{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T14:03:05Z","timestamp":1782741785677,"version":"3.54.5"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,10,24]],"date-time":"2019-10-24T00:00:00Z","timestamp":1571875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Convergence Pharmaceuticals Ltd, a Biogen company"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Vixotrigine is a voltage\u2010 and use\u2010dependent Nav1.7 channel blocker under investigation for the treatment of peripheral neuropathic pain conditions, including trigeminal neuralgia. Vixotrigine is metabolized primarily via uridine diphosphate\u2010glucuronosyltransferases (UGTs). Carbamazepine, a UGT and cytochrome P450 3A4 inducer, is a first\u2010line treatment for trigeminal neuralgia. We conducted a double\u2010blind, randomized, placebo\u2010controlled, parallel\u2010group, single\u2010center phase 1 study to investigate the impact of coadministering vixotrigine and carbamazepine on their respective pharmacokinetics (PK) in healthy volunteers, the safety and tolerability of combined treatment, and PK recovery of vixotrigine following carbamazepine discontinuation. Randomly assigned treatments were carbamazepine (100\u00a0mg twice a day, days 1\u20103 and 200\u00a0mg twice a day, days 4\u201021) or placebo on days 1 to 21. All volunteers received vixotrigine 150\u00a0mg 3 times a day on days 16 to 28. At prespecified times, whole\u2010blood samples were collected for PK assessment. Statistical analyses were performed on the log\u2010transformed PK parameters area under the concentration\u2010time curve within a dosing interval (AUC<jats:sub>0\u2010tau<\/jats:sub>) and maximum observed concentration (C<jats:sub>max<\/jats:sub>) for vixotrigine, carbamazepine, and metabolites. Vixotrigine AUC<jats:sub>0\u2010tau<\/jats:sub> and C<jats:sub>max<\/jats:sub> were reduced by 31.6% and 26.3%, respectively, when coadministered with carbamazepine compared with placebo. Seven days after carbamazepine discontinuation, vixotrigine AUC<jats:sub>0\u2010tau<\/jats:sub> and C<jats:sub>max<\/jats:sub> remained 24.5% and 21.4% lower compared with placebo. Carbamazepine AUC<jats:sub>0\u2010tau<\/jats:sub> and C<jats:sub>max<\/jats:sub> were &lt;10% lower when coadministered with vixotrigine compared on days 15 and 21. Vixotrigine\/carbamazepine coadministration was well tolerated. These results suggest that vixotrigine does not have an effect on carbamazepine PK, and although carbamazepine has an effect on the exposure of vixotrigine, the effect is not considered clinically relevant.<\/jats:p>","DOI":"10.1002\/cpdd.739","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T04:54:53Z","timestamp":1571979293000},"page":"62-73","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Evaluation of the Pharmacokinetic Interaction Between the Voltage\u2010 and Use\u2010Dependent Nav1.7 Channel Blocker Vixotrigine and Carbamazepine in Healthy Volunteers"],"prefix":"10.1002","volume":"9","author":[{"given":"Joi","family":"Dunbar","sequence":"first","affiliation":[{"name":"Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Versavel","sequence":"additional","affiliation":[{"name":"Biogen  Cambridge Massachusetts USA"},{"name":"Convergence Pharmaceuticals a Biogen company  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Biogen  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Tate","sequence":"additional","affiliation":[{"name":"Convergence Pharmaceuticals a Biogen company  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Morisset","sequence":"additional","affiliation":[{"name":"Convergence Pharmaceuticals a Biogen company  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard M. 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