{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T22:28:41Z","timestamp":1770416921573,"version":"3.49.0"},"reference-count":21,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,11,19]],"date-time":"2018-11-19T00:00:00Z","timestamp":1542585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004326","name":"BAYER AG","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004326","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The chymase inhibitor fulacimstat is developed as a first\u2010in\u2010class treatment option for the inhibition of adverse cardiac remodeling in patients with left ventricular dysfunction (LVD) after acute myocardial infarction (MI). The aim of the study was to examine the safety and tolerability of fulacimstat in patients with LVD after remote MI. A multicenter, multinational randomized, placebo\u2010controlled study was performed in clinically stable patients (40\u201379 years of age, left ventricular ejection fraction \u2264 45% because of MI in medical history) who were on stable evidence\u2010based standard\u2010of\u2010care therapies for LVD post\u2010MI including an angiotensin converting enzyme inhibitor or angiotensin receptor blocker at doses of at least half the recommended target dose. Patients were treated for 2 weeks with either placebo (n\u00a0=\u00a012) or 4 different doses of fulacimstat (5\u00a0mg twice daily, n\u00a0=\u00a09; 10\u00a0mg twice daily, n\u00a0=\u00a09; 25\u00a0mg twice daily, n\u00a0=\u00a010; 50\u00a0mg once daily, n\u00a0=\u00a09). Fulacimstat was safe and well tolerated at all examined doses. There were no clinically relevant effects on vital signs or potassium levels compared with placebo treatment. Mean plasma concentrations of fulacimstat increased with the administered dose and reached exposures predicted to be therapeutically active. The safety profile and the absence of effects on blood pressure or heart rate in a chronic patient population having similar comorbidities and receiving similar comedication as patients after acute MI support future clinical trials with fulacimstat in patients after acute MI.<\/jats:p>","DOI":"10.1002\/cpdd.633","type":"journal-article","created":{"date-parts":[[2018,11,19]],"date-time":"2018-11-19T18:49:14Z","timestamp":1542653354000},"page":"942-951","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Safety and Tolerability of the Chymase Inhibitor Fulacimstat in Patients With Left Ventricular Dysfunction After Myocardial Infarction\u2014Results of the CHIARA MIA 1 Trial"],"prefix":"10.1002","volume":"8","author":[{"given":"Hans\u2010Dirk","family":"D\u00fcngen","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Cardiology Charit\u00e9\u2010Universitaetsmedizin  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Kober","sequence":"additional","affiliation":[{"name":"Department of Cardiology Copenhagen University Hospital Rigshospitalet  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Savina","family":"Nodari","sequence":"additional","affiliation":[{"name":"Cardiology Section Department of Clinical and Surgical Specialties Radiological Sciences and Public Health University of Brescia  Brescia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morten","family":"Schou","sequence":"additional","affiliation":[{"name":"Department of Cardiology Cardiovascular Research Center Gentofte and Herlev University Hospital  Herlev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christiane","family":"Otto","sequence":"additional","affiliation":[{"name":"Experimental Medicine Cardiovascular and Hematology BAYER AG  Wuppertal Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Becka","sequence":"additional","affiliation":[{"name":"Research and Clinical Sciences Statistics BAYER AG  Wuppertal Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friederike","family":"Kanefendt","sequence":"additional","affiliation":[{"name":"Clinical Pharmacokinetics BAYER AG  Wuppertal Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernhard R.","family":"Winkelmann","sequence":"additional","affiliation":[{"name":"ClinPhenomics GmbH &amp; Co KG  Frankfurt Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunnar","family":"Gislason","sequence":"additional","affiliation":[{"name":"Department of Cardiology Copenhagen University Hospital Herlev and Gentofte  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"Richard","sequence":"additional","affiliation":[{"name":"Private Praxis for Cardiology  Erfurt Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olav Wendelboe","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Copenhagen University Hospital Bispebjerg  Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihai","family":"Gheorghiade","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Innovation Northwestern University Feinberg School of Medicine  Chicago IL USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Senni","sequence":"additional","affiliation":[{"name":"Division of Cardiology 1 Papa Giovanni XXIII Hospital  Bergamo Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,11,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.030798"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2579832"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2017.09.015"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000036014.90197.FA"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2010.10.008"},{"key":"e_1_2_9_7_1","first-page":"1190","article-title":"Patterns of post\u2010MI left ventricular volume changes \u2013 clinical implications","volume":"65","author":"Brzezinska B","year":"2007","journal-title":"Kardiol Pol"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330-010-1963-8"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-12-0043"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2006.06.011"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/1440-1681.12549"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028501"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.310978"},{"key":"e_1_2_9_14_1","first-page":"A13624","article-title":"A novel chymase inhibitor BAY 1142524 reduces fibrosis and improves cardiac function after myocardial infarction in hamster","volume":"136","author":"Tinel H","year":"2017","journal-title":"Circulation"},{"key":"e_1_2_9_15_1","first-page":"A11585","article-title":"Long\u2010term therapy with a chymase inhibitor (BAY 1142524) improves left ventricular systolic function and prevents progressive chamber remodeling in dogs with heart failure","volume":"136","author":"Sabbah HN","year":"2017","journal-title":"Circulation"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.579"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.crd.0000195220.62533.c5"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejheart.2005.07.002"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.566"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1409077"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.115.002727"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2011.05.025"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpdd.633","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.633","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.633","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.633","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T17:27:22Z","timestamp":1694021242000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.633"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,19]]},"references-count":21,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["10.1002\/cpdd.633"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.633","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,19]]},"assertion":[{"value":"2018-09-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}