Vixotrigine is a voltage- and use-dependent Nav1.7 channel blocker under 
investigation for the treatment of peripheral neuropathic pain conditions, 
including trigeminal neuralgia. Vixotrigine is metabolized primarily via uridine 
diphosphate-glucuronosyltransferases (UGTs). Carbamazepine, a UGT and cytochrome 
P450 3A4 inducer, is a first-line treatment for trigeminal neuralgia. We 
conducted a double-blind, randomized, placebo-controlled, parallel-group, 
single-center 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 mg twice a day, days 1-3 and 200 mg 
twice a day, days 4-21) or placebo on days 1 to 21. All volunteers received 
vixotrigine 150 mg 3 times a day on days 16 to 28. At prespecified times, 
whole-blood samples were collected for PK assessment. Statistical analyses were 
performed on the log-transformed PK parameters area under the concentration-time 
curve within a dosing interval (AUC0-tau ) and maximum observed concentration 
(Cmax ) for vixotrigine, carbamazepine, and metabolites. Vixotrigine AUC0-tau 
and Cmax were reduced by 31.6% and 26.3%, respectively, when coadministered with 
carbamazepine compared with placebo. Seven days after carbamazepine 
discontinuation, vixotrigine AUC0-tau and Cmax remained 24.5% and 21.4% lower 
compared with placebo. Carbamazepine AUC0-tau and Cmax were <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.