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 α2δ 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.

Long‐term safety and efficacy of mirogabalin in Asian patients with diabetic peripheral neuropathic pain

“…It shows potent and long‐lasting analgesic effects in rat models for neuropathic pain and a wider safety margin for CNS side‐effects. In the preceding double‐blind phase III trial in Asian patients with DPNP, mirogabalin 15–30 mg/day was well tolerated and relieved DPNP in a dose‐dependent manner for up to 14 weeks. In the present open‐label extension study, the safety and efficacy of mirogabalin (administered using a flexible dosing of 10 or 15 mg twice daily) was shown over a longer period (52 weeks) in patients with DPNP, with >80% of the patients completing the extension study.…”

“…The protocol for the phase III study has been described elsewhere. Briefly, in the double‐blind, placebo‐controlled, parallel‐group study, 834 patients were randomized to receive fixed‐dosage mirogabalin 15, 20 or 30 mg/day, or placebo.…”

“…Mirogabalin has shown efficacy in patients with DPNP. Compared with placebo, mirogabalin significantly improved the average daily pain score in Asian patients with DPNP in a 14‐week phase III study. However, the long‐term efficacy and safety of mirogabalin remains unclear.…”

Short-Term Outcomes of Mirogabalin in Patients with Peripheral Neuropathic Pain: A Retrospective Study

“…Mirogabalin, a ligand for the α2δ subunit (α2δ-1 and α2δ-2) of voltage-sensitive calcium channels in the CNS, was approved as a medication for pain relief in patients with peripheral neuropathic pain in 2019 in Japan. Mirogabalin reportedly relieved diabetic peripheral neuropathic pain in a dose-dependent manner in Asian patients with diabetic peripheral neuropathic pain and was associated with only mild adverse events [30]. It was also shown to be effective and well tolerated in the management of postherpetic neuralgia in Asian patients [31].…”

Results of Mirogabalin Treatment for Diabetic Peripheral Neuropathic Pain in Asian Subjects: A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Study

“…Mirogabalin besylate (herein referred to as mirogabalin; Daiichi Sankyo Co., Ltd., Tokyo, Japan) was developed for the treatment of peripheral neuropathic pain, and was recently approved for this indication in Japan, based on the results of phase 3 studies [18][19][20]. Mirogabalin is an orally administered gabapentinoid that acts via a 2 d calcium channel subunits to modulate pain transmission and processing [21].…”