{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T13:55:54Z","timestamp":1791035754983,"version":"4.1.0"},"reference-count":18,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:00:00Z","timestamp":1744070400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Aficamten is a next\u2010in\u2010class, small\u2010molecule, cardiac myosin inhibitor in development for treating hypertrophic cardiomyopathy (HCM). This 2\u2010part study evaluated aficamten's impact on QTc interval in healthy participants. Part A (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910) was an open\u2010label study to find the appropriate dose for thorough QT (TQT) evaluation in Part B. Part B (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200934) was a double\u2010blind, 3\u2010way crossover TQT study conducted as per ICH E14 guidance using negative (placebo) and positive (moxifloxacin) controls. A single 50\u2009mg aficamten dose achieved exposures (C\n                    <jats:sub>max<\/jats:sub>\n                    range: 124\u20131660\u2009ng\/mL) comparable to the highest clinical dose (20\u2009mg QD) in obstructive HCM patients (NCT05186818; [C\n                    <jats:sub>max<\/jats:sub>\n                    range: 131\u20131230\u2009ng\/mL]) and was chosen for TQT evaluation. Using concentration\u2010QT (C\u2010QT) modeling, the placebo\u2010 and baseline\u2010corrected QT interval using Fridericia's correction (\u0394\u0394QTcF) was \u22121.82\u2009msec (90% CI: \u22123.43, \u22120.214) at peak aficamten concentrations (298.3\u2009ng\/mL) following the 50\u2009mg dose. The 90% CI upper bound of \u0394\u0394QTcF for aficamten was &lt;\u200910\u2009msec at all post\u2010dose time points. Assay sensitivity was established by the 90% CI lower bound for moxifloxacin (\u0394\u0394QTcF) exceeding 5\u2009msec. Aficamten did not cause QTc prolongation (using C\u2010QT and by time point analyses) within observed plasma concentrations up to 1660\u2009ng\/mL (aficamten), 213\u2009ng\/mL (metabolite CK\u20103834282), and 343\u2009ng\/mL (metabolite CK\u20103834283). No clinically meaningful effect on electrocardiogram parameters, including absolute QTcF (\u2264\u2009450\u2009msec) and change from baseline in QTcF (\u2264\u200930\u2009msec) was noted in aficamten\u2010treated participants. Aficamten was generally well tolerated. In conclusion, there was no evidence of aficamten\u2010mediated QTc prolongation across the therapeutic concentration range in a formal TQT study.\n                  <\/jats:p>","DOI":"10.1111\/cts.70218","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T02:08:31Z","timestamp":1744164511000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinical Evaluation of the Effect of Aficamten on\n                    <scp>QT<\/scp>\n                    \/\n                    <scp>QTc<\/scp>\n                    Interval in Healthy Participants"],"prefix":"10.1111","volume":"18","author":[{"given":"Neha","family":"Maharao","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology Cytokinetics, Incorporated  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9678-0133","authenticated-orcid":false,"given":"Donghong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Cytokinetics, Incorporated  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyrell J.","family":"Simkins","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Cytokinetics, Incorporated  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen","family":"Bowles","sequence":"additional","affiliation":[{"name":"Department of Clinical Operations Cytokinetics, Incorporated  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genzhou","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics Cytokinetics, Incorporated  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youcef","family":"Benattia","sequence":"additional","affiliation":[{"name":"Department of Drug Safety and Pharmacovigilance Cytokinetics, Incorporated  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne","family":"Griffith","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Cytokinetics, Incorporated  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen B.","family":"Heitner","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Cytokinetics, Incorporated  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Kupfer","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Cytokinetics, Incorporated  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polina","family":"German","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Cytokinetics, Incorporated  South San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2401424"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c01290"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.70006"},{"key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s40262-025-01481-9","article-title":"Effect of Hepatic Impairment or Renal Impairment on the Pharmacokinetics of Aficamten","volume":"64","author":"Xu D.","year":"2025","journal-title":"Clinical Pharmacokinetics"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2024.2389407"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1227470"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2022.04.008"},{"key":"e_1_2_9_9_1","unstructured":"M. K.Pugsley E. T.Chin B. R.Winters et\u00a0al. \u201cCharacterization of Aficamten A Cardiac Myosin Inhibitor in Core Battery Safety Pharmacology Studies \u201d Presented at the Safety Pharmacology Society (SPS) Brussels Belgium September 18\u201021 2023."},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.10.020"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2023.07.003"},{"key":"e_1_2_9_12_1","unstructured":"US Food and Drug Administration \u201cGuidance for Industry: E14 Clinical Evaluation of QT\/QTc Interval Prolongation and Proarrhythmic Potential for Non\u2010Antiarrhythmic Drugs \u201d (2005) (Updated October 2005) accessed November 21 2005 https:\/\/www.fda.gov\/files\/drugs\/published\/E14\u2010Clinical\u2010Evaluation\u2010of\u2010QT\u2010QTc\u2010Interval\u2010Prolongation\u2010and\u2010Proarrhythmic\u2010Potential\u2010for\u2010Non\u2010Antiarrhythmic\u2010Drugs.pdf."},{"key":"e_1_2_9_13_1","unstructured":"US Food and Drug Administration \u201cGuidance for Industry: E14 Clinical Evaluation of QT\/QTc Interval Prolongation and Proarrhythmic Potential for Non\u2010Antiarrhythmic Drugs \u2014 Questions and Answers (R3). Docket Number: FDA\u20102004\u2010D\u20100241 \u201d (2017) (Last Update June 2017) Center for Drug Evaluation and Research & Center for Biologics Evaluation and Research accessed November 21 2024 https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/e14\u2010clinical\u2010evaluation\u2010qtqtc\u2010interval\u2010prolongation\u2010and\u2010proarrhythmic\u2010potential\u2010non\u2010antiarrhythmic\u20101."},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-017-9558-5"},{"key":"e_1_2_9_15_1","unstructured":"Bayer HealthCare Pharmaceuticals Inc \u201cAvelox\u00ae (Moxifloxacin Hydrochloride) Full Prescribing Information \u201d (1999) (Updated May 2019) accessed November 21 1999 https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/021085s065 021277s061lbl.pdf."},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270010378408"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3284"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr021"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2023.1112759"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70218","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.70218","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70218","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T13:40:50Z","timestamp":1791034850000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70218"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":18,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,4]]}},"alternative-id":["10.1111\/cts.70218"],"URL":"https:\/\/doi.org\/10.1111\/cts.70218","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"2024-12-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70218"}}