Long-Term Safety and Efficacy of Mirogabalin for Central Neuropathic Pain: A Multinational, Phase 3, 52-Week, Open-Label Study in Asia

Takahiro Ushida; Yoichi Katayama; Yoichi Hiasa; Makoto Nishihara; Fumihiro Tajima; Shinsuke Katoh; Hirotaka Tanaka; Takeshi Maeda; Kazunari Furusawa; Yoshihiro Kakehi; Kunika Kikumori; Masanori Kuroha

doi:10.1007/s40122-023-00513-1

Long-Term Safety and Efficacy of Mirogabalin for Central Neuropathic Pain: A Multinational, Phase 3, 52-Week, Open-Label Study in Asia

Pain Ther. 2023 Aug;12(4):963-978. doi: 10.1007/s40122-023-00513-1. Epub 2023 Apr 28.

Authors

Affiliations

¹ Multidisciplinary Pain Center, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi, 480-1195, Japan.
² Department of Neurological Surgery, Nihon University School of Medicine, 30-1 Oyaguchi Kami-Cho, Itabashi, Tokyo, 173-8610, Japan.
³ Center for Brain and Health Sciences, Aomori University, 2-3-1 Kobata, Aomori, Aomori, 030-0943, Japan.
⁴ Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan.
⁵ Department of Rehabilitation Medicine, Wakayama Medical University, 811-1 Kimiidera Wakayama, Wakayama, 641-8509, Japan.
⁶ Red Cross Tokushima Hinomine Rehabilitation Center for People with Disabilities, 4-1 Shinbiraki, Chudencho, Komatsushima, Tokushima, 773-0015, Japan.
⁷ Department of Rehabilitation, Chubu Rosai Hospital, 1-10-6 Koumei, Minato, Nagoya, Aichi, 455-8530, Japan.
⁸ Spinal Injuries Center, 550-4 Igisu, Iizuka, Fukuoka, 820-8508, Japan.
⁹ Kibikogen Rehabilitation Center for Employment Injuries, 7511 Yoshikawa, Kibichuou-Cho, Kaga, Okayama, 716-1241, Japan.
¹⁰ Clinical Development Department II, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa, Tokyo, 140-8710, Japan.
¹¹ Data Intelligence Department, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa, Tokyo, 140-8710, Japan.
¹² Oncology Medical Science Department, Daiichi Sankyo Co., Ltd., 3-5-1, Nihonbashi Honcho, Chuo-Ku, Tokyo, 103-8426, Japan. kuroha.masanori.kh@daiichisankyo.co.jp.

Abstract

Introduction: Central neuropathic pain (CNeP) is difficult to treat and has diverse etiology, including spinal cord injury (CNePSCI), Parkinson's disease (CNePPD), and central post-stroke pain (CPSP). The safety and efficacy of mirogabalin have been demonstrated in short-term trials, including patients with CNePSCI. The objective of our study was to confirm the safety/efficacy of mirogabalin in patients with CNePPD and CPSP, and obtain long-term data for CNePSCI.

Methods: This 52-week, open-label extension of a previous randomized controlled study was conducted across Japan, Korea, and Taiwan. Patients with CNePSCI, CNePPD, or CPSP received twice daily (BID) 5-10 mg mirogabalin for a 4-week titration period, after which the dosage was maintained for 47 weeks at a maximum of 15 mg BID, followed by a 1-week taper period receiving the same dose but only administered once daily. The primary endpoint was safety, assessed primarily by incidence and severity of treatment-emergent adverse events (TEAEs). Efficacy was assessed in a post hoc analysis of data obtained by the short-form McGill Pain Questionnaire (SF-MPQ).

Results: Of the 210 patients enrolled, 106, 94, and 10 had CNePSCI, CPSP, and CNePPD, respectively. The mean overall age of patients was 62.9 years, and most patients were male and of Japanese ethnicity. TEAEs occurred in 84.8% of patients, the most common being somnolence (16.7%), peripheral edema (12.4%), edema (11.4%), nasopharyngitis (11.0%), and dizziness (7.6%). Most TEAEs were mild. Severe and serious TEAEs occurred in 6.2% and 13.3% of patients, respectively. All patient groups experienced reductions in SF-MPQ visual analog scores for pain: mean ± standard deviation changes from baseline at week 52 were -2.3 ± 21.13 mm (CNePSCI), -17.0 ± 24.99 mm (CPSP), and -17.1 ± 35.32 mm (CNePPD).

Conclusion: Mirogabalin was generally safe, well tolerated, and effective for treatment of CNeP in this long-term study.

Trial registration: ClinicalTrials.gov identifier, NCT03901352.

Keywords: Central neuropathic pain; Efficacy; Gabapentinoid; Mirogabalin; Open-label; Parkinson’s disease; Post-stroke pain; Safety; Spinal cord injury.

Associated data

ClinicalTrials.gov/NCT03901352