{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T10:18:07Z","timestamp":1791022687800,"version":"4.1.0"},"reference-count":19,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2012,12,1]],"date-time":"2012-12-01T00:00:00Z","timestamp":1354320000000},"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":[[2012,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            IDX184 is a liver-targeted prodrug of 2\u2032-methylguanosine (2\u2032-MeG) monophosphate. This study investigated the safety, tolerability, antiviral activity, and pharmacokinetics of IDX184 as a single agent in treatment-na\u00efve patients with genotype-1 chronic hepatitis C virus (HCV) infection. Forty-one patients with baseline HCV RNA \u2265 5 log\n            <jats:sub>10<\/jats:sub>\n            IU\/ml, alanine aminotransferase (ALT) \u2264 2.5\u00d7 the upper limit of normal, and compensated liver disease were dosed. Sequential cohorts of 10 patients, randomized 8:2 (active:placebo), received 25, 50, 75, and 100 mg of IDX184 once daily for 3 days, with a 14-day follow-up. There were no safety-related treatment discontinuations or serious adverse events. The adverse events and laboratory abnormalities observed for IDX184- and placebo-treated patients were similar. At the end of the 3-day treatment period, changes from baseline in HCV RNA levels (means \u00b1 standard deviations) were \u22120.5 \u00b1 0.6, \u22120.7 \u00b1 0.2, \u22120.6 \u00b1 0.3, and \u22120.7 \u00b1 0.5 log\n            <jats:sub>10<\/jats:sub>\n            for the 25-, 50-, 75-, and 100-mg doses, respectively, while viral load remained unchanged for the pooled placebo patients (\u22120.05 \u00b1 0.3 log\n            <jats:sub>10<\/jats:sub>\n            ). Patients with genotype-1a and patients with genotype-1b responded similarly. Serum ALT levels decreased, especially at daily doses \u2265 75 mg. During the posttreatment period, plasma viremia and serum aminotransferase levels returned to near pretreatment levels. No resistance mutations associated with IDX184 were detected. Plasma exposure of IDX184 and its nucleoside metabolite 2\u2032-MeG was dose related and low. Changes in plasma viral load correlated with plasma exposure of 2\u2032-MeG. In conclusion, the results from this proof-of-concept study show that small doses of the liver-targeted prodrug IDX184 were able to deliver significant antiviral activity and support further clinical evaluation of the drug candidate.\n          <\/jats:p>","DOI":"10.1128\/aac.01521-12","type":"journal-article","created":{"date-parts":[[2012,10,16]],"date-time":"2012-10-16T05:51:17Z","timestamp":1350366677000},"page":"6372-6378","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Short-Term Monotherapy with IDX184, a Liver-Targeted Nucleotide Polymerase Inhibitor, in Patients with Chronic Hepatitis C Virus Infection"],"prefix":"10.1128","volume":"56","author":[{"given":"Jacob","family":"Lalezari","sequence":"first","affiliation":[{"name":"Quest Clinical Research, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Asmuth","sequence":"additional","affiliation":[{"name":"Clinical and Translational Science Center, University of California Davis, Sacramento, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaldo","family":"Casir\u00f3","sequence":"additional","affiliation":[{"name":"Teodoro Alvarez Hospital, Buenos Aires, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Vargas","sequence":"additional","affiliation":[{"name":"Mayo Clinic Arizona, Phoenix, Arizona, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Quest Clinical Research, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Dubuc-Patrick","sequence":"additional","affiliation":[{"name":"Idenix Pharmaceuticals, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Chen","sequence":"additional","affiliation":[{"name":"Idenix Pharmaceuticals, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"McCarville","sequence":"additional","affiliation":[{"name":"Idenix Pharmaceuticals, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Pietropaolo","sequence":"additional","affiliation":[{"name":"Idenix Pharmaceuticals, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Jian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Idenix Pharmaceuticals, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Sullivan-B\u00f3lyai","sequence":"additional","affiliation":[{"name":"Idenix Pharmaceuticals, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Mayers","sequence":"additional","affiliation":[{"name":"Idenix Pharmaceuticals, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009482"},{"key":"e_1_3_2_3_2","doi-asserted-by":"crossref","first-page":"S220","DOI":"10.1016\/S0168-8278(08)60590-5","article-title":"In vitro antiviral activity and pharmacology of IDX184, a novel and potent inhibitor of HCV replication","volume":"48","author":"Cretton-Scott E","year":"2008","unstructured":"Cretton-ScottE. 2008. In vitro antiviral activity and pharmacology of IDX184, a novel and potent inhibitor of HCV replication. J. Hepatol. 48(Suppl 2):S220.","journal-title":"J. Hepatol."},{"key":"e_1_3_2_4_2","unstructured":"European Medicines Agency (EMEA). 2009. Guideline on the clinical evaluation of direct acting antiviral agents intended for treatment of chronic hepatitis C. European Medicines Agency London United Kingdom. http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Scientific_guideline\/2009\/09\/WC500003461.pdf."},{"key":"e_1_3_2_5_2","unstructured":"FDA. 2010. Chronic hepatitis C virus infection: developing direct-acting antiviral agents for treatment. 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Hepatol."},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06102-5"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01317-07"},{"key":"e_1_3_2_10_2","unstructured":"Merck & Co. Inc. 2011. Victrelis prescribing information. Merck & Co. Inc. 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