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

Abstract

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.

Graphical abstract

Figure 1

LS mean difference in change from baseline in ADPS at week 6. ADPS was derived from participants’ answer to question no. 5 of the BPI-DPN (“Please rate your pain due to your diabetes by indicating the one number that best describes your pain on the average,” using an 11-point numerical rating scale [0 = no pain to 10 = pain as bad as you can imagine]). Baseline value was defined as the average of the week 2 run-in period data. A minimum of 4 days (consecutive or nonconsecutive) of daily pain diary data from week 5 to week 6 was required for the calculation of mean weekly ADPS at week 6.