{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:02Z","timestamp":1787013902877,"version":"build-2736575974"},"reference-count":27,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,5,6]],"date-time":"2019-05-06T00:00:00Z","timestamp":1557100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004755","name":"EMD Serono","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004755","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004755","name":"EMD Serono","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004755","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Cladribine tablets have shown significant efficacy for the treatment of relapsing multiple sclerosis, a chronic and debilitating immune\u2010mediated disorder. This study was conducted to examine acute and\/or cumulative effects of cladribine tablets 10\u00a0mg (3.5 or 5.25\u00a0mg\/kg cumulative dose over 2\u00a0years) on heart rate, AV conduction and cardiac repolarization in patients with relapsing\u2013remitting multiple sclerosis (RRMS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CLARITY was a 96\u2010week, double\u2010blind, placebo\u2010controlled, multicentre trial which evaluated the safety and efficacy of cladribine tablets 3.5 and 5.25\u00a0mg\/kg body weight in patients with RRMS. A total of 135 patients were included in the ECG substudy, providing a total of 1534 post\u2010dose ECGs. ECG data were collected 15\u00a0minutes pre\u2010dose and between 0.5 and 3\u00a0hours post\u2010dose at pre\u2010study evaluation, study Day 1 and Weeks 5, 9, 13, 48 and 52.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      For cladribine tablets 3.5\u00a0mg\/kg, the maximum change in placebo\u2010adjusted post\u2010dose QTcF\n                      <jats:italic>vs<\/jats:italic>\n                      . visit\u2010baseline (BL) was \u22120.42\u00a0ms (90% CI: \u22123.61\u20134.44) at Week 1 (acute effects), and 3.20\u00a0ms (90% CI: \u22120.08\u20136.33) for cladribine tablets 5.25\u00a0mg\/kg. The greatest observed differences in post\u2010dose QTcF\n                      <jats:italic>vs<\/jats:italic>\n                      . study BL occurred at Week 48 for both the 3.5 and 5.25\u00a0mg\/kg doses of cladribine tablets with 5.99\u00a0ms (90% CI: 0.53\u201311.44) and 8.74\u00a0ms (90% CI: 3.18\u201314.31), respectively. No significant changes were observed in T\u2010wave morphology in either treatment group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Cladribine tablets 3.5\u00a0mg\/kg (approved dose in Europe\/other regions) did not confer clinically meaningful effects on heart rate, AV conduction and ventricular repolarization.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.13919","type":"journal-article","created":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T20:08:02Z","timestamp":1552939682000},"page":"1484-1494","source":"Crossref","is-referenced-by-count":6,"title":["Effects of cladribine tablets on heart rate, atrio\u2010ventricular conduction and cardiac repolarization in patients with relapsing multiple sclerosis"],"prefix":"10.1111","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1326-5943","authenticated-orcid":false,"given":"Robert","family":"Hermann","sequence":"first","affiliation":[{"name":"cr\u2010appliance  Gelnhausen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S.","family":"Litwin","sequence":"additional","affiliation":[{"name":"WCG Clinical  Princeton NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena E.","family":"Friberg","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Dangond","sequence":"additional","affiliation":[{"name":"EMD Serono Inc.  Billerica MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain","family":"Munafo","sequence":"additional","affiliation":[{"name":"Quantitative Pharmacology Merck Institute for Pharmacometrics  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0902533"},{"key":"e_1_2_10_3_1","unstructured":"Merck Europe B.V.MAVENCLAD 10 mg tablets Summary of Product Characteristics;2018[online]. 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