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

doi:10.1007/s40122-024-00617-2

. 2024 Aug;13(4):937-952.

doi: 10.1007/s40122-024-00617-2. Epub 2024 Jun 19.

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

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. [email protected].
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.

PMID: 38896199
PMCID: PMC11255142
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

Xiaohui Guo et al. Pain Ther. 2024 Aug.

. 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. [email protected].
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.

PMID: 38896199
PMCID: PMC11255142
DOI: 10.1007/s40122-024-00617-2

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.

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Conflict of interest statement

Xiaohui Guo, Yang Yu, Yongbo Zhang, Li Sun, Yufeng Li, and Bing Song received investigator fees from Daiichi Sankyo Co., Ltd. Masayuki Baba received lecture and consultancy fees from Daiichi Sankyo Co., Ltd. Yosuke Wasaki, Kunika Kikumori, and Emiko Murayama are employees of the study sponsor, Daiichi Sankyo Co., Ltd., and Li Hang is an employee of Daiichi Sankyo (China) Holdings Co., Ltd.

Figures

**Fig. 1**
Study design. Patients underwent screening at visit 1, at which demographics and baseline data were collected and physical exams were performed. Patients were also instructed on the use of electronic diaries and completed SF-MPQ, HADS, and C-SSRS. At visit 2 (observation), patient diaries were reviewed. Patients were randomly allocated to treatment groups at visit 3 and underwent minimal physical exams, laboratory tests, and completed SF-MPQ, HADS, EQ-5D-5L, C-SSRS, and MOS-Sleep evaluations. Patients attended the study site every week for visits 3–5 and every 2 weeks for visits 6–10 during the treatment period. At visit 11 (end of treatment), patients underwent full physical exams, laboratory tests, and completed SF-MPQ, PGIC, HADS, EQ-5L-5D, C-SSRS, and MOS-Sleep evaluations. Post-treatment follow-up was conducted at visit 12 and included the HADS and C-SSRS evaluations, as well as physical exams and laboratory tests. *BID* twice daily, *C-SSRS* Colombia-Suicide Severity Rating Scale, *HADS* Hospital Anxiety and Depression Scale, IC informed consent, *MOS-Sleep* Medical Outcomes Study Sleep Scale, *PGIC* patient global impression of change, *SF-MPQ* Short-Form McGill Pain Questionnaire

**Fig. 2**
Patient disposition. ^aIncludes discontinuations due to the COVID-19 pandemic. *mITT* modified intention-to-treat

**Fig. 3**
Time-course of least-squares mean weekly average daily pain score (modified intention-to-treat analysis set). Data were imputed using a multiple imputation method using a pattern mixture model with shifting parameters of [adverse event, lack of efficacy, any other reason] = [1.0, 1.0, 0.5] and a mixed-effects model for repeated measures. Data are least-squares mean with standard error. 0 = no pain; 10 = worst pain imaginable

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References

1. Gylfadottir SS, Weeracharoenkul D, Andersen ST, Niruthisard S, Suwanwalaikorn S, Jensen TS. Painful and non-painful diabetic polyneuropathy: Clinical characteristics and diagnostic issues. J Diabetes Investig. 2019;10:1148–1157. doi: 10.1111/jdi.13105. - DOI - PMC - PubMed
1. Gore M, Brandenburg NA, Dukes E, Hoffman DL, Tai KS, Stacey B. Pain severity in diabetic peripheral neuropathy is associated with patient functioning, symptom levels of anxiety and depression, and sleep. J Pain Symptom Manage. 2005;30:374–385. doi: 10.1016/j.jpainsymman.2005.04.009. - DOI - PubMed
1. Tesfaye S, Vileikyte L, Rayman G, et al. Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management. Diabetes Metab Res Rev. 2011;27:629–638. doi: 10.1002/dmrr.1225. - DOI - PubMed
1. Girach A, Julian TH, Varrassi G, Paladini A, Vadalouka A, Zis P. Quality of life in painful peripheral neuropathies: a systematic review. Pain Res Manag. 2019;2019:2091960. doi: 10.1155/2019/2091960. - DOI - PMC - PubMed
1. Treede RD, Jensen TS, Campbell JN, et al. Neuropathic pain: Redefinition and a grading system for clinical and research purposes. Neurology. 2008;70:1630–1635. doi: 10.1212/01.wnl.0000282763.29778.59. - DOI - PubMed

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[1] Gylfadottir SS, Weeracharoenkul D, Andersen ST, Niruthisard S, Suwanwalaikorn S, Jensen TS. Painful and non-painful diabetic polyneuropathy: Clinical characteristics and diagnostic issues. J Diabetes Investig. 2019;10:1148–1157. doi: 10.1111/jdi.13105. - DOI - PMC - PubMed

[2] Gylfadottir SS, Weeracharoenkul D, Andersen ST, Niruthisard S, Suwanwalaikorn S, Jensen TS. Painful and non-painful diabetic polyneuropathy: Clinical characteristics and diagnostic issues. J Diabetes Investig. 2019;10:1148–1157. doi: 10.1111/jdi.13105. - DOI - PMC - PubMed

[3] Gore M, Brandenburg NA, Dukes E, Hoffman DL, Tai KS, Stacey B. Pain severity in diabetic peripheral neuropathy is associated with patient functioning, symptom levels of anxiety and depression, and sleep. J Pain Symptom Manage. 2005;30:374–385. doi: 10.1016/j.jpainsymman.2005.04.009. - DOI - PubMed

[4] Gore M, Brandenburg NA, Dukes E, Hoffman DL, Tai KS, Stacey B. Pain severity in diabetic peripheral neuropathy is associated with patient functioning, symptom levels of anxiety and depression, and sleep. J Pain Symptom Manage. 2005;30:374–385. doi: 10.1016/j.jpainsymman.2005.04.009. - DOI - PubMed

[5] Tesfaye S, Vileikyte L, Rayman G, et al. Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management. Diabetes Metab Res Rev. 2011;27:629–638. doi: 10.1002/dmrr.1225. - DOI - PubMed

[6] Tesfaye S, Vileikyte L, Rayman G, et al. Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management. Diabetes Metab Res Rev. 2011;27:629–638. doi: 10.1002/dmrr.1225. - DOI - PubMed

[7] Girach A, Julian TH, Varrassi G, Paladini A, Vadalouka A, Zis P. Quality of life in painful peripheral neuropathies: a systematic review. Pain Res Manag. 2019;2019:2091960. doi: 10.1155/2019/2091960. - DOI - PMC - PubMed

[8] Girach A, Julian TH, Varrassi G, Paladini A, Vadalouka A, Zis P. Quality of life in painful peripheral neuropathies: a systematic review. Pain Res Manag. 2019;2019:2091960. doi: 10.1155/2019/2091960. - DOI - PMC - PubMed

[9] Treede RD, Jensen TS, Campbell JN, et al. Neuropathic pain: Redefinition and a grading system for clinical and research purposes. Neurology. 2008;70:1630–1635. doi: 10.1212/01.wnl.0000282763.29778.59. - DOI - PubMed

[10] Treede RD, Jensen TS, Campbell JN, et al. Neuropathic pain: Redefinition and a grading system for clinical and research purposes. Neurology. 2008;70:1630–1635. doi: 10.1212/01.wnl.0000282763.29778.59. - DOI - PubMed

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

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

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