{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T01:45:54Z","timestamp":1783129554408,"version":"3.54.6"},"reference-count":10,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T00:00:00Z","timestamp":1726531200000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A drug\u2013drug interaction (DDI) study was conducted to evaluate the effect of icenticaftor (QBW251) on the pharmacokinetics (PK) of a 5\u2010probe cytochrome P450 (CYP) substrate cocktail, guided by in\u00a0vitro studies in human hepatocytes and liver microsomes. Another DDI study investigated the effect of icenticaftor on the PK and pharmacodynamics (PD) of a monophasic oral contraceptive (OC) containing ethinyl estradiol (EE) and levonorgestrel (LVG) in premenopausal healthy female subjects. The static\u2010mechanistic DDI assessment indicated that icenticaftor may moderately induce the metabolic clearance of co\u2010medications metabolized by CYP3A4 (area under the concentration\u2013time curve [AUC] ratio: 0.47) and potentially CYP2C; icenticaftor may also weakly inhibit the metabolic clearance of co\u2010medications metabolized by CYP1A2 and CYP3A4 (AUC ratio: 1.35 and 1.86, respectively) and moderately inhibit CYP2B6 (AUC ratio: 2.11). In the CYP substrate cocktail DDI study, icenticaftor 300\u2009mg twice daily (b.i.d.) moderately inhibited CYP1A2 (AUC ratio: 3.35) and CYP2C19 (AUC ratio: 2.70). As expected from the results of the in\u00a0vitro studies, weak induction was observed for CYP3A4 (AUC ratio: 0.51) and CYP2C8 (AUC ratio: 0.66). In the OC DDI study, co\u2010administration of icenticaftor 450\u2009mg b.i.d. with monophasic OC containing 30\u2010\u03bcg EE and 150\u2010\u03bcg LVG once daily reduced the plasma exposure of both components by approximately 50% and led to increased levels of follicle\u2010stimulating hormone and luteinizing hormone. These results provide valuable guidance for the use of icenticaftor in patients taking concomitant medications that are substrates of CYP enzymes or patients using OCs.<\/jats:p>","DOI":"10.1111\/cts.70028","type":"journal-article","created":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T16:38:11Z","timestamp":1726591091000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Drug\u2013drug interactions of icenticaftor (QBW251) with a 5\u2010probe cytochrome P450 cocktail and oral contraceptives"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7121-4394","authenticated-orcid":false,"given":"Felix","family":"Huth","sequence":"first","affiliation":[{"name":"Novartis Pharma AG Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Glaenzel","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Drollmann","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Weis","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation East Hanover New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Zack","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation East Hanover New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidiya","family":"Bebrevska","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"2399","DOI":"10.2147\/COPD.S257474","article-title":"Efficacy and safety of the CFTR potentiator icenticaftor (QBW251) in COPD: results from a phase 2 randomized trial","volume":"15","author":"Rowe SM","year":"2020","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202303-0458OC"},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","unstructured":"GlaenzelU HuthF EggimannF et\u00a0al.Absorption distribution metabolism and excretion of icenticaftor (QBW251) in healthy male volunteers at steady state and in\u00a0vitro phenotyping of major metabolites. Drug Metab Disp 2024 accepted on 6th Sep 2024.","DOI":"10.1124\/dmd.124.001751"},{"key":"e_1_2_10_5_1","unstructured":"US Food and Drug Administration.Clinical drug interaction studies \u2014 cytochrome P450 enzyme\u2010 and transporter\u2010mediated drug interactions: guidance for industry.2020. Accessed October 2023.https:\/\/www.fda.gov\/media\/134581\/download"},{"key":"e_1_2_10_6_1","unstructured":"European Medicines Agency.Guideline on the investigation of drug interactions: CPMP\/EWP\/560\/95\/Rev. 1 Corr. 2.2012. Accessed October 2023.https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/guideline\u2010investigation\u2010drug\u2010interactions\u2010revision\u20101_en.pdf"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.105.013169"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.0306-5251.2003.01862.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.104.000182"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2690"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.119.089615"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70028","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T07:10:51Z","timestamp":1732777851000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70028"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9]]},"references-count":10,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1111\/cts.70028"],"URL":"https:\/\/doi.org\/10.1111\/cts.70028","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9]]},"assertion":[{"value":"2024-05-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70028"}}