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Candidate Specific Trial 6 evaluated the safety and optimal dose of a novel intravenous formulation of favipiravir in a dose\u2010escalating, open\u2010label, randomized, controlled, Bayesian adaptive Phase Ib trial. Hospitalized adults with PCR\u2010confirmed SARS\u2010CoV\u20102 infection, within 14\u2009days of symptomatic COVID\u201019 were randomized 2:1 in groups of 6 (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20094 favipiravir,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20092 standard of care) to ascending doses of intravenous favipiravir twice daily (b.i.d.) for 7\u2009days 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\u2010four participants enrolled between September 10, 2022 and November 1, 2023 [10\/24 female; median age 74\u2009years (range 52\u201393)]. Favipiravir was well tolerated despite a high background rate of unrelated adverse events. No dose limiting toxicities were observed, with a model\u2010predicted 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\u2010specified pharmacokinetic targets in a study group with frailty and complex health profiles. We consider doses up to 2,400\u2009mg b.i.d. to be safe for further evaluation.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70261","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T15:29:41Z","timestamp":1773847781000},"page":"1650-1661","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Optimal Dose and Safety of Intravenous Favipiravir in Hospitalized Patients With\n                    <scp>COVID<\/scp>\n                    \u201019: A Dose\u2010Escalating, Randomized Controlled Phase Ib Study"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5059-065X","authenticated-orcid":false,"given":"Tim","family":"Rowland","sequence":"first","affiliation":[{"name":"Liverpool School of Tropical Medicine  Liverpool UK"},{"name":"Liverpool University Hospitals Foundation Trust  Liverpool 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Pharmacology and Therapeutics, Institute of Integrative, Systems and Molecular Biology, Centre for Experimental Therapeutics (TherEx) University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0078-3294","authenticated-orcid":false,"given":"Laura J.","family":"Else","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Institute of Integrative, Systems and Molecular Biology, Centre for Experimental Therapeutics (TherEx) University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3827-4387","authenticated-orcid":false,"given":"Lauren","family":"Walker","sequence":"additional","affiliation":[{"name":"Liverpool University Hospitals Foundation Trust  Liverpool UK"},{"name":"NIHR Liverpool Clinical Research Facility  Liverpool 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