{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T23:14:53Z","timestamp":1780096493329,"version":"3.54.0"},"reference-count":21,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T00:00:00Z","timestamp":1585094400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, USA"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The effects of supratherapeutic doses of intravenous (IV) relebactam on duration of ventricular depolarization and subsequent repolarization were assessed in a thorough QT\/corrected QT study. This was a single\u2010dose, double\u2010blind (relebactam only), randomized, placebo\u2010 and positive\u2010controlled, 3\u2010period, balanced crossover study in healthy participants. Participants received in randomized order, and separated by a washout (\u22654 days), a single dose of IV relebactam 1150 mg, oral moxifloxacin 400 mg (open\u2010label positive control), and IV placebo. Least squares mean and 2\u2010sided 90% confidence interval for change from baseline in population\u2010derived corrected QT intervals for relebactam, moxifloxacin, and placebo were estimated for 24 hours. The upper limit of the 90% confidence interval of all least squares mean population\u2010derived corrected QT treatment differences from placebo was not &gt;10 milliseconds at any time point for 24 hours. Corrected QT assay sensitivity was confirmed with moxifloxacin treatment. Analysis of electrocardiogram parameters resulted in no additional cardiac safety concerns. Overall, a supratherapeutic dose of relebactam yielded no cardiac safety events; the 1150\u2010mg supratherapeutic dose (4.6\u2010fold above the 250\u2010mg therapeutic dose) was not associated with QT prolongation or other abnormal cardiodynamic parameters. This study lends additional support to relebactam's use as a \u03b2\u2010lactamase inhibitor in antimicrobial therapy.<\/jats:p>","DOI":"10.1002\/cpdd.786","type":"journal-article","created":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T18:40:10Z","timestamp":1585161610000},"page":"466-475","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Thorough QTc Study of a Single Supratherapeutic Dose of Relebactam in Healthy Participants"],"prefix":"10.1002","volume":"9","author":[{"given":"Keith","family":"Boundy","sequence":"first","affiliation":[{"name":"Merck &amp; Co, Inc  Kenilworth New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"Merck &amp; Co, Inc  Kenilworth New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pratik","family":"Bhagunde","sequence":"additional","affiliation":[{"name":"Sanofi  Bridgewater New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry E.","family":"O'Reilly","sequence":"additional","affiliation":[{"name":"Celerion  Tempe Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francheska","family":"Colon\u2010Gonzalez","sequence":"additional","affiliation":[{"name":"Merck &amp; Co, Inc  Kenilworth New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan J.","family":"Friedman","sequence":"additional","affiliation":[{"name":"Abide Therapeutics  Princeton New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mallika","family":"Lala","sequence":"additional","affiliation":[{"name":"Merck &amp; Co, Inc  Kenilworth New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth G.","family":"Rhee","sequence":"additional","affiliation":[{"name":"Merck &amp; Co, Inc  Kenilworth New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew L.","family":"Rizk","sequence":"additional","affiliation":[{"name":"Merck &amp; Co, Inc  Kenilworth New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00826-13"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol202195n"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-017-0851-9"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.05927-11"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00830-15"},{"issue":"10","key":"e_1_2_10_7_1","first-page":"2286","article-title":"Activity of MK\u20107655 combined with imipenem against Enterobacteriaceae and Pseudomonas aeruginosa","volume":"68","author":"Livermore DM","year":"2013","journal-title":"J Antimicrob Chemother"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02209-16"},{"key":"e_1_2_10_9_1","article-title":"RESTORE\u2010IMI 1: a multicenter, randomized, double\u2010blind trial comparing efficacy and safety of imipenem\/relebactam vs colistin plus imipenem in patients with imipenem\u2010nonsusceptible bacterial infections [published online ahead of print August 10, 2019]","author":"Motsch J","journal-title":"Clin Infect Dis"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00633-16"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx139"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00280-18"},{"key":"e_1_2_10_13_1","unstructured":"US Food and Drug Administration. E14 clinical evaluation of QT\/QTc interval prolongation and proarrhythmic potential for non\u2010antiarrhythmic drugshttps:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16237860. Published2005. Accessed May 21 2019."},{"key":"e_1_2_10_14_1","unstructured":"ICH Expert Working Group.ICH Harmonised Tripartite Guideline. The clinical evaluation of QT\/QTc interval prolongation and proarrhythmic potential for non\u2010antiarrhythmic drugs. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.https:\/\/www.ema.europa.eu\/documents\/scientific-guideline\/ich-e-14-clinical-evaluation-qt\/qts-interval-prolongation-proarrhythmic-potential-non-antiarrhythmic-drugs-step-5_en.pdf. Published2005. Accessed July 10 2019."},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1086\/508873"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjp.2008.203"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1177\/1715163516641136"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928-017-9558-5"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.2307\/2533558"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.2174\/1574886311207040262"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.199"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl354"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpdd.786","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.786","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T02:33:25Z","timestamp":1694054005000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.786"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,25]]},"references-count":21,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1002\/cpdd.786"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.786","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,25]]},"assertion":[{"value":"2019-05-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}