{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T02:52:15Z","timestamp":1785552735918,"version":"3.56.0"},"reference-count":28,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,1,21]],"date-time":"2019-01-21T00:00:00Z","timestamp":1548028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>The aim of this study was to characterize the effect of inotuzumab ozogamicin on QT interval in patients with B\u2010cell malignancies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data were pooled from three clinical studies including 250 patients (<jats:italic>n<\/jats:italic>\u00a0=\u00a02743) who received inotuzumab ozogamicin monotherapy. Patients with relapsed\/refractory acute lymphoblastic leukaemia (NCT01564784 and NCT01363297) received 1.8\u00a0mg\u00a0m<jats:sup>\u22122<\/jats:sup> per cycle in divided doses (mean <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> 371\u00a0ng\u00a0ml<jats:sup>\u22121<\/jats:sup>; considered therapeutic) and patients with relapsed\/refractory non\u2010Hodgkin lymphoma (NCT00868608) received 1.8\u00a0mg\u00a0m<jats:sup>\u22122<\/jats:sup> per cycle as a single dose (mean <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> 569\u00a0ng\u00a0ml<jats:sup>\u22121<\/jats:sup>; considered supratherapeutic). Triplicate 12\u2010lead electrocardiograms were performed at baseline and predefined time points postdose with paired pharmacokinetic collections. The exposure\u2013response relationship between corrected QT interval (QTc: QT interval corrected using population\u2010specific formula [QTcS] or QT interval corrected using Fridericia's formula [QTcF]) and inotuzumab ozogamicin concentration was characterized using a linear mixed\u2010effects model, and simulations were performed using the final validated model. Full model development involved testing for covariates that may account for part of the identified variability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>QTc intervals had a small but positive correlation with inotuzumab ozogamicin concentration. Based on 1000 simulations, median (upper 95% CI) QTcS and QTcF changes from baseline were &lt;10\u00a0ms at both therapeutic (2.70\u00a0ms [5.40\u00a0ms] and 2.53\u00a0ms [4.92\u00a0ms], respectively) and supratherapeutic (4.14\u00a0ms [8.28\u00a0ms] and 3.87\u00a0ms [7.54\u00a0ms], respectively) concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Inotuzumab ozogamicin (1.8\u00a0mg\u00a0m<jats:sup>\u22122<\/jats:sup> per cycle) is not predicted to pose a clinically significant safety risk for QT prolongation in patients with acute lymphoblastic leukaemia or non\u2010Hodgkin lymphoma.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.13832","type":"journal-article","created":{"date-parts":[[2018,12,8]],"date-time":"2018-12-08T09:49:10Z","timestamp":1544262550000},"page":"590-600","source":"Crossref","is-referenced-by-count":15,"title":["Effect of inotuzumab ozogamicin on the QT interval in patients with haematologic malignancies using QTc\u2010concentration modelling"],"prefix":"10.1111","volume":"85","author":[{"given":"Jennifer E.","family":"Hibma","sequence":"first","affiliation":[{"name":"Pfizer Oncology  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagop M.","family":"Kantarjian","sequence":"additional","affiliation":[{"name":"MD Anderson Cancer Center  Houston TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"DeAngelo","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology Dana\u2010Farber Cancer Institute  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph P.","family":"Boni","sequence":"additional","affiliation":[{"name":"Pfizer Oncology  Collegeville PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,1,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2014.10.021"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-0486"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20130067"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2014.09.014"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejh.12408"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.25410"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.1900"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2016001925"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14094"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509277"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2012.02241.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2488"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/21556660.2017.1315336"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2011.206"},{"key":"e_1_2_9_16_1","unstructured":"Pfizer.BESPONSA (inotuzumab ozogamicin). 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