{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T08:08:26Z","timestamp":1784016506835,"version":"3.55.0"},"reference-count":15,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,9,11]],"date-time":"2018-09-11T00:00:00Z","timestamp":1536624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Dova Pharmaceuticals, Durham, NC, USA"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Avatrombopag is an oral thrombopoietin receptor agonist that has been recently approved for treating thrombocytopenia in chronic liver disease patients needing invasive procedures. Clinical trials supporting this new treatment were guided by two double\u2010blind, dose\u2010rising, placebo\u2010controlled Phase 1 studies in healthy adults reported here that assessed safety, tolerability and pharmacokinetic profile of avatrombopag, and its effect on platelet counts. Subjects were randomised (2:1) in the single\u2010dose study (<jats:italic>N<\/jats:italic>\u00a0=\u00a063) to avatrombopag (1, 3, 10, 20, 50, 75 and 100\u00a0mg) or placebo, and in the multiple\u2010dose study (<jats:italic>N<\/jats:italic>\u00a0=\u00a029) to avatrombopag (3, 10 and 20\u00a0mg) or placebo daily for 14\u00a0days. There were no serious adverse events (AEs), dose\u2010limiting toxicities, deaths, AEs causing withdrawal, thromboses or liver function abnormalities. In both studies, avatrombopag peak concentration and exposure increased proportionally relative to dose; half\u2010life was 18\u201321\u00a0h and independent of dose, supporting once\u2010daily dosing. Effects on platelet counts depended on dose, concentration and treatment duration. Platelet count increases began 3\u20135\u00a0days post\u2010administration, with maximum changes of &gt;370\u00a0\u00d7\u00a010<jats:sup>9<\/jats:sup>\/l over baseline with 20\u00a0mg daily after 13\u201316\u00a0days. These data support continued development of avatrombopag for treatment of other thrombocytopenic conditions and provide important guidance for the haematologist in the use of this new thrombopoietin receptor agonist.<\/jats:p>","DOI":"10.1111\/bjh.15574","type":"journal-article","created":{"date-parts":[[2018,9,11]],"date-time":"2018-09-11T09:26:30Z","timestamp":1536657990000},"page":"466-478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Avatrombopag, an oral thrombopoietin receptor agonist: results of two double\u2010blind, dose\u2010rising, placebo\u2010controlled Phase 1 studies"],"prefix":"10.1111","volume":"183","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2084-8810","authenticated-orcid":false,"given":"David J.","family":"Kuter","sequence":"first","affiliation":[{"name":"Center for Hematology Massachusetts General Hospital Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee F.","family":"Allen","sequence":"additional","affiliation":[{"name":"Dova Pharmaceuticals Durham NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2010.09.072"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.10.012"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa073275"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-07-514398"},{"key":"e_1_2_8_6_1","first-page":"68","article-title":"Single and multiple oral doses of AKR\u2010501 (YM477) increase the platelet count in healthy volunteers","volume":"5","author":"Desjardins R.E.","year":"2007","journal-title":"The Journal Of Supportive Oncology"},{"key":"e_1_2_8_7_1","unstructured":"Food and Drug Administration. (2018)FDA approves new drug for patients with chronic liver disease who have low blood platelets and are undergoing a medical procedure May 2018. Available at:https:\/\/www.fda.gov\/newsevents\/newsroom\/pressannouncements\/ucm608320.htm"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2008.04.020"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2008.01198.x"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-11-057968"},{"key":"e_1_2_8_11_1","first-page":"17","article-title":"Avatrombopag, a novel oral thrombopoietin receptor agonist, demonstrates superiority to placebo for the treatment of chronic immune thrombocytopenic purpura in a phase 3, multicenter, randomized, double\u2010blind, placebo\u2010controlled trial","volume":"130","author":"Jurczak W.","year":"2017","journal-title":"Blood"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.349"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.07.007"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.05.025"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-04-748707"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.02.060"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbjh.15574","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.15574","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T18:26:52Z","timestamp":1694802412000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.15574"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,11]]},"references-count":15,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1111\/bjh.15574"],"URL":"https:\/\/doi.org\/10.1111\/bjh.15574","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,11]]},"assertion":[{"value":"2018-04-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}