A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled 14-Week Study of Mirogabalin in Chinese Patients with Diabetic Peripheral Neuropathic Pain

Xiaohui Guo; Yang Yu; Yongbo Zhang; Li Sun; Yufeng Li; Bing Song; Li Hang; Masayuki Baba; Yosuke Wasaki; Kunika Kikumori; Emiko Murayama

doi:10.1007/s40122-024-00617-2

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled 14-Week Study of Mirogabalin in Chinese Patients with Diabetic Peripheral Neuropathic Pain

Pain Ther. 2024 Aug;13(4):937-952. doi: 10.1007/s40122-024-00617-2. Epub 2024 Jun 19.

Authors

Xiaohui Guo¹, Yang Yu², Yongbo Zhang³, Li Sun⁴, Yufeng Li⁵, Bing Song⁶, Li Hang⁷, Masayuki Baba⁸, Yosuke Wasaki⁹, Kunika Kikumori¹⁰, Emiko Murayama¹¹

Affiliations

¹ Department of Endocrinology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China. bdyyguoxiaohui@sina.com.
² Department of Endocrinology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, China.
³ Department of Neurology, Beijing Friendship Hospital, Capital Medical University, No. 95 Yongan Road, Beijing, 100050, China.
⁴ Siping Central People's Hospital, No. 89 South Yingbin Street, Tiexie District, Siping, 136000, Jilin Province, China.
⁵ Beijing Pinggu Hospital, No. 59 Xingping North Road, Pinggu District, Beijing, 101200, China.
⁶ The First Affiliated Hospital of Jinzhou Medical University, Guta District, No. 2, 5H Part, Renmin Street, Liaoning Province 121001, Jinzhou City, China.
⁷ Daiichi Sankyo (China) Holdings Co., Ltd, Floor 51, Wheelock Square, 1717 Nanjing West Road, Shanghai, 200040, China.
⁸ Neurology Center, Aomori Prefectural Central Hospital, 2-1-1 Higashitsukurimichi, Aomori, 030-8553, Japan.
⁹ Asset Portfolio Management Department, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa, Tokyo, 140-8710, Japan.
¹⁰ Data Intelligence Department, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa, Tokyo, 140-8710, Japan.
¹¹ Specialty Medicine Clinical Development Department, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa, Tokyo, 140-8710, Japan.

Abstract

Introduction: There is no approved effective drug for diabetic peripheral neuropathic pain (DPNP) in China. Gabapentinoids including mirogabalin have shown promise, although data in Chinese patients are scarce.

Methods: This phase 3, multicenter, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of mirogabalin for treating DPNP in China. Mirogabalin was administered at 5 mg twice daily for the first week and uptitrated to 15 mg twice daily for a total duration of 14 weeks. The primary efficacy endpoint was the change from baseline in weekly average daily pain score (ADPS) at week 14; secondary endpoints included the ADPS responder rate, Short-Form McGill Pain Questionnaire visual analogue scale score, patient global impression of change (PGIC), average daily sleep interference score (ADSIS), EuroQol 5-dimensions 5-levels (EQ-5D-5L), and incidence of treatment-emergent adverse events (TEAEs).

Results: Of 393 patients (mirogabalin, n = 196; placebo n = 197), the mean age was 58.2 years (mirogabalin, 58.7 years; placebo, 57.7 years) and 54.2% were male (mirogabalin, 56.1%; placebo, 52.3%). Mirogabalin elicited a greater change from baseline in the weekly ADPS vs. placebo at week 14: least-squares mean difference (95% confidence interval) vs. placebo - 0.39 (- 0.74, - 0.04), p = 0.0301. PGIC, ADSIS, and EQ-5D-5L data reflected significantly better improvements for patients receiving mirogabalin vs. placebo. The incidence of TEAEs was 75.0% and 75.1% in the mirogabalin and placebo groups, respectively. Most TEAEs were mild or moderate, and the incidence of TEAEs leading to treatment discontinuation was 2.6% in the mirogabalin group and 1.5% in the placebo group.

Conclusions: Although the effect size of mirogabalin was reduced due to the placebo effect, mirogabalin is a safe and effective treatment option for Chinese patients with DPNP.

Trial registration: ClinicalTrials.gov identifier, NCT04094662.

Keywords: China; Diabetes complications; Mirogabalin; Neuralgia; Phase 3.

Associated data

ClinicalTrials.gov/NCT04094662