{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T03:16:46Z","timestamp":1768015006992,"version":"3.49.0"},"reference-count":22,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T00:00:00Z","timestamp":1548892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K23NS085049"],"award-info":[{"award-number":["K23NS085049"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR001117"],"award-info":[{"award-number":["UL1TR001117"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nitroxyl (HNO) is a reactive nitrogen molecule that has potential therapeutic benefits for patients with acute heart failure. The results of the first\u2010in\u2010human study for BMS\u2010986231, a novel HNO donor, are reported. The aim of this sequential cohort study was to evaluate the safety, tolerability, and pharmacokinetic profile of BMS\u2010986231 after 24\u2010 and 48\u2010hour intravenous infusions in healthy volunteers. Eighty subjects were randomized and dosed. Seven cohorts (stratum A) received BMS\u2010986231 0.1, 0.33, 1, 3, 5, 10, and 15\u00a0\u03bcg\/kg\/min or placebo, infused over 24\u00a0hours. An additional cohort (stratum B) received 10\u00a0\u03bcg\/kg\/min or placebo, infused over 48\u00a0hours. Adverse events (AEs) were reported for 30\u00a0days after completion of infusion. Blood\/urine samples were collected at regular intervals; other parameters (blood pressure, heart rate\/rhythm, cardiac index) were also assessed. Headaches were the most commonly reported drug\u2010related AE (48%) in those who received BMS\u2010986231, although their severity was reduced by hydration. No other significant drug\u2010related AEs were noted. BMS\u2010986231 was associated with dose\u2010dependent and well\u2010tolerated reductions in systolic and diastolic blood pressure versus baseline; cardiac index, as measured noninvasively, was increased. BMS\u2010986231 had no clinically significant effect on heart rate\/rhythm or laboratory parameters. Its mean elimination half\u2010life was 0.7\u20102.5\u00a0hours. BMS\u2010986231 was safe and well\u2010tolerated for up to 24 hours (15\u00a0\u03bcg\/kg\/min) or 48\u00a0hours (10\u00a0\u03bcg\/kg\/min), with a favorable hemodynamic profile observed. Ongoing studies continue to evaluate the potential benefit of BMS\u2010986231 in patients with acute heart failure.<\/jats:p>","DOI":"10.1002\/jcph.1364","type":"journal-article","created":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T17:39:41Z","timestamp":1548956381000},"page":"717-730","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A Phase 1 Randomized Study of Single Intravenous Infusions of the Novel Nitroxyl Donor BMS\u2010986231 in Healthy Volunteers"],"prefix":"10.1002","volume":"59","author":[{"given":"Douglas","family":"Cowart","sequence":"first","affiliation":[{"name":"Cardioxyl Pharmaceuticals, Inc.  Chapel Hill NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert P.","family":"Venuti","sequence":"additional","affiliation":[{"name":"Cardioxyl Pharmaceuticals, Inc.  Chapel Hill NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kim","family":"Lynch","sequence":"additional","affiliation":[{"name":"Duke Early Phase Clinical Research Unit  Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey T.","family":"Guptill","sequence":"additional","affiliation":[{"name":"Duke Early Phase Clinical Research Unit  Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert J.","family":"Noveck","sequence":"additional","affiliation":[{"name":"Duke Early Phase Clinical Research Unit  Durham NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi Yin","family":"Foo","sequence":"additional","affiliation":[{"name":"Cardioxyl Pharmaceuticals, Inc.  Chapel Hill NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,1,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2012.09.038"},{"issue":"4","key":"e_1_2_10_3_1","first-page":"e38","article-title":"Heart Disease and Stroke Statistics\u20102016 Update: a report from the American Heart Association","volume":"133","author":"Writing Group Members","year":"2016","journal-title":"Circulation"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1573403X09666131117174414"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.05.019"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-12-0130"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.592"},{"issue":"1","key":"e_1_2_10_8_1","first-page":"13","article-title":"Heart Failure Due to Reduced Ejection Fraction: Medical Management","volume":"95","author":"Chavey WE","year":"2017","journal-title":"Am Fam Physician"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000253904.53601.c9"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.108.188441"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi801925p"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.5057"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.2741\/e118"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000072010.54901.DE"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.113.000632"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11897-014-0210-z"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12568"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0937302100"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2018.07.003"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.270827"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.897"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.70.1164"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2648.2009.04980.x"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcph.1364","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1364","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.1364","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1364","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T06:09:47Z","timestamp":1694239787000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.1364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,31]]},"references-count":22,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,5]]}},"alternative-id":["10.1002\/jcph.1364"],"URL":"https:\/\/doi.org\/10.1002\/jcph.1364","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,31]]},"assertion":[{"value":"2018-06-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-01-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}