{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T17:50:19Z","timestamp":1760550619502},"reference-count":17,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,7,31]],"date-time":"2018-07-31T00:00:00Z","timestamp":1532995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The treatment of hepatitis C virus (HCV) infection has been revolutionized by the development of all\u2010oral combination regimens of direct\u2010acting antiviral agents. The current analysis characterized the relationship between exposures of daclatasvir (DCV; tablets) and asunaprevir (ASV; capsules) and sustained virologic response (SVR) in Japanese patients who are HCV genotype (GT) 1b nonresponders to pegylated interferon (IFN) \u03b1\/ribavirin or IFN\u03b2\/ribavirin, and IFN\u2010based therapy\u2013ineligible naive\/intolerant patients receiving DCV and ASV, and provided insight into patient covariates that were most closely associated with efficacy. The relationship between the probability of achieving SVR at 12 weeks after treatment (SVR12) and average steady\u2010state plasma concentrations estimated from population pharmacokinetic models for DCV and ASV is described using a logistic regression model with data from a phase 2 and a phase 3 study in Japanese patients infected with HCV GT 1b (N=265). The functional form characterization, which describes a relationship between DCV and ASV average steady\u2010state plasma concentrations and SVR12, as well as covariate identification (demographic, laboratory, and prognostic and treatment covariates) were investigated during model development. The presence of the signature nonstructural protein 5A Y93H mutation at baseline was the only significant parameter of SVR12 in the final exposure\u2010response model. Model evaluation plots demonstrate that the final model was able to predict the observed SVR rates. Exposure\u2010response analysis supports the clinical utility of the combination regimen of 60\u2010mg once\u2010daily DCV and 100\u2010mg twice\u2010daily ASV in Japanese patients infected with HCV GT 1b.<\/jats:p>","DOI":"10.1002\/jcph.1262","type":"journal-article","created":{"date-parts":[[2018,8,1]],"date-time":"2018-08-01T11:59:49Z","timestamp":1533124789000},"page":"1479-1488","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exposure\u2010Response (Efficacy) Analysis of Daclatasvir and Asunaprevir in Japanese Patients With Hepatitis C Virus Infection"],"prefix":"10.1002","volume":"58","author":[{"given":"Takayo","family":"Ueno","sequence":"first","affiliation":[{"name":"Bristol\u2010Myers Squibb K.K.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayu","family":"Osawa","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb K.K.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuhiko","family":"Imai","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb K.K.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb K.K.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tushar","family":"Garimella","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb  NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,7,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2014.04.013"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-052915-015720"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000205"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2013.06.014"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01186-12"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.11.012"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13073"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27113"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.10.019"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61059-X"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.09.037"},{"key":"e_1_2_9_13_1","doi-asserted-by":"crossref","unstructured":"WeiL ShangMX XuM et. al.Daclatasvir and asunaprevir in non\u2010Japanese Asian patients with chronic HCV genotype 1b infection who are ineligible for or intolerant to interferon\u2010alfa therapies with or without ribavirin: phase 3 SVR12 interim results. The AASLD Liver Meeting. San Francisco;2015.","DOI":"10.1111\/jgh.13379"},{"key":"e_1_2_9_14_1","unstructured":"EleyT ChanP SverdlovO et\u00a0al.Improved bioavailability and mitigated food effect for asunaprevir utilizing a lipid\u2010based formulation: similar exposure with 100 mg twice\u2010daily soft\u2010gel capsule relative to 200 mg twice daily of phase 2 tablet. 52nd Interscience Conference Antimicrobial Agents Chemotherapy. San Francisco;2012."},{"key":"e_1_2_9_15_1","article-title":"Population pharmacokinetic analysis of daclatasvir and asunaprevir in Japanese subjects with hepatitis C virus infection","author":"Osawa M","journal-title":"J Clin Pharmacol"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1176344136"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0187409"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00556-10"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcph.1262","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1262","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T05:38:13Z","timestamp":1694410693000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.1262"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,31]]},"references-count":17,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1002\/jcph.1262"],"URL":"https:\/\/doi.org\/10.1002\/jcph.1262","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,31]]},"assertion":[{"value":"2018-01-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}