{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T13:56:05Z","timestamp":1791035765521,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>This study assessed the effect of cladribine tablets (CladT) on the pharmacokinetics (PK) of a combined oral contraceptive (COC) in pre\u2010menopausal women with relapsing multiple sclerosis. It was a randomized, double\u2010blind, two\u2010period, two\u2010sequence crossover study to assess steady\u2010state plasma PK (area under the concentration\u2013time curve and peak concentration) of COC (ethinylestradiol [EE] 30\u2009\u03bcg and levonorgestrel [LNG] 150\u2009\u03bcg) when co\u2010administered with CladT or placebo. Participants received 2\u2009weeks of active CladT treatment per course (Weeks 1 and 5 per year) to have a cumulative dose of 3.5\u2009mg\/kg over 2\u2009years as per label. Of the 24 randomized participants, 23 completed the study. The results showed that the concentration\u2013time profiles as well as PK parameters of EE and LNG in the plasma were similar when co\u2010administered with CladT or placebo. Analysis of variance confirmed the bioequivalence of EE and LNG in COC when co\u2010administered with either CladT or placebo. All participants were adequately exposed to cladribine. Repeat\u2010dose administration of CladT had no apparent effect on serum luteinizing hormone, follicle\u2010stimulating hormone, progesterone, or sex hormone\u2010binding globulin concentrations during concomitant treatment with COC. Co\u2010administration with COC did not change the known safety and tolerability profile of CladT and did not alter the PK of EE or LNG in a COC during the study. Therefore, the concomitant use of CladT is not expected to decrease the efficacy of COCs containing EE and LNG.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial Registration:<\/jats:bold>\n                    EudraCT Number: 2018\u2010001015\u201070.\n                  <\/jats:p>","DOI":"10.1111\/cts.70204","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T19:55:03Z","timestamp":1743710103000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Cladribine Tablets on the Pharmacokinetics of a Combined Oral Contraceptive in Pre\u2010Menopausal Women With Relapsing Multiple Sclerosis"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1326-5943","authenticated-orcid":false,"given":"Robert","family":"Hermann","sequence":"first","affiliation":[{"name":"Clinical Research Appliance (Cr Appliance)  Gelnhausen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4467-9011","authenticated-orcid":false,"given":"Kerstin","family":"Hellwig","sequence":"additional","affiliation":[{"name":"Department of Neurology Katholisches Klinikum, Ruhr University Bochum  Bochum Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0996-1152","authenticated-orcid":false,"given":"Sumedh","family":"Gaikwad","sequence":"additional","affiliation":[{"name":"The Healthcare Business of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Galazka","sequence":"additional","affiliation":[{"name":"Ares Trading SA, Eysins, Switzerland, an affiliate of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afrim","family":"Bytyqi","sequence":"additional","affiliation":[{"name":"The Healthcare Business of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8629-553X","authenticated-orcid":false,"given":"Dominic","family":"Jack","sequence":"additional","affiliation":[{"name":"Merck Serono Ltd., Feltham, UK, an affiliate of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2682-4670","authenticated-orcid":false,"given":"Axel","family":"Krebs\u2010Brown","sequence":"additional","affiliation":[{"name":"The Healthcare Business of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Vetter","sequence":"additional","affiliation":[{"name":"The Healthcare Business of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7480-113X","authenticated-orcid":false,"given":"Axel","family":"Nolting","sequence":"additional","affiliation":[{"name":"The Healthcare Business of Merck KGaA  Darmstadt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4039-9813","authenticated-orcid":false,"given":"Karthik","family":"Venkatakrishnan","sequence":"additional","affiliation":[{"name":"EMD Serono  Billerica Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3825-7074","authenticated-orcid":false,"given":"Jennifer Q.","family":"Dong","sequence":"additional","affiliation":[{"name":"EMD Serono  Billerica Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,1]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(23)01473\u20103"},{"key":"e_1_2_13_3_1","volume-title":"Atlas of MS","author":"The Multiple Sclerosis International Federation","year":"2020"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.5935\/1518\u20100557.20210022"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/21556660.2020.1721507"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/13524585241228103"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2020.05.005"},{"key":"e_1_2_13_8_1","unstructured":"European Medicines Agency \u201cMavenclad 10 mg Tablets: Summary of Product Characteristics \u201d2022 https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/mavenclad\u2010epar\u2010product\u2010information_en.pdf."},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010018\u20100695\u20109"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2013.754012"},{"key":"e_1_2_13_11_1","volume-title":"MAVENCLAD\u00ae (Cladribine) Tablets. 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