{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T23:08:53Z","timestamp":1779923333090,"version":"3.53.1"},"reference-count":15,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,7,16]],"date-time":"2015-07-16T00:00:00Z","timestamp":1437004800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004374","name":"Medtronic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004374","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004337","name":"Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004337","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004315","name":"Human Genome Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004315","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004331","name":"Johnson and Johnson","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004331","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">GS<\/jats:styled-content>\u20105816 is an inhibitor of the hepatitis C virus (<jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>) <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>5A protein that has demonstrated pan\u2010genotypic activity and a high barrier to resistance in <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> replicon assays. The aim of this study was to evaluate the safety, antiviral activity and pharmacokinetics of once\u2010daily doses of <jats:styled-content style=\"fixed-case\">GS<\/jats:styled-content>\u20105816 in patients with genotype 1\u20134 <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> infection. Patients with genotype 1\u20134 <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> infection were randomized to 3\u00a0days of <jats:styled-content style=\"fixed-case\">GS<\/jats:styled-content>\u20105816 at doses ranging from 5 to 150\u00a0mg or placebo. Adverse events were recorded, and plasma samples obtained for analysis of pharmacokinetics, <jats:styled-content style=\"fixed-case\">HCV RNA<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>5A sequencing studies. <jats:styled-content style=\"fixed-case\">GS<\/jats:styled-content>\u20105816 5\u2013150\u00a0mg for 3\u00a0days was well tolerated and resulted in rapid declines in <jats:styled-content style=\"fixed-case\">HCV RNA<\/jats:styled-content> that were sustained over the dosing period. In patients treated with the 150\u00a0mg dose of <jats:styled-content style=\"fixed-case\">GS<\/jats:styled-content>\u20105816, the mean maximal <jats:styled-content style=\"fixed-case\">HCV RNA<\/jats:styled-content> declines were 4.0, 4.0, 4.4, 3.3 and 3.5 log<jats:sub>10<\/jats:sub> <jats:styled-content style=\"fixed-case\">IU<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content> in patients with genotype 1a, 1b, 2, 3 and 4 <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> infection, respectively. Pretreatment <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>5A resistance\u2010associated polymorphisms were detected in 31% (22\/70) of patients. Genotype 1 and 3 <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content>\u2010infected patients without pretreatment <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>5A resistance\u2010associated polymorphisms had greater declines in <jats:styled-content style=\"fixed-case\">HCV RNA<\/jats:styled-content> than patients with resistance\u2010associated polymorphisms. Plasma pharmacokinetics were supportive of once\u2010daily dosing. <jats:styled-content style=\"fixed-case\">GS<\/jats:styled-content>\u20105816 demonstrated pangenotypic antiviral activity in patients with genotype 1\u20104 <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> infection. It will be further evaluated in combination with other pangenotypic direct\u2010acting antivirals to achieve the goal of developing a well\u2010tolerated, highly effective treatment for all <jats:styled-content style=\"fixed-case\">HCV<\/jats:styled-content> genotypes.<\/jats:p>","DOI":"10.1111\/jvh.12435","type":"journal-article","created":{"date-parts":[[2015,7,16]],"date-time":"2015-07-16T11:48:49Z","timestamp":1437047329000},"page":"1011-1019","source":"Crossref","is-referenced-by-count":53,"title":["A phase 1, randomized, dose\u2010ranging study of <scp>GS<\/scp>\u20105816, a once\u2010daily <scp>NS<\/scp>5A inhibitor, in patients with genotype 1\u20134 hepatitis C virus"],"prefix":"10.1111","volume":"22","author":[{"given":"E.","family":"Lawitz","sequence":"first","affiliation":[{"name":"Texas Liver Institute University of Texas Health Sciences Center San Antonio TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Freilich","sequence":"additional","affiliation":[{"name":"Kansas City Gastroenterology and Hepatology Kansas City MO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Link","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc. Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"German","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc. Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Mo","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc. Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Han","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc. Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. M.","family":"Brainard","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc. Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"McNally","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc. Foster City CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Marbury","sequence":"additional","affiliation":[{"name":"Orlando Clinical Research Center Orlando FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Rodriguez\u2010Torres","sequence":"additional","affiliation":[{"name":"Fundacion De Investigacion San Juan Puerto Rico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,16]]},"reference":[{"key":"e_1_2_8_2_1","unstructured":"World Health Organization (WHO).Hepatitis C Fact sheet. Available at:http:\/\/www.who.int\/mediacentre\/factsheets\/fs164\/en\/#. 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