A Pharmacokinetics Study of Favipiravir in Patients With Severe Influenza

Summary

Title: An adaptive study of the pharmacokinetics of favipiravir in patients with severe influenza Study Design: An open label, single group assignment, adaptive study to evaluate the pharmacokinetics of favipiravir in adult patients with severe influenza. In the first stage, participants will receive favipiravir 1600mg BID on day 1, followed by favipiravir 600mg BID for 9 days. If the proportion of patients with a minimum observed plasma trough concentration above the MEC (20μg/ml) at all measured time points after the second dose is less than 80% then a second patient cohort will be recruited and will receive favipiravir 1800mg BID on day 1, followed by favipiravir 800mg BID for 9 days. Intervention: The 1st stage: 1600mg BID on day 1, followed with 600mg BID for 9 days. Sample size: 15 The 2nd stage: 1800mg BID on day 1, followed with 800mg BID for 9 days. Sample size: 15 Population: Males and females aged 18 years or older admitted to hospital with a positive PCR test for influenza and a PaO2/FiO2≤300mmHg or/and on mechanical ventilation for severe lung infection on admission. Sample size 15 or 30 severe influenza patients Research hypothesis The administration of oral favipiravir at either 1600mg/600mg BID or 1800/800mg BID will result in ≥ 80% patients achieving a minimum observed plasma trough concentration above the MEC (20μg/ml) at all measured time points after the second dose. Phase: Phase 2a, PK, safety and feasibility study. Description of Study Agent: Favipiravir (T-705) a viral RNA-dependent RNA polymerase inhibitor. Study Duration: 1 year Participant Duration: 38 days

Timeline

Start

2018-02-06

Primary completion

2019-02-20

Completion

2019-03-27

Publications

• Results Gao HN, Lu HZ, Cao B, Du B, Shang H, Gan JH, Lu SH, Yang YD, Fang Q, Shen YZ, Xi XM, Gu Q, Zhou XM, Qu HP, Yan Z, Li FM, Zhao W, Gao ZC, Wang GF, Ruan LX, Wang WH, Ye J, Cao HF, Li XW, Zhang WH, Fang XC, He J, Liang WF, Xie J, Zeng M, Wu XZ, Li J, Xia Q, Jin ZC, Chen Q, Tang C, Zhang ZY, Hou BM, Feng ZX, Sheng JF, Zhong NS, Li LJ. Clinical findings in 111 cases of influenza A (H7N9) virus infection. N Engl J Med. 2013 Jun 13;368(24):2277-85. doi: 10.1056/NEJMoa1305584. Epub 2013 May 22.
• Results Zheng S, Tang L, Gao H, Wang Y, Yu F, Cui D, Xie G, Yang X, Zhang W, Ye X, Zhang Z, Wang X, Yu L, Zhang Y, Yang S, Liang W, Chen Y, Li L. Benefit of Early Initiation of Neuraminidase Inhibitor Treatment to Hospitalized Patients With Avian Influenza A(H7N9) Virus. Clin Infect Dis. 2018 Mar 19;66(7):1054-1060. doi: 10.1093/cid/cix930.
• Results Li H, Yang SG, Gu L, Zhang Y, Yan XX, Liang ZA, Zhang W, Jia HY, Chen W, Liu M, Yu KJ, Xue CX, Hu K, Zou Q, Li LJ, Cao B, Wang C; National Influenza A(H1N1)pdm09 Clinical Investigation Group of China. Effect of low-to-moderate-dose corticosteroids on mortality of hospitalized adolescents and adults with influenza A(H1N1)pdm09 viral pneumonia. Influenza Other Respir Viruses. 2017 Jul;11(4):345-354. doi: 10.1111/irv.12456. Epub 2017 Jun 9.
• Results Wang X, Jiang H, Wu P, Uyeki TM, Feng L, Lai S, Wang L, Huo X, Xu K, Chen E, Wang X, He J, Kang M, Zhang R, Zhang J, Wu J, Hu S, Zhang H, Liu X, Fu W, Ou J, Wu S, Qin Y, Zhang Z, Shi Y, Zhang J, Artois J, Fang VJ, Zhu H, Guan Y, Gilbert M, Horby PW, Leung GM, Gao GF, Cowling BJ, Yu H. Epidemiology of avian influenza A H7N9 virus in human beings across five epidemics in mainland China, 2013-17: an epidemiological study of laboratory-confirmed case series. Lancet Infect Dis. 2017 Aug;17(8):822-832. doi: 10.1016/S1473-3099(17)30323-7. Epub 2017 Jun 2.
• Results Dunning J, Baillie JK, Cao B, Hayden FG; International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). Antiviral combinations for severe influenza. Lancet Infect Dis. 2014 Dec;14(12):1259-70. doi: 10.1016/S1473-3099(14)70821-7. Epub 2014 Sep 8.
• Results Kumar A. Early versus late oseltamivir treatment in severely ill patients with 2009 pandemic influenza A (H1N1): speed is life. J Antimicrob Chemother. 2011 May;66(5):959-63. doi: 10.1093/jac/dkr090. Epub 2011 Mar 15.
• Results Kile JC, Ren R, Liu L, Greene CM, Roguski K, Iuliano AD, Jang Y, Jones J, Thor S, Song Y, Zhou S, Trock SC, Dugan V, Wentworth DE, Levine MZ, Uyeki TM, Katz JM, Jernigan DB, Olsen SJ, Fry AM, Azziz-Baumgartner E, Davis CT. Update: Increase in Human Infections with Novel Asian Lineage Avian Influenza A(H7N9) Viruses During the Fifth Epidemic - China, October 1, 2016-August 7, 2017. MMWR Morb Mortal Wkly Rep. 2017 Sep 8;66(35):928-932. doi: 10.15585/mmwr.mm6635a2.

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