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Subjects were randomly assigned to receive a single dose of trazodone 20\u00a0mg, 60\u00a0mg, and 140\u00a0mg, moxifloxacin 400\u00a0mg, and trazodone\u2010matched placebo in 5 periods separated by 7\u2010day washouts, according to a double\u2010blind, crossover study design. Subjects were monitored continuously, and triplicate ECGs were extracted from baseline (predose) until 24 hours postdose. Blood samples for trazodone and moxifloxacin analyses were collected at the same time points. The concentration\u2010QTc relationship assessed on placebo\u2010adjusted change from baseline for Fridericia\u2010corrected QT (\u0394\u0394QTcF) was the primary end point. \u0394\u0394QTcF values of 4.5, 12.3, and 19.8\u00a0ms for the 20\u2010, 60\u2010, and 140\u2010mg doses were observed at the corresponding trazodone peak plasma concentrations. The upper bound of the 90%CI exceeded 10\u00a0ms for the 60\u2010 and the 140\u2010mg doses. Time\u2010matched analysis results were in line with these findings. No significant trazodone effect on heart rate or PR or QRS intervals and no clinically significant new morphological changes were present. In this moxifloxacin\u2010validated ECG trial, trazodone had a modest, dose\u2010dependent effect on cardiac repolarization, with no QTc prolongation observed with the 20\u2010mg dose and an effect exceeding the values set in E14 guideline with the 60\u2010 and 140\u2010mg doses. The effect on cardiac repolarization is unlikely to represent a clinical risk for ventricular proarrhythmia, but caution should be used with concomitant use of other medications that prolong QT or increase trazodone exposure.<\/jats:p>","DOI":"10.1002\/jcph.1640","type":"journal-article","created":{"date-parts":[[2020,6,3]],"date-time":"2020-06-03T05:25:28Z","timestamp":1591161928000},"page":"1483-1495","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Effect of 3 Single Doses of Trazodone on QTc Interval in Healthy Subjects"],"prefix":"10.1002","volume":"60","author":[{"given":"Valeria","family":"Tellone","sequence":"first","affiliation":[{"name":"Angelini SpA Piazzale della Stazione  Pomezia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Rosignoli","sequence":"additional","affiliation":[{"name":"Angelini SpA Piazzale della Stazione  Pomezia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Picollo","sequence":"additional","affiliation":[{"name":"Angelini SpA Piazzale della Stazione  Pomezia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Dragone","sequence":"additional","affiliation":[{"name":"Angelini SpA Piazzale della Stazione  Pomezia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Del Vecchio","sequence":"additional","affiliation":[{"name":"Angelini SpA Piazzale della Stazione  Pomezia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Comandini","sequence":"additional","affiliation":[{"name":"Angelini SpA Piazzale della Stazione  Pomezia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milko","family":"Radicioni","sequence":"additional","affiliation":[{"name":"Cross Research SA  Arzo Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5594-6029","authenticated-orcid":false,"given":"Chiara","family":"Leuratti","sequence":"additional","affiliation":[{"name":"Cross Research SA  Arzo Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Calisti","sequence":"additional","affiliation":[{"name":"Angelini SpA Piazzale della Stazione  Pomezia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-012-0010-5"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.5.6.685"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1092852900024020"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002512-199404040-00006"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270009360979"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1993.tb01651.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00172631"},{"key":"e_1_2_10_9_1","unstructured":"Trazodone 75 and 150\u00a0mg Tablets.Summary of the product characteristics.https:\/\/www.medicines.org.uk\/emc\/product\/1744\/smpc. 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