Selective Inhibition of NaV1.8 with VX-548 for Acute Pain.

Study Summary

274 patients experiencing moderate-to-severe acute pain following bunionectomy were randomized to receive high-dose VX-548, middle-dose VX-548, low-dose VX-548, hydrocodone bitartrate–acetaminophen, or placebo. The primary outcome of interest was the time-weighted sum of pain-intensity differences over 48 hours (SPID48), measured using the Numeric Pain Rating Scale (NPRS). Secondary outcomes included pain-intensity differences over 24 hours (SPID24), the proportion of patients achieving at least 30%, 50%, or 70% pain reduction, and adverse events. Outcomes were assessed over 48 hours. Overall, the results revealed that high-dose VX-548 provided greater pain relief than placebo, with a least-squares mean SPID48 difference of 36.8 (95% confidence interval [CI], 4.6 to 69.0). Lower doses did not demonstrate a clear analgesic benefit over placebo. These findings suggested that high-dose VX-548, a selective NaV1.8 inhibitor, could provide effective nonopioid pain relief following bunionectomy.