{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T10:07:13Z","timestamp":1756462033324},"reference-count":15,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T00:00:00Z","timestamp":1630368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bempedoic acid is an inhibitor of adenosine triphosphate\u2013citrate lyase approved for use in adults with hypercholesterolemia. Nonclinical studies assessed binding to the human ether\u2010a\u2010go\u2010go\u2013related gene (hERG) potassium channel in vitro and the effect of bempedoic acid on QT\/QTc in cynomolgus monkeys. A randomized, double\u2010blind, parallel\u2010design clinical study assessed the effects of steady\u2010state bempedoic acid at a supratherapeutic dose (240\u00a0mg\/day, 33.3% higher the180\u00a0mg\/day therapeutic dose), placebo, and moxifloxacin (400\u00a0mg) in healthy subjects. In vitro binding potency for bempedoic acid to the hERG potassium channel was weak, with half\u2010maximal inhibition (IC<jats:sub>50<\/jats:sub>) estimated at greater than 1000\u00a0\u03bcM (&gt;1670\u2010fold the bempedoic acid 180\u00a0mg\/day steady\u2010state unbound maximum concentration). In monkeys, individual rate\u2010corrected QT intervals showed no time\u2010 or dose\u2010dependent changes up to 100\u00a0mg\/kg of bempedoic acid. In human subjects, the upper 90% confidence interval (CI) for the difference in QTc interval, corrected using Fridericia\u2019s formula (QTcF), between bempedoic acid and placebo was less than 5\u00a0msec at all time points. Concentration\u2010QTcF analysis showed that maximum bempedoic acid concentration at steady\u2010state was attained at a median 2.1\u00a0h postdose, and the predicted mean change (90% CI) in QTcF at the observed mean bempedoic acid concentration 2\u00a0h postdose was \u22120.5 (\u22125.0, 4.0)\u00a0msec. The lower bound of the moxifloxacin 90% CI exceeded 5\u00a0msec at prespecified time points, establishing study sensitivity. Steady\u2010state bempedoic acid at a supratherapeutic dose of 240\u00a0mg was generally well\u2010tolerated and not associated with QTc prolongation in healthy subjects.<\/jats:p>","DOI":"10.1111\/cts.13116","type":"journal-article","created":{"date-parts":[[2021,8,31]],"date-time":"2021-08-31T07:19:35Z","timestamp":1630394375000},"page":"2487-2496","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Absence of effect of steady state bempedoic acid on cardiac repolarization: Results of a thorough QT\/QTc study in healthy volunteers"],"prefix":"10.1111","volume":"14","author":[{"given":"Benny M.","family":"Amore","sequence":"first","affiliation":[{"name":"Esperion Therapeutics, Inc. Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clay T.","family":"Cramer","sequence":"additional","affiliation":[{"name":"Nonclinical Pharma Solutions, LLC Dexter Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diane E.","family":"MacDougall","sequence":"additional","affiliation":[{"name":"Esperion Therapeutics, Inc. Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William J.","family":"Sasiela","sequence":"additional","affiliation":[{"name":"Esperion Therapeutics, Inc. Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurice G.","family":"Emery","sequence":"additional","affiliation":[{"name":"Esperion Therapeutics, Inc. Ann Arbor Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,8,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/2042098612454283"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2002.01627.x"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(02)00846-5"},{"key":"e_1_2_10_5_1","unstructured":"US Food and Drug Administration.Guidance for industry: S7B nonclinical evaluation of the potential for delayed ventricular repolarization (QT interval prolongation) by human pharmaceutical use;2005.https:\/\/www.fda.gov\/media\/72043\/download. Accessed July 29 2020."},{"key":"e_1_2_10_6_1","unstructured":"US Food and Drug AdministrationGuidance for Industry: E14 Clinical Evaluation of QT\/QTc Interval Prolongation and Proarrhythmic Potential for Non\u2010antiarrhythmic Drugs; 2005.https:\/\/www.fda.gov\/media\/71372\/download.Accessed July 29 2020."},{"key":"e_1_2_10_7_1","unstructured":"European Medicines Agency.ICH topic: E14 Clinical Evaluation of QT\/QTc Interval Prolongation and Proarrhythmic Potential for Non\u2010antiarrhythmic Drugs;2005.https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/ich\u2010e\u201014\u2010clinical\u2010evaluation\u2010qt\/qts\u2010interval\u2010prolongation\u2010proarrhythmic\u2010potential\u2010non\u2010antiarrhythmic\u2010drugs\u2010step\u20105_en.pdf. Accessed January 8 2021."},{"key":"e_1_2_10_8_1","volume-title":"Nexletol [prescribing information]","year":"2020"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2018.06.002"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.16585"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.118.011662"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1803917"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1538\/expanim.51.465"},{"key":"e_1_2_10_14_1","unstructured":"US Food and Drug Administration.211616Orig1s000 Integrated Review \u2212 Nexletol (bempedoic acid) Tablets;2020.https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2020\/211616Orig1s000IntegratedR.pdf. Accessed June 8 2021."},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-017-9558-5"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2020.08.009"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13116","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.13116","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T04:22:46Z","timestamp":1693196566000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.13116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,31]]},"references-count":15,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1111\/cts.13116"],"URL":"https:\/\/doi.org\/10.1111\/cts.13116","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,31]]},"assertion":[{"value":"2021-03-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-08-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}