{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T10:46:30Z","timestamp":1772793990485,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,5,22]],"date-time":"2018-05-22T00:00:00Z","timestamp":1526947200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100006259","name":"Teva Pharmaceutical Industries","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006259","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In this randomized double\u2010blind study, 4 groups of healthy subjects (50 per arm) participated to evaluate the effect of laquinimod, an oral treatment in development for multiple sclerosis and Huntington disease, on the QTc interval. Subjects received a dose of either 0.6 or 1.2\u00a0mg\/day laquinimod for 14 days, placebo for 14 days, or 13 days of placebo followed by a dose of 400\u00a0mg moxifloxacin on day\u00a014. Continuous 12\u2010lead electrocardiograms were recorded on day\u00a0\u20131 (baseline) and days\u00a014 to 17,\u00a0 and quadruplicate electrocardiograms were extracted at predefined time points. The primary measure was time\u2010matched change from baseline in individual QTc (QTcI), and an analysis of variance was conducted on the placebo\u2010corrected change from baseline data (ddQTcI). Pharmacokinetic\u2010pharmacodynamic and safety assessments were included. Results showed that the upper limits of the 2\u2010sided 90%CI for ddQTcI for both laquinimod doses were below 10\u00a0millisconds at all time points, whereas lower limits for moxifloxacin were above 5\u00a0milliseconds. No notable changes in ECG parameters were observed. Pharmacokinetic\/pharmacodynamic analysis showed no positive correlation between laquinimod plasma levels and QTcI. In conclusion, laquinimod was not found to affect cardiac repolarization or to cause prolongation of QTcI at doses of 0.6 and 1.2\u00a0mg\/day.<\/jats:p>","DOI":"10.1002\/cpdd.442","type":"journal-article","created":{"date-parts":[[2018,5,22]],"date-time":"2018-05-22T14:55:01Z","timestamp":1527000901000},"page":"49-59","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Thorough QT\/QTc Study With Laquinimod, a Novel Immunomodulator in Development for Multiple Sclerosis and Huntington Disease"],"prefix":"10.1002","volume":"8","author":[{"given":"Ofer","family":"Spiegelstein","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics Teva Pharmaceutical Industries Ltd  Netanya Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorit","family":"Mimrod","sequence":"additional","affiliation":[{"name":"Project Leadership Teva Pharmaceutical Industries Ltd  Netanya Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Rabinovich","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics Teva Pharmaceutical Industries Ltd  Frazer PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eli","family":"Eyal","sequence":"additional","affiliation":[{"name":"Global Biostatistics Unit TEVA Pharmaceutical Industries Ltd  Netanya Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig","family":"Sprenger","sequence":"additional","affiliation":[{"name":"Novum  Fargo ND USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Elgart","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Pharmacometrics Teva Pharmaceutical Industries Ltd  Netanya Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emil","family":"Samara","sequence":"additional","affiliation":[{"name":"PharmaPolaris International  Davis CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel","family":"Morganroth","sequence":"additional","affiliation":[{"name":"eResearch Technology, Inc  Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,5,22]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.02.019"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.05.011"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033797"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt023"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2010.07.009"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2012.06.005"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.09.037"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1607843113"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1586\/ecp.12.12"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-0945-z"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.104.002238"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1104318"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-014-7264-4"},{"issue":"3","key":"e_1_2_10_15_1","first-page":"74","article-title":"CONCERTO: a placebo\u2010controlled trial of oral laquinimod in patients with relapsing\u2010remitting multiple sclerosis","volume":"23","author":"Comi G","year":"2017","journal-title":"Mult Scler J"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(98)77782-3"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(98)77782-3"},{"key":"e_1_2_10_18_1","unstructured":"FDA.Guidance for Industry E14 Clinical Evaluation of QT\/QTc Interval Prolongation and Proarrhythmic Potential for Non\u2010Antiarrhythmic Drugs2005.http:\/\/www.fda.gov\/downloads\/drugs\/guidancecomplianceregulatoryinformation\/guidances\/ucm073161.pdf. 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