{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T21:59:45Z","timestamp":1792879185089,"version":"4.5.0"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A combination of nucleotide hepatitis C virus (HCV) nonstructural protein (NS) 5B and 5A inhibitors is a preferred standard of care for treating chronic HCV. Bemnifosbuvir is a novel oral guanosine nucleotide prodrug with potent pan\u2010genotypic inhibitory activity against HCV NS5B. Ruzasvir, a small\u2010molecule NS5A inhibitor, has demonstrated improved anti\u2010HCV activity compared with first\u2010generation NS5A inhibitors. Clinical studies have demonstrated favorable efficacy and safety of bemnifosbuvir and ruzasvir in combination with other NS5A and NS5B inhibitors, respectively. A Phase 1 study in healthy participants was conducted to assess the drug\u2010drug interaction potential between bemnifosbuvir and ruzasvir, as well as food effects following coadministration of both compounds. Under fasted conditions, the peak, trough, and total exposure to bemnifosbuvir and its metabolites were increased upon coadministration with ruzasvir (by a maximum of 33% vs bemnifosbuvir alone), whereas the corresponding values for ruzasvir were decreased upon coadministration with bemnifosbuvir (by a maximum of 26% vs ruzasvir alone). Food delayed peak exposure to both drugs (by up to 2\u00a0hours) while increasing their peak and total exposure by up to 63%. No serious adverse events or premature drug discontinuations were reported. Overall, the study results support further evaluation of bemnifosbuvir and ruzasvir combination therapy for treating chronic HCV.<\/jats:p>","DOI":"10.1002\/cpdd.1540","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T14:38:46Z","timestamp":1745505526000},"page":"461-471","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Clinical Evaluation of Potential Interaction Between Bemnifosbuvir and Ruzasvir With an Assessment of Food Effect: Results of a Phase 1 Study in Healthy Participants"],"prefix":"10.1002","volume":"14","author":[{"given":"Xiao\u2010Jian","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Clinical Development at Atea Pharmaceuticals, Inc.  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Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.08.018"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(16)00635-8"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2024.2305137"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i20.3569"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11901-024-00655-6"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-052915-015720"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.14218\/JCTH.2020.00034"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2018.1472236"},{"key":"e_1_2_10_10_1","unstructured":"MungurO BerlibaE BourgeoisS et\u00a0al.A combination of AT\u2010527 a potent pan\u2010genotypic guanosine nucleotide prodrug and daclatasvir was well\u2010tolerated and effective in HCV\u2010infected subjects; Poster #THU438. Presented at:European Association for the Study of the Liver San Diego USA August 27\u201329.Elsevier;2020.https:\/\/ateapharma.com\/wp\u2010content\/uploads\/2020\/09\/90cmX140cm_Landscape_EASL2020_20200729_final.pdf."},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2021.05.008"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27726"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0227104"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02479-20"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01201-19"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.2217\/fvl-2023-0115"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28113-1"},{"key":"e_1_2_10_18_1","unstructured":"ZhouXJ RudoT HongqiXue et\u00a0al.A Phase 1 concentration\u2010QTc analysis shows bemnifosbuvir does not alter cardiac repolarization; Poster #PO419. Presented at:European Society of Clinical Microbiology and Infectious Diseases Barcelona Spain April 27\u201330.Wiley;2024.https:\/\/www.sciencedirect.com\/science\/article\/pii\/S2950590924000131\/pdfft?md5=cfbbad69290ae8ba19a2bf2aba56e548&pid=1\u2010s2.0\u2010S2950590924000131\u2010main.pdf."},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.13079"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01280-18"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofaa040"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo11020075"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/2050640616678151"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/hiv.12570"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.7861\/clinmedicine.13-5-511"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nutrit\/nuaa095"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12070672"},{"key":"e_1_2_10_28_1","unstructured":"GoodSS LinK LuoS VoA AgrawalN SommadossiJP.The combination of bemnifosbuvir (BEM) and ruzasvir (RZR) the HCV NS5B and NS5A inhibitors demonstrates potent in vitro synergistic antiviral activity and in vivo preclinical safety without adverse interactions. Poster #411. Presented at:6th International Conference on Antiviral Research (ICAR) Lyon France March 13\u201317.Elsevier;2023.https:\/\/ir.ateapharma.com\/static\u2010files\/d098a16b\u2010b837\u2010485e\u201086a0\u2010abd98e174908."},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.13132"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkae122"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00077-23"},{"key":"e_1_2_10_32_1","first-page":"S3","article-title":"Interpretation of dose\u2010dependent pharmacokinetics of ruzasvir using both physiologically Based Pharmacokinetic and population pharmacokinetic modeling approaches; Abstract M\u2010042","volume":"45","author":"Xia B","year":"2018","journal-title":"J Pharmacokinet Pharmacodyn"},{"key":"e_1_2_10_33_1","unstructured":"ZhouXJ DarpoB XueH MorelliG MontrondM PietropaoloK.Bemnifosbuvir does not alter cardiac repolarization in healthy participants: results from a thorough QT study; Poster #1466. 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