Efficacy and safety of favipiravir, an oral RNA-dependent RNA polymerase inhibitor, in mild-to-moderate COVID-19: A randomized, comparative, open-label, multicenter, phase 3 clinical trial
Zarir F Udwadia, Pawan Singh, Hanmant Barkate, Saiprasad Patil, Shabbir Rangwala, Amol Pendse, Jatin Kadam, Wen Wu, Cynthia F Caracta, Monika Tandon
International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.11.142
To assess the efficacy and safety of favipiravir in adults with mild-to-moderate coronavirus disease 2019 . Methods: In this randomized, open-label, parallel-arm, multicenter, phase 3 trial, adults (18-75 years) with RT-PCR confirmed COVID-19 and mild-to-moderate symptoms (including asymptomatic) were randomized 1:1 to oral favipiravir (day 1: 1800 mg BID and days 2À14: 800 mg BID) plus standard supportive care versus supportive care alone. The primary endpoint was time to the cessation of viral shedding; time to clinical cure was also measured. Results: From May 14 to July 3, 2020, 150 patients were randomized to favipiravir (n = 75) or control (n = 75). Median time to the cessation of viral shedding was 5 days (95% CI: 4 days, 7 days) versus 7 days (95% CI: 5 days, 8 days), P = 0.129, and median time to clinical cure was 3 days (95% CI: 3 days, 4 days) versus 5 days (95% CI: 4 days, 6 days), P = 0.030, for favipiravir and control, respectively. Adverse events were observed in 36% of favipiravir and 8% of control patients. One control patient died due to worsening disease.
Conclusion: The lack of statistical significance on the primary endpoint was confounded by limitations of the RT-PCR assay. Significant improvement in time to clinical cure suggests favipiravir may be beneficial in mild-to-moderate COVID-19.
Conflict of interest Monika Tandon, Pawan Singh, Hanmant Barkate, Saiprasad Patil, Shabbir Rangwala, Amol Pendse, and Jatin Kadam are fulltime employees of Glenmark Pharmaceuticals Limited, India. Wen Wu is a full-time employee of Glenmark Pharmaceuticals Ltd, United Kingdom. Cynthia Caracta is a full-time employee of Glenmark Pharmaceuticals Inc., USA. Zarir F Udwadia received an investigator grant from Glenmark Pharmaceuticals Limited, India, as a site principal investigator for this study.
Ethical approval The protocol and informed consent form were approved by institutional/independent ethics committees and the Drugs Controller General of India (April 26, 2020) . The trial was undertaken in accordance with current guidelines of the Central Drugs Standard Control Organization, which is the National Regulatory Authority in India, the International Conference on Harmonization Good Clinical Practice, and the Declaration of Helsinki. All patients provided written informed consent.
Contributions Author contributions: All authors contributed equally to this report. Zarir F Udwadia, Monika Tandon, Pawan Singh, Hanmant Barkate, Shabbir Rangwala, Amol Pendse, and Wen Wu had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Monika Tandon, Pawan Singh, Hanmant Barkate, Saiprasad Patil, and Wen Wu. Acquisition, analysis, or interpretation of data: Jatin Kadam, Amol..
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