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Two drug\u2013drug interaction studies (NCT04008186 and NCT05909644) were performed to evaluate (1) the effect of drug\u2010metabolizing enzymes (DMEs) and drug transporter (DT) modulators on the pharmacokinetics of omaveloxolone and (2) the effect of omaveloxolone on the pharmacokinetics of DME and DT substrates. Additionally, the safety of coadministering these drugs with omaveloxolone was assessed. Coadministration of the strong CYP3A4 inhibitor itraconazole significantly increased omaveloxolone maximum plasma concentration (C<jats:sub>max<\/jats:sub>) and area under the plasma concentration\u2013time curve from time 0 extrapolated to infinity (AUC<jats:sub>0\u2010\u221e<\/jats:sub>) by approximately 3\u2010 and 4\u2010fold, respectively. Conversely, coadministration with the moderate CYP3A4 inducer efavirenz decreased C<jats:sub>max<\/jats:sub> and AUC<jats:sub>0\u2010\u221e<\/jats:sub> of omaveloxolone by 38.0% and 48.5%, respectively. Omaveloxolone exposure was also increased following coadministration with verapamil, a moderate CYP3A4 and P\u2010glycoprotein (P\u2010gp) inhibitor, but it was unaffected by the strong CYP2C8 inhibitor gemfibrozil. Coadministration of omaveloxolone reduced systemic exposure of the substrates of CYP3A4, CYP2C8, breast cancer resistance protein, and organic anion transporting polypeptide 1B1 but had no effect on those of P\u2010gp and organic cation transporter 1. Omaveloxolone was well tolerated when administered alone and in combination with the DME and DT modulators or substrates. These findings support concomitant medication precautions and dosing recommendations for omaveloxolone when coadministered with a moderate or strong CYP3A4 inhibitor or inducer, as well as the substrates of certain CYP450 enzymes\u00a0or transporters.<\/jats:p>","DOI":"10.1002\/jcph.6189","type":"journal-article","created":{"date-parts":[[2025,2,9]],"date-time":"2025-02-09T11:59:01Z","timestamp":1739102341000},"page":"715-730","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Clinical Assessment of the Drug\u2013Drug Interaction Potential of Omaveloxolone in Healthy Adult Participants"],"prefix":"10.1002","volume":"65","author":[{"given":"Hamim","family":"Zahir","sequence":"first","affiliation":[{"name":"Biogen, Inc.  Cambridge MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Murai","sequence":"additional","affiliation":[{"name":"Biogen, Inc.  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