{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:59:02Z","timestamp":1785430742313,"version":"3.56.0"},"reference-count":18,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T00:00:00Z","timestamp":1713830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Glecaprevir\/pibrentasvir (GLE\/PIB) is an approved guideline\u2010recommended chronic hepatitis C virus infection treatment. GLE\/PIB coadministration with ethinyl oestradiol (EE) is not recommended in current labels owing to a Phase 1 study observing Grade \u22652 alanine aminotransferase (ALT) elevation in 2 out of 12 healthy women cotreated for 11\u2009days with GLE\/PIB and oral contraceptive (OC) containing 35\u2009\u03bcg\/250\u2009\u03bcg EE\/norgestimate. No Grade \u22652 elevation was observed with low\u2010dose (20\u2009\u03bcg) EE (<jats:italic>n<\/jats:italic>\u2009=\u200914). This Phase 1 study examined safety\/tolerability of GLE\/PIB coadministered with an OC containing low\u2010dose EE using a larger sample size and longer treatment duration. Healthy premenopausal women were treated with EE\/levonorgestrel alone (20\/100\u2009\u03bcg, Cycles 1\u20132), followed by coadministration with GLE\/PIB (300\/120\u2009mg; Cycles 3\u20134). A safety criterion of special interest was a confirmed Grade \u22652 ALT elevation (&gt;3\u00d7 upper normal limit). Adverse events (AEs) and study drugs concentrations were examined. Of 85 enrolled women, 72 initiated combined GLE\/PIB\u2009+\u2009EE\/levonorgestrel treatment, 66 completed the study and 19 discontinued prematurely (non\u2010safety reason, <jats:italic>n<\/jats:italic>\u2009=\u200916; AE [deemed unelated to GLE\/PIB], <jats:italic>n<\/jats:italic>\u2009=\u20093). No participant met the safety criterion of special interest of confirmed Grade \u22652 ALT elevation. No serious\/Grade \u22653 AEs were reported. Study drug concentrations were within the expected ranges. GLE\/PIB in combination with an OC containing low\u2010dose EE was generally well tolerated with no confirmed Grade \u22652 ALT elevation and no evidence of drug\u2010induced liver injury. No pattern to the reported AEs and no new safety issues were identified. This was a Phase 1 study of healthy volunteers, not a registered clinical trial.<\/jats:p>","DOI":"10.1111\/jvh.13946","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T04:07:17Z","timestamp":1713931637000},"page":"409-415","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Phase 1 study of safety and tolerability of an oral contraceptive containing low\u2010dose ethinyl oestradiol combined with glecaprevir\/pibrentasvir treatment in healthy premenopausal women"],"prefix":"10.1111","volume":"31","author":[{"given":"Dee\u2010Dee","family":"Shiller","sequence":"first","affiliation":[{"name":"AbbVie, Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty B.","family":"Yao","sequence":"additional","affiliation":[{"name":"AbbVie, Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mong\u2010Jen","family":"Chen","sequence":"additional","affiliation":[{"name":"AbbVie, Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amelia","family":"Orejudos","sequence":"additional","affiliation":[{"name":"AbbVie, Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nael M.","family":"Mostafa","sequence":"additional","affiliation":[{"name":"AbbVie, Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Marcinak","sequence":"additional","affiliation":[{"name":"AbbVie, Inc.  North Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Burroughs","sequence":"additional","affiliation":[{"name":"AbbVie, Inc.  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Accessed August 10 2023"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(20)30359-9"},{"key":"e_1_2_9_6_1","volume-title":"Current Contraceptive Status among Women Aged 15\u201349: United States, 2015\u20132017: National Center for Health Statistics Data Brief","author":"Daniels K","year":"2018"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14011"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S172512"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/v13061048"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciad319"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.08.018"},{"key":"e_1_2_9_12_1","volume-title":"MAVYRET\u00ae (Glecaprevir\/Pibrentasvir). Full Prescribing Information","author":"AbbVie","year":"2021"},{"key":"e_1_2_9_13_1","unstructured":"Center for Drug Evaluation and Research (CDER).Application Number: 209394Orig1s000: Clinical Pharmacology and Biopharmaceuticals Review(s).2016Available from:https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2017\/209394orig1s000clinpharmr.pdfAccessed September 7 2023"},{"key":"e_1_2_9_14_1","volume-title":"Full Prescribing Information","author":"Teva Pharmaceuticals USA, Inc","year":"2022"},{"key":"e_1_2_9_15_1","unstructured":"US Department of Health & Human Services.Common terminology criteria for adverse events (CTCAE) Version 4.0.2010Available from:https:\/\/ctep.cancer.gov\/protocoldevelopment\/electronic_applications\/ctc.htm#ctc_40. 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