti-influenza antiviral. Here, a pharmacokinetics-time to alleviation of symptoms (PK-TTAS) model was developed and used to (I) characterize the PK-TTAS relationship, (II) quantify the impact of covariates, and (III) predict TTAS in different ethnic groups. Data from 1781 otherwise-healthy (OwH) or high-risk (HR) patients included in phase II (JapicCTI-153090) and III studies (NCT02954354 and NCT02949011) were used; patients received either placebo or oral baloxavir marboxil. The natural distribution of TTAS in placebo-treated patients was modeled, then TTAS data from the baloxavir marboxil arms were added to model the impact of baloxavir acid concentration on TTAS. PK parameters estimated by a population PK model and informed by phase I data (NCT03959332 and KCT0003535) were included to simulate TTAS in Chinese and South Korean patients. Composite symptom score at baseline (TSS0), ethnicity, sex, and patient type (OwH or HR) significantly impacted the natural TTAS distribution. TTAS reduced with increasing baloxavir acid concentrations. Compared with placebo, high and low baloxavir acid exposures (AUC
Databáze: OpenAIRE
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