{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T12:43:24Z","timestamp":1767962604110,"version":"3.49.0"},"reference-count":25,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T00:00:00Z","timestamp":1401580800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2014,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            BMS-791325 is a nonnucleoside inhibitor of hepatitis C virus (HCV) NS5B polymerase with low-nanomolar potency against genotypes 1a (50% effective concentration [EC\n            <jats:sub>50<\/jats:sub>\n            ], 3 nM) and 1b (EC\n            <jats:sub>50<\/jats:sub>\n            , 7 nM)\n            <jats:italic>in vitro<\/jats:italic>\n            . BMS-791325 safety, pharmacokinetics, and antiviral activity were evaluated in a double-blind, placebo-controlled, single-ascending-dose study in 24 patients (interferon naive and experienced) with chronic HCV genotype 1 infection, randomized (5:1) to receive a single dose of BMS-791325 (100, 300, 600, or 900 mg) or placebo. The prevalence and phenotype of HCV variants at baseline and specific posttreatment time points were assessed. Antiviral activity was observed in all cohorts, with a mean HCV RNA decline of \u22482.5 log\n            <jats:sub>10<\/jats:sub>\n            copies\/ml observed 24 h after a single 300-mg dose. Mean plasma half-life among cohorts was 7 to 9 h; individual 24-hour levels exceeded the protein-adjusted EC\n            <jats:sub>90<\/jats:sub>\n            for genotype 1 at all doses. BMS-791325 was generally well tolerated, with no serious adverse events or discontinuations. Enrichment for resistance variants was not observed at 100 to 600 mg. At 900 mg, variants (P495L\/S) associated with BMS-791325 resistance\n            <jats:italic>in vitro<\/jats:italic>\n            were transiently observed in one patient, concurrent with an observed HCV RNA decline of 3.4 log\n            <jats:sub>10<\/jats:sub>\n            IU\/ml, but were replaced with wild type by 48 h. Single doses of BMS-791325 were well tolerated; demonstrated rapid, substantial, and exposure-related antiviral activity; displayed dose-related increases in exposure; and showed viral kinetic and pharmacokinetic profiles supportive of once- or twice-daily dosing. These results support its further development in combination with other direct-acting antivirals for HCV genotype 1 infection. (This trial has been registered at ClinicalTrials.gov under registration no. NCT00664625.)\n          <\/jats:p>","DOI":"10.1128\/aac.02579-13","type":"journal-article","created":{"date-parts":[[2014,4,15]],"date-time":"2014-04-15T03:30:53Z","timestamp":1397532653000},"page":"3496-3503","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Randomized, Placebo-Controlled, Single-Ascending-Dose Study of BMS-791325, a Hepatitis C Virus (HCV) NS5B Polymerase Inhibitor, in HCV Genotype 1 Infection"],"prefix":"10.1128","volume":"58","author":[{"given":"Karen D.","family":"Sims","sequence":"first","affiliation":[{"name":"Bristol-Myers Squibb Research and Development, Hopewell, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Lemm","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research and Development, Wallingford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Eley","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research and Development, Hopewell, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menping","family":"Liu","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research and Development, Wallingford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Berglind","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research and Development, Princeton, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane","family":"Sherman","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research and Development, Hopewell, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Lawitz","sequence":"additional","affiliation":[{"name":"The Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Apinya B.","family":"Vutikullird","sequence":"additional","affiliation":[{"name":"WCCT Global LLC, Cypress, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Tebas","sequence":"additional","affiliation":[{"name":"University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Gao","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research and Development, Wallingford, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Pasquinelli","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research and Development, Hopewell, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis M.","family":"Grasela","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb Research and Development, Hopewell, New Jersey, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2008.01934.x"},{"key":"e_1_3_2_3_2","volume-title":"Prevention and control of viral hepatitis infection: framework for global action","author":"World Health Organization","year":"2012","unstructured":"World Health Organization. 2012. 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