Efficacy and Safety of Crisugabalin (HSK16149) in Adults with Postherpetic Neuralgia: A Phase 3 Randomized Clinical Trial.
Zhenling Yang, Weiyi Zhang, Yu Wang, Wenhao Yin, Chunshui Yu, Zhehu Jin, Zhiying Feng, Daying Zhang, Tiechi Lei, Lanying Qin, Xuewu Lin, Shoumin Zhang, Kemei Shi, Xin Li, Xiumin Yang, Xiaohong Ba, Guonian Wang, Shoumin Zhu, Jihai Shi, Zhijian Ye, Chunjun Yang, Shousi Lu, Nianyue Bai, Pingping Qin, Tangde Zhang, Fangqiong Li, Xiaoyan Chen, Zhigang Cheng, Tingting Wu, Wenzhong Wu, Rixin Chen, Liming Wu, Zhuobo Zhang, Guoqiang Zhang, Huiping Wang, Xiuping Han, Qianjin Lu, Linfeng Li, Changyi Liu, Xiangkui Li, Nan Yu, Jianyun Lu, Tong Zhang, Chenyu Li, Yaping Wang, Jianglin Zhang, Dongmei Wang, Ying Gao, Dong Yang, Li Wan, Hui Sun
Journal: JAMA dermatology
2024;160(11):1182-1191
PMID: 39320907
Abstract
IMPORTANCE
China carries a heavy burden of postherpetic neuralgia, with an unmet need for novel drugs with greater efficacy and less prominent neurotoxic effects than existing calcium channel ligands.
OBJECTIVE
To investigate the efficacy and safety of crisugabalin, an oral calcium channel α2δ-1 subunit ligand, for postherpetic neuralgia.
DESIGN, SETTING, AND PARTICIPANTS
This randomized clinical trial, carried out between November 9, 2021, and January 5, 2023, at 48 tertiary care centers across China had 2 parts. Part 1 was a phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study consisting of a 2-week screening period, a 7-day run-in period, and a 12-week double-blind treatment period. Part 2 was a 14-week open-label extension study. Investigators, statisticians, trial clinicians, and patients were blinded to trial group assignments. Participants included adults with postherpetic neuralgia with an average daily pain score (ADPS) of at least 4 on the 11-point Numeric Pain Rating Scale over the preceding week, with the exclusion of patients with pain not controlled by prior therapy with pregabalin (≥300 mg/d) or gabapentin (≥1200 mg/d).
INTERVENTIONS
Patients were randomized 1:1:1 to receive crisugabalin, 20 mg twice daily (ie, 40 mg/d), and crisugabalin, 40 mg twice daily (ie, 80 mg/d), or placebo for 12 weeks. Eligible patients received crisugabalin, 40 mg, twice daily during extension.
MAIN OUTCOME AND MEASURE
The primary efficacy end point was the change from baseline in ADPS at week 12.
RESULTS
The study enrolled 366 patients (121 patients receiving crisugabalin, 40 mg/d; 121 patients receiving crisugabalin, 80 mg/d; 124 patients receiving placebo; median [IQR] age, 63.0 [56.0-69.0] years; 193 men [52.7%]). At week 12, the least squares mean (SD) change from baseline in ADPS was -2.2 (0.2) for crisugabalin, 40 mg/d, and -2.6 (0.2) for crisugabalin, 80 mg/d, vs -1.1 (0.2) for placebo, with a least squares mean difference of -1.1 (95% CI, -1.6 to -0.7; P < .001) and -1.5 (-95% CI, -2.0 to -1.0; P < .001) vs placebo, respectively. No new safety concerns emerged.
CONCLUSIONS AND RELEVANCE
Crisugabalin, 40 mg/d, or crisugabalin, 80 mg/d, was well tolerated and demonstrated a statistically significant improvement in ADPS over placebo.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT05140863.
