{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T17:54:26Z","timestamp":1759341266536},"reference-count":19,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2013,10,1]],"date-time":"2013-10-01T00:00:00Z","timestamp":1380585600000},"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":[[2013,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            GSK2336805 is an orally bioavailable hepatitis C virus (HCV) inhibitor working through an NS5A-mediated mechanism. This first-time-in-human study was conducted to assess the safety, tolerability, pharmacokinetics, metabolism, and efficacy of GSK2336805 in healthy subjects and subjects infected with HCV genotype 1. We performed a three-part, randomized, double-blind, placebo-controlled study in 46 healthy subjects and 23 HCV-infected subjects. After an overnight fast, healthy subjects received GSK2336805 as 10 mg, 30 mg, 30 mg plus food, and 60 mg in a single dose and 10 mg (7 days), 30 mg (7 days), and 75 mg (14 days) in a once-daily multiple dose. Subjects with HCV received GSK2336805 as a 1- to 120-mg single dose. In subjects with HCV, reductions in HCV RNA were observed within 4 h and a single dose of GSK2336805 of \u226510 mg resulted in a statistically significant \u22652-log reduction in HCV RNA compared with placebo at 24 h postdose. GSK2336805 was readily absorbed in all subjects, and the half-life (\n            <jats:italic>t<\/jats:italic>\n            <jats:sub>1\/2<\/jats:sub>\n            ) was suitable for once-daily dosing. Administration of GSK2336805 with food had no effect on plasma GSK2336805 exposure; however, absorption was delayed, with a median\n            <jats:italic>t<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            (time to maximum concentration of drug in serum) of 4.5 versus 2.0 h. Twenty subjects who received GSK2336805 experienced mild to moderate adverse events; none were serious. GSK2336805 was well tolerated and exhibited rapid, significant antiviral activity after a single dose in HCV-infected subjects. These results support the conduct of further studies evaluating GSK2336805 administered once daily for longer durations in combination with peginterferon, ribavirin, and other direct-acting antivirals. (This study has been registered at ClinicalTrials.gov under registration no. NCT01277692.)\n          <\/jats:p>","DOI":"10.1128\/aac.00910-13","type":"journal-article","created":{"date-parts":[[2013,7,30]],"date-time":"2013-07-30T02:10:10Z","timestamp":1375150210000},"page":"5037-5044","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of GSK2336805, an Inhibitor of Hepatitis C Virus (HCV) NS5A, in Healthy Subjects and Subjects Chronically Infected with HCV Genotype 1"],"prefix":"10.1128","volume":"57","author":[{"given":"D. A.","family":"Wilfret","sequence":"first","affiliation":[{"name":"GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Walker","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. K.","family":"Adkison","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. A.","family":"Jones","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y.","family":"Lou","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Gan","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Castellino","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline, Research Triangle Park, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. 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Approval of Incibek (telaprevir), a direct acting antiviral drug (DAA) to treat hepatitis C virus (HCV). US Food and Drug Administration, Silver Spring, MD. http:\/\/www.fda.gov\/ForConsumers\/ByAudience\/ForPatientAdvocates\/ucm256328.htm."},{"key":"e_1_3_3_9_2","volume-title":"Approval of Victrelis (boceprevir), a direct acting antiviral drug (DAA) to treat hepatitis C virus (HCV)","author":"US Food and Drug Administration","year":"2011","unstructured":"US Food and Drug Administration. 2011. Approval of Victrelis (boceprevir), a direct acting antiviral drug (DAA) to treat hepatitis C virus (HCV). US Food and Drug Administration, Silver Spring, MD. http:\/\/www.fda.gov\/ForConsumers\/ByAudience\/ForPatientAdvocates\/ucm255413.htm."},{"key":"e_1_3_3_10_2","volume-title":"Incivek (telaprevir) package insert","author":"Vertex Pharmaceuticals Inc.","year":"2011","unstructured":"Vertex Pharmaceuticals Inc. 2011. Incivek (telaprevir) package insert. 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Table for grading the severity of adult and pediatric adverse events, version 1.0. Division of Acquired Immunodeficiency Syndrome (DAIDS), National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD."},{"key":"e_1_3_3_18_2","first-page":"1004A","article-title":"Single-dose pharmacokinetics of daclatasvir (DCV; BMS-790052) in subjects with hepatic impairment compared with healthy subjects","volume":"54","author":"Bifano M","year":"2011","unstructured":"BifanoMSevinskyHPerssonAChungEWind-RotoloMHwangCNettlesRGraselaDMarbusyTDeMiccoMBertzR. 2011. Single-dose pharmacokinetics of daclatasvir (DCV; BMS-790052) in subjects with hepatic impairment compared with healthy subjects. Hepatology 54(Suppl S1):1004A.","journal-title":"Hepatology"},{"key":"e_1_3_3_19_2","volume-title":"46th Annu. Meet. Eur. 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Cambridge, MA."}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00910-13","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.00910-13","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T22:32:42Z","timestamp":1645482762000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.00910-13"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,10]]},"references-count":19,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2013,10]]}},"alternative-id":["10.1128\/AAC.00910-13"],"URL":"https:\/\/doi.org\/10.1128\/aac.00910-13","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,10]]},"assertion":[{"value":"2013-04-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-07-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-09-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}