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. RESEARCH DESIGN AND METHODS In this double-blind, multicenter, proof-of-concept trial, 319 individuals with diabetic peripheral neuropathic pain (DPNP) were randomized (1:1:1) 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 with an 11-point numerical rating scale. The primary end point was change from baseline to week 6 in the average daily pain score. The difference between each LX9211 group and placebo was evaluated with mixed-model repeated-measures analysis. RESULTS For those on low-dose LX9211 the primary efficacy end point was achieved: −1.39 vs. −0.72 points for placebo, least squares mean (SE) difference −0.67 (0.249), 95% CI −1.16 to −0.18, P = 0.007; results for high-dose LX9211 demonstrated improvement in pain severity versus placebo (−1.27 vs. −0.72 points, respectively), but the between-group LS mean difference did not reach the prespecified statistical significance (−0.55 0.254, 95% CI −1.06 to −0.05, P = 0.030). Treatment benefit was observed beginning at week 1 and maintained thereafter. Results for LX9211 also demonstrated improvement in several patient-reported secondary outcomes. Most common adverse events (AEs) were dizziness, nausea, and headache. More participants treated with LX9211 (20 mg, n = 28 26.4%; 10 mg, 17 16.0%) than placebo (3 2.8%) discontinued study drug prematurely due to AEs; serious AEs 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.