Novel Non-Opioid Shows Superior Pain Relief in Bunionectomy Trial
In a multicenter, randomized, double-blind, placebo-controlled phase 2b trial, researchers evaluated the efficacy and safety of XG005 in patients undergoing bunionectomy and found that the novel non-opioid analgesic yielded an improved reduction in summed pain intensity compared with placebo. These results were presented at the American Academy of Pain Medicine PainConnect 2025 annual meeting in Austin, TX.
The novel non-opioid, XG005, is a prodrug of pregabalin and naproxen designed to optimizing drug delivery by synchronizing Tmax and increasing Ctrough of both components, improving on traditional fixed-dose combinations.
For their study, the researchers enrolled 450 patients undergoing bunionectomy across eight US sites. Subjects were randomized 1:1:1 to receive either 1250 mg or 750 mg of XG005 or placebo twice daily, beginning 1 hour before surgery and continuing for 72 hours. Pain severity was assessed using the Numeric Pain Rating Scale (NPRS), and additional endpoints included use of rescue analgesia, sleep interference, and safety profiles.
The study’s primary endpoint, summed pain intensity over 48 hours (SPI48), showed that XG005 1250 mg resulted in a 53.6% improvement compared with placebo (P < .0001). The 750 mg dose yielded a 45.5% reduction in SPI48 versus placebo (P < .0001). Statistically significant pain reduction was observed in both treatment arms at all measured timepoints between 1 and 72 hours. The onset of pain relief occurred early, with superiority seen as early as 2 hours post-dose and sustained throughout the observation period.
The researchers noted that XG005 also reduced reliance on rescue medication. Median time to first use of tramadol was delayed eight-fold in the 1250 mg group and four-fold in the 750 mg group compared with placebo (P < .0001). Furthermore, total tramadol use during the first 48 hours was reduced by four-fold and three-fold, respectively, in the high- and low-dose XG005 groups.
“XG005 as a novel non-opioid analgesic has [an] effect size three-fold greater than opioids in acute pain,” the researchers concluded.
Reference
Jiang G-L, Evanson JR, Solanki D, et al. The efficacy and safety of XG005, a novel non-opioid analgesic, for acute pain: phase 2b trial. Presented at: PainConnect 2025, American Academy of Pain Medicine Annual Meeting; April 3-6, 2025; Austin, TX.