Mirogabalin for the treatment of diabetic peripheral neuropathic pain: A randomized, double-blind, placebo-controlled phase III study in Asian patients

Abstract

Aims/introduction: This study evaluated the efficacy and safety of mirogabalin, a novel, potent, selective ligand of the α₂ δ subunit of voltage-dependent Ca²⁺ channels, for the treatment of diabetic peripheral neuropathic pain (DPNP).

Materials and methods: During this double-blind, multisite, placebo-controlled phase III study, Asian patients aged ≥20 years with type 1 or 2 diabetes and DPNP were randomized 2:1:1:1 to a placebo, mirogabalin 15, 20 or 30 mg/day for up to 14 weeks, with a 1- to 2-week titration (NCT02318706). The primary endpoint was the change from baseline in average daily pain score (ADPS) at week 14, defined as a weekly average of daily pain (0 = no pain to 10 = worst possible pain, for the past 24 h).

Results: Of 834 randomized patients, 330, 164, 165 and 165 received placebo, mirogabalin 15, 20 or 30 mg/day, respectively, and were included in analyses (modified intention-to-treat population, n = 824); 755 (90.5%) completed the study. At week 14, the least squares mean average daily pain score change from baseline was -1.31, -1.34, -1.47 and -1.81, respectively, showing statistical significance for mirogabalin 30 mg/day versus placebo (P = 0.0027). The treatment-emergent adverse events observed were mostly mild-to-moderate in all mirogabalin doses, and the most frequent treatment-emergent adverse events were nasopharyngitis, somnolence, dizziness, peripheral edema and weight increase.

Conclusions: Mirogabalin relieved DPNP in a dose-dependent manner; mirogabalin 30 mg/day showed statistically significant pain relief (vs placebo) in Asian DPNP patients. All doses of mirogabalin tested were well tolerated.

Keywords: Diabetic peripheral neuropathic pain; Mirogabalin; Pain.

Figure 1

Patient disposition. ^a15 mg once daily. ^b10 mg twice daily. ^c15 mg twice daily. AE, adverse event; mITT, modified intention‐to‐treat (patients who were randomized and received 1 dose of study drug).

Figure 2

Average daily pain score shown as (a) the time course of the least squares mean ± standard error and (b) responder rates (≥30% and ≥50% improvement). ^a15 mg once daily. ^b10 mg twice daily. ^c15 mg twice daily. *P = 0.0048 compared with placebo. Data is presented for the modified intention‐to‐treat analysis set. The multiple imputation method was applied, using a pattern mixture model with different shift parameters depending on reasons for discontinuation (adverse event, lack of efficacy or others). The mixed effects model with repeated measures was carried out for the imputed datasets. This model included treatment, week and treatment‐by‐week as fixed effects; week as a repeated measure; and baseline ADPS as a covariate. Rubin's rule was used to provide the least squares means and its standard errors for each week of each treatment. ADPS, average daily pain score; BL, baseline.