{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T17:43:42Z","timestamp":1697046222395},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T00:00:00Z","timestamp":1545177600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/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":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The combination regimen of daclatasvir, asunaprevir, and beclabuvir has been developed for the treatment of hepatitis C virus infection. The objectives of this analysis were to characterize the relationship between the exposures of the daclatasvir, asunaprevir, and beclabuvir regimen and liver\u2010related laboratory elevations (Grade 3 or 4 alanine aminotransferase [ALT] and total bilirubin [Tbili]), and to evaluate the impact of selected covariates on the exposure\u2010response relationships. The exposure\u2010response analysis was performed with data from 1 phase 2 and 3 phase 3 studies in hepatitis C virus\u2013infected subjects. The probability of liver\u2010related laboratory elevations were modeled using linear logistic regression. Selected covariates were tested using a forward\u2010addition and backward\u2010elimination approach. The final model for ALT elevation included Asian race, body weight in non\u2010Asian subjects, and asunaprevir exposure. The final model for Tbili elevation included Asian race, fibrosis score (F0\u2010F3 or F4) and asupanprevir exposure. Asian subjects had greater the Grade 3 or 4 ALT and Tbili elevation rates than non\u2010Asians. The Grade 3 or 4 ALT elevation rate increased with decreasing body weight in non\u2010Asian subjects. Subjects with F4 fibrosis score had a higher rate of Grade 3 or 4 Tbili elevation compared to subjects with F0 to F3 fibrosis score. Higher asunaprevir exposure was associated with increases in Grade 3 or 4 ALT and Tbili elevation rates; however, the impact on the ALT elevation was not clinically relevant and the effect on Tbili elevation was smaller than the other significant covariates.<\/jats:p>","DOI":"10.1002\/jcph.1347","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T15:23:46Z","timestamp":1545233026000},"page":"557-565","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Safety Exposure\u2010Response Analysis for Daclatasvir, Asunaprevir, and Beclabuvir Combinations in HCV\u2010Infected Subjects"],"prefix":"10.1002","volume":"59","author":[{"given":"Mayu","family":"Osawa","sequence":"first","affiliation":[{"name":"Bristol\u2010Myers Squibb K.K.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayo","family":"Ueno","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb K.K.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomomi","family":"Shiozaki","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb K.K.  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanbin","family":"Li","sequence":"additional","affiliation":[{"name":"Certara  Menlo Park CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tushar","family":"Garimella","sequence":"additional","affiliation":[{"name":"Bristol\u2010Myers Squibb  Princeton NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,12,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26141"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.07.027"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000252782"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/he.2000.5762"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.09.001"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.02.006"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27113"},{"issue":"7","key":"e_1_2_8_9_1","first-page":"733","article-title":"Efficacy and safety of daclatasvir and asunaprevir combination therapy in chronic hemodialysis patients with chronic hepatitis C","volume":"51","author":"Suda G","year":"2016","journal-title":"Gastroenterol"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13379"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-015-0221-5"},{"key":"e_1_2_8_12_1","unstructured":"Eley TLW HuangS\u2010P HeB et\u00a0al.Evaluation of pharmacokinetic drug\u2010drug interactions (DDI) between BMS\u2010791325 an NS5b nonnucleoside polymerase inhibitor daclatasvir and asunaprevir in triple combination in hepatitis C virus (HCV) genotype 1\u2013infected patients.8th International Workshop on Clinical Pharmacology of Hepatitis Therapy.Cambridge MA;2013."},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.10.057"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2015.3868"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-016-1245-6"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.12964"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13796"},{"key":"e_1_2_8_18_1","unstructured":"ChanP ZhuL EleyT et al.Exposure\u2010safety analysis for asunaprevir and daclatasvir in DUAL combination in Japanese and non\u2010Japanese subjects with hepatitis C virus infection. Presented at: Asian Pacific Association for the Study of the Liver; March 12\u201315 2015; Istanbul."},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3851\/IMP2660"},{"key":"e_1_2_8_20_1","unstructured":"OsawaM UenoT ShiozakiT IshikawaH et\u00a0al.Population pharmacokinetic analysis of daclatasvir asunaprevir and beclabuvir in HCV\u2010infected non\u2010Japanese and Japanese subjects.World Conference of Pharmacometrics Brisbane Australia;2016."},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.361"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40261-017-0520-5"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-011-9255-z"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1274"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-018-0197-y"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcph.1347","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1347","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T18:51:09Z","timestamp":1694717469000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.1347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,19]]},"references-count":24,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1002\/jcph.1347"],"URL":"https:\/\/doi.org\/10.1002\/jcph.1347","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,19]]},"assertion":[{"value":"2018-08-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}