{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:45:50Z","timestamp":1778114750741,"version":"3.51.4"},"reference-count":31,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T00:00:00Z","timestamp":1668470400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Enanta Pharmaceuticals, Inc."}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antiviral Therapy"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic hepatitis B (CHB) remains a major cause of morbidity and mortality. EDP-514 is a potent core inhibitor of hepatitis B virus (HBV) that reduces viral load reduction in HBV-infected chimeric mice. This first-in-human study evaluated the safety, tolerability, and pharmacokinetics (PK) of EDP-514 in healthy subjects and antiviral activity in patients with CHB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In Part 1, 82 subjects received placebo or EDP-514 in fed or fasted state as single ascending doses of 50\u2013800\u00a0mg and multiple ascending doses of 200\u2013800\u00a0mg for 14 days. In Part 2, 24 HBV DNA-suppressed, nucleos(t)ide (NUC)-treated (i.e., NUC-suppressed) CHB patients received EDP-514 200\u2013800\u00a0mg or placebo for 28\u00a0days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      EDP-514 was well tolerated in healthy subjects and CHB patients with most adverse events of mild intensity. In Part 1, EDP-514 exposure increased in an approximately dose proportional manner up to 600\u00a0mg after single doses and up to 400\u00a0mg after 14-day dosing. In Part 2, EDP-514 exposure increased linearly with dose on Day 1 and Day 28, with some accumulation for Day 28 and median trough concentrations (C\n                      <jats:sub>trough<\/jats:sub>\n                      ) approximately 20-fold above the protein-adjusted 50% effective concentration (EC\n                      <jats:sub>50<\/jats:sub>\n                      ) for the dose range. Mean change in HBV RNA from baseline to Day 28 was \u22122.03, \u22121.67, \u22121.87, and \u22120.58 log U\/mL in the 200\u00a0mg, 400\u00a0mg, 800\u00a0mg, and placebo CHB groups, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>EDP-514 was well tolerated, had a PK profile supporting once daily dosing, and reduced HBV RNA levels in NUC-suppressed CHB patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13596535221127848","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T02:54:27Z","timestamp":1668567267000},"page":"135965352211278","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["EDP-514 in healthy subjects and nucleos(t)ide reverse transcriptase inhibitor-suppressed patients with chronic hepatitis B"],"prefix":"10.1177","volume":"27","author":[{"given":"Jordan J","family":"Feld","sequence":"first","affiliation":[{"name":"Toronto Centre for Liver Disease, University Health Network, Toronto, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Lawitz","sequence":"additional","affiliation":[{"name":"Texas Liver Institute, University of Texas Health San Antonio, San Antonio, TX, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuan","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology, San Diego, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Lalezari","sequence":"additional","affiliation":[{"name":"Quest Clinical Research, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tarek","family":"Hassanein","sequence":"additional","affiliation":[{"name":"Southern California Research Center, Coronado, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Martin","sequence":"additional","affiliation":[{"name":"Gastroenterology, University of Miami, Coral Gables, FL, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven-Huy","family":"Han","sequence":"additional","affiliation":[{"name":"University of California, Los Angeles, Los Angeles, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas","family":"Dieterich","sequence":"additional","affiliation":[{"name":"Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanne-Marie","family":"Giard","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Universitaire de Montr\u00e9al, Montr\u00e9al, QC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0416-1843","authenticated-orcid":false,"given":"Guy","family":"De La Rosa","sequence":"additional","affiliation":[{"name":"Enanta Pharmaceuticals, Inc., Watertown, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alaa","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Enanta Pharmaceuticals, Inc., Watertown, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ed","family":"Luo","sequence":"additional","affiliation":[{"name":"Enanta Pharmaceuticals, Inc., Watertown, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annie L","family":"Conery","sequence":"additional","affiliation":[{"name":"Enanta Pharmaceuticals, Inc., Watertown, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie","family":"Adda","sequence":"additional","affiliation":[{"name":"Enanta Pharmaceuticals, Inc., Watertown, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2022,11,15]]},"reference":[{"key":"bibr1-13596535221127848","doi-asserted-by":"publisher","DOI":"10.3390\/ph14050417"},{"key":"bibr2-13596535221127848","unstructured":"World Health Organization. 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