Efficacy and Safety of LX9211 for Relief of Diabetic Peripheral Neuropathic Pain (RELIEF-DPN 1): Results of a Double-Blind, Randomized, Placebo-Controlled, Proof-of-Concept Study

Objective: To evaluate the efficacy of LX9211 in reducing pain related to diabetic peripheral neuropathy (DPN). Research Design and Methods: This double-blind, multicenter, proof-of-concept trial randomized (1:1:1) 319 individuals with diabetic peripheral neuropathic pain (DPNP) to LX9211 10 mg (n=106), LX9211 20 mg (n=106), or matching placebo (n=107), administered once daily for 6 weeks. DPNP was rated daily using an 11-point numerical rating scale. The primary endpoint was change from baseline to week 6 in the average daily pain score. The difference between each LX9211 dose group and placebo was evaluated by mixed model repeated measures analysis. Results: Low-dose LX9211 achieved the primary efficacy endpoint: -1.39 versus -0.72 points for placebo; LS mean (SE) difference: -0.67 (0.249), 95% CI: -1.16, -0.18, p=0.007; the high-dose LX9211 demonstrated improvement in pain severity versus placebo (-1.27 vs. -0.72 points, respectively), but the between-group difference did not reach the prespecified statistical significance (-0.55 (0.254), 95% CI: -1.06, -0.05, p=0.030). Treatment benefit was observed beginning at week 1 and maintained thereafter. LX9211 also demonstrated improvement in several patient-reported secondary outcomes. Most common adverse events were dizziness, nausea, and headache. More participants treated with LX9211 (20 mg: 28 [26.4%], 10 mg: 17 [16.0%]) than placebo (3 [2.8%]) discontinued study drug prematurely due to adverse events; serious adverse events were uncommon (2 [1.9%], 0, and 1 [0.9%], respectively). Conclusions: These preliminary findings of improvement in DPNP with LX9211 support further investigation in larger trials.