{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:30:49Z","timestamp":1792449049414,"version":"4.5.0"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,11,27]],"date-time":"2022-11-27T00:00:00Z","timestamp":1669507200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In prior clinical studies, levocetirizine (LEVO) has demonstrated no effect on ventricular repolarization (QTc intervals), therefore it is a relevant negative control to assess in nonclinical assays to define low proarrhythmic risk. LEVO was tested in beagle dog and cynomolgus monkey (nonhuman primate [NHP]) telemetry models to understand the nonclinical\u2010clinical translation of this negative control. One oral dose of vehicle, LEVO (10\u00a0mg\/kg\/species) or moxifloxacin (MOXI; 30\u2009mg\/kg\/dog; 80\u2009mg\/kg\/NHP) was administered to instrumented animals (<jats:italic>N<\/jats:italic>\u00a0=\u00a08\/species) using a cross\u2010over dosing design; MOXI was the in\u2010study positive control. Corrected QT interval values (QTcI) were calculated using an individual animal correction factor. Blood samples were taken for drug exposure during telemetry and for pharmacokinetic (PK) analysis (same animals; different day) for exposure\u2010response (C\u2010QTc) modeling. Statistical analysis of QTc\u2010by\u2010timepoint data showed that LEVO treatment was consistent with vehicle, thus no effect on ventricular repolarization was observed over 24\u2009h in both species. PK analysis indicated that LEVO\u2010maximum concentration levels in dogs (range: 12,300\u201320,100\u2009ng\/ml) and NHPs (range: 4090\u201312,700\u2009ng\/ml) were \u22654\u2010fold higher than supratherapeutic drug levels in clinical QTc studies. Slope analysis values in dogs (0.00019\u2009ms\/ng\/ml) and NHPs (0.00016\u2009ms\/ng\/ml) were similar to the human C\u2010QTc relationship and indicated no relationship between QTc intervals and plasma levels of LEVO. MOXI treatment caused QTc interval prolongation (dog: 18\u2009ms; NHP: 29\u2009ms). The characterization of LEVO in these non\u2010rodent telemetry studies further demonstrates the value and impact of the in vivo QTc assay to define a \u201cno QTc effect\u201d profile and support clinical safety assessment.<\/jats:p>","DOI":"10.1111\/cts.13454","type":"journal-article","created":{"date-parts":[[2022,11,12]],"date-time":"2022-11-12T07:09:36Z","timestamp":1668236976000},"page":"436-446","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Evaluation of levocetirizine in beagle dog and cynomolgus monkey telemetry assays: Defining the no QTc effect profile by timepoint and concentration\u2010QTc analysis"],"prefix":"10.1111","volume":"16","author":[{"given":"Michael J.","family":"Engwall","sequence":"first","affiliation":[{"name":"Translational Safety &amp; Bioanalytical Sciences, Amgen Research  Thousand Oaks California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Baublits","sequence":"additional","affiliation":[{"name":"Translational Safety &amp; Bioanalytical Sciences, Amgen Research  Thousand Oaks California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona A.","family":"Chandra","sequence":"additional","affiliation":[{"name":"Amgen Clinical Pharmacology Modeling &amp; Simulation  Thousand Oaks California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zack W.","family":"Jones","sequence":"additional","affiliation":[{"name":"Amgen Clinical Pharmacology Modeling &amp; Simulation  Thousand Oaks California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Wahlstrom","sequence":"additional","affiliation":[{"name":"Pharmacokinetics Amgen Research  Thousand Oaks California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1162-8680","authenticated-orcid":false,"given":"Ray W.","family":"Chui","sequence":"additional","affiliation":[{"name":"Translational Safety &amp; Bioanalytical Sciences, Amgen Research  Thousand Oaks California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9447-3164","authenticated-orcid":false,"given":"Hugo M.","family":"Vargas","sequence":"additional","affiliation":[{"name":"Translational Safety &amp; 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