{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T23:19:38Z","timestamp":1780096778498,"version":"3.54.0"},"reference-count":21,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,5,2]],"date-time":"2021-05-02T00:00:00Z","timestamp":1619913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Durlobactam (formerly ETX2514) is a diazabicyclooctane \u03b2\u2010lactamase inhibitor that inhibits class A, C, and D \u03b2\u2010lactamases. Sulbactam combined with durlobactam has in vitro and in vivo activity against <jats:italic>Acinetobacter baumannii<\/jats:italic> including carbapenem\u2010 and colistin\u2010resistant isolates and is being developed for treating serious infections due to <jats:italic>A<\/jats:italic>.<jats:italic>\u00a0baumannii<\/jats:italic>. The effect of a single supratherapeutic dose of durlobactam on the heart rate corrected QT interval (QTc) was evaluated in healthy subjects in a placebo\u2010 and active\u2010controlled, single\u2010infusion, three\u2010way crossover study. Subjects were randomized to 1 of 6 sequences that included a single 3\u2010h i.v. infusion of durlobactam 4\u00a0g (supratherapeutic dose), a single 3\u2010h i.v. infusion of placebo, and a single 3\u2010h i.v. infusion of placebo plus a single oral dose of moxifloxacin 400\u00a0mg given open\u2010label at the end of the i.v. infusion. In each treatment period, Holter electrocardiogram (ECG) measurements were obtained from predose through 24 h post\u2010start of infusion. For the primary ECG end point, placebo\u2010corrected change\u2010from\u2010baseline corrected QT Fridericia\u2019s formula (\u0394\u0394QTcF), no significant change was observed with durlobactam. A concentration\u2010QT analysis demonstrated no significant effect of durlobactam on ECG parameters, including QT interval prolongation. Thus, durlobactam has a low risk for prolonging the QT interval and is unlikely to produce any proarrhythmic effects.<\/jats:p>","DOI":"10.1111\/cts.12991","type":"journal-article","created":{"date-parts":[[2021,5,2]],"date-time":"2021-05-02T08:22:10Z","timestamp":1619943730000},"page":"1423-1430","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A randomized, double\u2010blind, placebo\u2010 and positive\u2010controlled crossover study of the effects of durlobactam on cardiac repolarization in healthy subjects"],"prefix":"10.1111","volume":"14","author":[{"given":"John","family":"O\u2019Donnell","sequence":"first","affiliation":[{"name":"Entasis Therapeutics Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Maloney","sequence":"additional","affiliation":[{"name":"Johnson &amp; Johnson Spring House Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Steidler","sequence":"additional","affiliation":[{"name":"Entasis Therapeutics Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Royce","family":"Morrison","sequence":"additional","affiliation":[{"name":"Pharmaron Clinical Pharmacology Center Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Isaacs","sequence":"additional","affiliation":[{"name":"Entasis Therapeutics Waltham Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00159-19"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.7b00113"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmicrobiol.2017.104"},{"key":"e_1_2_9_5_1","unstructured":"McLeodSM MoussaS HackelM TommasiR MillerA.The novel beta\u2010lactamase inhibitor ETX2514 effectively restores sulbactam activity against recent global Acinetobacter baumannii\u2010calcoaceticus complex clinical isolates [abstract P1185]. In: Program and abstracts of the 29th European Congress of Clinical Microbiology and Infectious Diseases."},{"key":"e_1_2_9_6_1","unstructured":"McLeodSM RothB FlammR et al.2017The antibacterial activity of sulbactam and the novel beta\u2010lactamase inhibitor ETX2514 combined with imipenem or meropenem against recent clinical isolates ofAcinetobacter baumanniiandPseudomonas aeruginosa [abstract Friday\u201082]. In: Program and abstracts of ASM Microbe.Washington DC:American Society for Microbiology."},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01576-17"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa208"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00071-20"},{"issue":"9","key":"e_1_2_9_10_1","doi-asserted-by":"crossref","first-page":"e00794","DOI":"10.1128\/AAC.00794-19","article-title":"Pharmacokinetics, safety, and tolerability of intravenous ETX2514 and sulbactam in subjects with renal impairment and healthy matched control subjects","volume":"63","author":"O\u2019Donnell J","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01089-18"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01506-19"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp0706513"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/1755-5922.12054"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1086\/508873"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2165\/11531850-000000000-00000"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.34141"},{"key":"e_1_2_9_18_1","unstructured":"Food and Drug Administration: Center for Drug Evaluation and Research (CDER).Guidance for Industry: E14 Clinical Evaluation of QT\/QTc Interval Prolongation and Proarrhythmic Potential for Non Antiarrhythmic Drugs. Questions and Answers (R3)(June2017).https:\/\/www.fda.gov\/downloads\/Drugs\/GuidanceComplianceRegulatoryInformation\/Guidances\/UCM073161.pdf."},{"key":"e_1_2_9_19_1","volume-title":"E14 clinical evaluation of QT\/QTc interval prolongation and proarrhythmic potential for non\u2010anti\u2010arrhythmic drugs, October 2005","author":"International Conference on Harmonization","year":"2005"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-017-9558-5"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-015-0325-5"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/293564"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.12991","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.12991","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.12991","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T17:35:56Z","timestamp":1693330556000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.12991"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,2]]},"references-count":21,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1111\/cts.12991"],"URL":"https:\/\/doi.org\/10.1111\/cts.12991","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,2]]},"assertion":[{"value":"2020-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}