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The midazolam treatment arm received the sensitive CYP3A substrate midazolam on Day 1, followed by NBI\u20101065845 alone on Days 5\u201313; on Day 14, NBI\u20101065845 was administered with midazolam, then NBI\u20101065845 alone on Day 15. The oral contraceptive treatment arm received ethinyl estradiol\u2013levonorgestrel on Day 1, then NBI\u20101065845 alone on Days 5\u201313; on Day 14, NBI\u20101065845 was administered with ethinyl estradiol\u2013levonorgestrel, then NBI\u20101065845 alone on Days 15\u201317. Blood samples were collected for pharmacokinetic analyses. The midazolam treatment arm comprised 14 men and 4 women, of whom 16 completed the study. Sixteen of the 17 healthy women completed the oral contraceptive treatment arm. After multiple daily doses of NBI\u20101065845, the geometric mean ratios (GMRs) (90% confidence interval) for maximum observed concentration were: midazolam, 0.94 (0.79\u20131.13); ethinyl estradiol, 1.00 (0.87\u20131.15); and levonorgestrel, 0.99 (0.87\u20131.13). For area under the plasma concentration\u2013time curve (AUC) from time 0 to infinity, the GMRs were as follows: midazolam, 0.88 (0.78\u20130.98); and ethinyl estradiol, 1.01 (0.88\u20131.15). For levonorgestrel, the GMR for AUC from time 0 to the last quantifiable concentration was 0.87 (0.78\u20130.96). These findings indicate that NBI\u20101065845 is not a CYP3A inducer and support its administration with CYP3A substrates. NBI\u20101065845 was generally well tolerated, with no new safety signals observed after coadministration of midazolam, ethinyl estradiol, or levonorgestrel.<\/jats:p>","DOI":"10.1111\/cts.13791","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T12:18:30Z","timestamp":1714738710000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Effects of the selective <scp>AMPA<\/scp> modulator <scp>NBI<\/scp>\u20101065845 on the pharmacokinetics of midazolam or ethinyl estradiol\u2013levonorgestrel in healthy adults"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7705-9401","authenticated-orcid":false,"given":"Swan","family":"Lin","sequence":"first","affiliation":[{"name":"Neurocrine Biosciences, Inc  San\u00a0Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Ionescu","sequence":"additional","affiliation":[{"name":"Neurocrine Biosciences, Inc  San\u00a0Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Maynard\u2010Scott","sequence":"additional","affiliation":[{"name":"Neurocrine Biosciences, Inc  San\u00a0Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Neurocrine Biosciences, Inc  San\u00a0Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8638-2086","authenticated-orcid":false,"given":"David P.","family":"Walling","sequence":"additional","affiliation":[{"name":"CenExel \u2013 CNS  Garden Grove California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maura","family":"Furey","sequence":"additional","affiliation":[{"name":"Neurocrine Biosciences, Inc  San\u00a0Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8466-0994","authenticated-orcid":false,"given":"Jaskaran B.","family":"Singh","sequence":"additional","affiliation":[{"name":"Neurocrine Biosciences, Inc  San\u00a0Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.2006.163.11.1905"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/da.20505"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2022.109308"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2021.07.027"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2019.1189"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2019.19020172"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2021.173289"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpsy.2013.10.005"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2013.87"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2020.20081251"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(17)30272-9"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-93888-0"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-02148-w"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01451-2"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-018-0266-7"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0279640"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1288"},{"key":"e_1_2_12_19_1","unstructured":"US Food and Drug Administration.Clinical drug interaction studies\u2014cytochrome P450 enzyme\u2010 and transporter\u2010mediated drug interactions. Accessed November 10 2022.https:\/\/www.fda.gov\/media\/134581\/download2022."}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.13791","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T11:25:44Z","timestamp":1716895544000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.13791"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5]]},"references-count":18,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1111\/cts.13791"],"URL":"https:\/\/doi.org\/10.1111\/cts.13791","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5]]},"assertion":[{"value":"2023-11-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13791"}}