Optimal Dose and Safety of Intravenous Favipiravir in Hospitalized Patients With COVID-19: A Dose-Escalating, Randomized Controlled Phase Ib Study

Collapse authors list.
Rowland, Tim, Fitzgerald, Richard, Challenger, Elizabeth ORCID: 0000-0002-8978-6067, Dickinson, Laura ORCID: 0000-0001-5557-9396, Else, Laura J, Walker, Lauren ORCID: 0000-0002-3827-4387, Hale, Colin, Shaw, Victoria ORCID: 0000-0002-0429-0186, Kelly, Callum, Lyon, Rebecca et al (show 22 more authors) , Gibney, Jennifer, Dhamani, Karim, Irwin, Margaret, Enever, Yvanne, Tetlow, Michelle, Wood, William ORCID: 0000-0003-0683-8085, Reynolds, Helen ORCID: 0000-0001-7443-4520, Chiong, Justin ORCID: 0000-0001-8063-6399, Osanlou, Orod, Pertinez, Henry ORCID: 0009-0004-4522-9201, Bullock, Katie ORCID: 0000-0002-5758-0179, Greenhalf, William ORCID: 0000-0002-1865-3195, Owen, Andrew ORCID: 0000-0002-9819-7651, Lalloo, David G, Jacobs, Michael, Hiscox, Julian A ORCID: 0000-0002-6582-0275, Jaki, Thomas, Mozgunov, Pavel, Saunders, Geoffrey, Griffiths, Gareth, Khoo, Saye H ORCID: 0000-0002-2769-0967 and Fletcher, Thomas E (2026) Optimal Dose and Safety of Intravenous Favipiravir in Hospitalized Patients With COVID-19: A Dose-Escalating, Randomized Controlled Phase Ib Study CLINICAL PHARMACOLOGY & THERAPEUTICS, 119 (6). pp. 1650-1661. ISSN 0009-9236, 1532-6535

Access the full-text of this item by clicking on the Open Access link.

Abstract

AGILE (NCT04746183) is a Phase Ib/IIa platform, evaluating candidates to treat COVID-19. Candidate Specific Trial 6 evaluated the safety and optimal dose of a novel intravenous formulation of favipiravir in a dose-escalating, open-label, randomized, controlled, Bayesian adaptive Phase Ib trial. Hospitalized adults with PCR-confirmed SARS-CoV-2 infection, within 14 days of symptomatic COVID-19 were randomized 2:1 in groups of 6 (n = 4 favipiravir, n = 2 standard of care) to ascending doses of intravenous favipiravir twice daily (b.i.d.) for 7 days or standard of care. Clinical data, safety evaluations, virology and pharmacokinetic samples were collected. The primary outcome was safety. Secondary outcomes included clinical, pharmacokinetic and virological endpoints. Twenty-four participants enrolled between September 10, 2022 and November 1, 2023 [10/24 female; median age 74 years (range 52–93)]. Favipiravir was well tolerated despite a high background rate of unrelated adverse events. No dose limiting toxicities were observed, with a model-predicted dose limiting toxicity risk of 16.8% and probability of unacceptable toxicity of 2.7% at the highest dose level. No serious adverse events were deemed related to favipiravir but an expected association with asymptomatic, transient hyperuricemia was observed. Favipiravir exposures increased disproportionally to dose with significant accumulation in plasma, but with marked variability between participants within each cohort. This novel formulation of favipiravir was safe at sustained high doses that reached pre-specified pharmacokinetic targets in a study group with frailty and complex health profiles. We consider doses up to 2,400 mg b.i.d. to be safe for further evaluation.

Item Type:	Article
Uncontrolled Keywords:	AGILE CST‐6 Study Group, Humans, Amides, Pyrazines, Antiviral Agents, Hospitalization, Bayes Theorem, Dose-Response Relationship, Drug, Aged, Aged, 80 and over, Middle Aged, Female, Male, Administration, Intravenous, COVID-19, SARS-CoV-2, COVID-19 Drug Treatment
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Clinical Directorate Faculty of Health & Life Sciences > Clinical Directorate > Clinical Directorate Prof Svcs Faculty of Health & Life Sciences > Inst. Infection, Vet & Ecological Sciences Faculty of Health & Life Sciences > Inst. Infection, Vet & Ecological Sciences > Clinical Infection, Microbiology & Immunology Faculty of Health & Life Sciences > Inst. Infection, Vet & Ecological Sciences > Infection Biology & Microbiomes Faculty of Health & Life Sciences > Inst. Infection, Vet & Ecological Sciences > Inst. Infection, Vet & Ecological Sciences (T&R Staff) Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology (T&R Staff) Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Molecular & Clinical Cancer Medicine Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Pharmacology & Therapeutics Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > SMIB Professional Services
Depositing User:	Symplectic Admin
Date Deposited:	13 Aug 2026 09:51
Last Modified:	13 Aug 2026 09:51
DOI:	10.1002/cpt.70261
Open Access URL:	https://doi.org/10.1002/cpt.70261
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3199922
Disclaimer:	The University of Liverpool is not responsible for content contained on other websites from links within repository metadata. Please contact us if you notice anything that appears incorrect or inappropriate.