Address:
Department of Pain Medicine, The First Affiliated Hospital of Nanchang University, Donghu District, Nanchang, Jiangxi, China.; Department of Dermatology, Renmin Hospital of Wuhan University, Wuchang District, Wuhan, Hubei, China.; Department of Dermatology, Cangzhou People's Hospital, Cangzhou, Hebei, China.; Department of Neurology, Chongqing Traditional Chinese Medicine Hospital, Panxi, Jiangbei District, Chongqing, China.; Department of Anaesthesiology, The First Affiliated Hospital of Bengbu Medical University, Longzihu District, Bengbu, Anhui Province, China.; Department of Dermatovenereology, Tianjin Medical University General Hospital, Heping District, Tianjin, China.; Department of Dermatology, The First Hospital of Hebei Medical University, Yuhua District, Shijiazhuang, Hebei Province, China.; Department of Dermatology, Henan Provincial People's Hospital, Zhengzhou, Henan Province, China.; Pain Management Center, The Second Hospital of Tianjin Medical University, Hexi District, Tianjin, China.; Department of Dermatology, Beijing Friendship Hospital, Capital Medical University, Xicheng District, Beijing, China.; Department of Pain, The First of Affiliated Hospital of Henan University, Kaifeng, Henan, China.; Department of Dermatology, Beijing Tongren Hospital, Capital Medical University, Dongcheng District, Beijing, China.; Department of Neurology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China.; Department of Dermatology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Jiang'an District, Wuhan, Hubei, China.; Department of Neurology, The Fourth Hospital of Harbin Medical University, Nangang District, Harbin, Heilongjiang, China.; Department of Anesthesiology, The Fourth Hospital of Harbin Medical University, Nangang District, Harbin, Heilongjiang, China.; Department of Dermatology and Venereology, Affiliated Hangzhou First People's Hospital, Hangzhou, Zhejiang, China.; Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.; Department of Dermatology, The Affiliated Hospital of Guizhou Medical University, Yunyan District, Guiyang, Guizhou, China.; Department of Dermatology, People's Hospital Affiliated to Chongqing Three Gorges Medical College, Wanzhou District, Chongqing, China.; Department of Dermatology, The First Affiliated Hospital of Baotou Medical College, Kundulun District, Baotou, Inner Mongolia Autonomous Region, China.; Department of Anesthesiology, The Affiliated Jinhua Hospital of Wenzhou Medical University, Jindong District, Jinhua, Zhejiang, China.; Department of Dermatology and Venereology, The Second Affiliated Hospital of Anhui Medical University, Shushan District, Hefei, Anhui, China.; Department of Neurology, The First Hospital of Qiqihar, Longsha District, Qiqihar, Heilongjiang, China.; Department of Neurology, Research Ward, China Rehabilitation Research Center, Fengtai District, Beijing, China.; Research Ward, China Rehabilitation Research Center, Fengtai District, Beijing, China.; Department of Dermatology, General Hospital of Ningxia Medical University, Xingqing Area, Ningxia, Ningxia Hui Autonomous Region, China.; Department of Anesthesiology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Qingyang District, Chengdu, Sichuan, China.; Department of Dermatology, Shengjing Hospital of China Medical University, Heping District Shenyang, Liaoning, China.; Department of Dermatology, Xianyang Hospital of Yan'an University, Weicheng District, Xianyang, Shaanxi, China.; Pain Management Department, The Second Affiliated Hospital of Guangzhou Medical University, Haizhu District, Guangzhou, Guangdong, China.; Department of Anesthesiology, Xiangya Hospital Central South University, Changsha, Hunan, China.; Xiangya Hospital, Central South University, Changsha, Hunan, China.; Department of Dermatology, The Affiliated Hospital of Yanbian University (Yanbian Hospital), Yanji, Jilin, China.; Department of Dermatology, Suining Central Hospital, Chuanshan District, Suining, Sichuan, China.; Department of Anesthesiology, West China Hospital, Sichuan University, Wuhou District, Chengdu, Sichuan, China.; Department of Dermatology, The Third Xiangya Hospital of Central South University, Yuelu District, Changsha, Hunan, China.; Department of Chinese Medicine Dermatology, Dermatology Hospital of Southern Medical University, Yuexiu District, Guangzhou, Guangdong, China.; Department of Dermatology, Wuxi Second People's Hospital, Liangxi District, Wuxi, Jiangsu, China.; Department of Dermatology, Shenzhen Second People's Hospital, Futian District, Shenzhen, Guangdong, China.; Department of Dermatology, Yancheng No.1 People's Hospital, Yancheng, Hubei, China.; Department of Pain Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.; Department of Dermatology, Nanyang First People's Hospital, Nanyang, Henan, China.; Department of Dermatology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China.; Department of Pain Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.; Department of Dermatology, The First Hospital of Jiaxing, Jiaxing, Zhejiang Province, China.; Department of Dermatology, Shenzhen People's Hospital, Luohu District, Shenzhen, Guangdong, China.; Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.; Haisco Pharmaceutical Group Co, Ltd, Wenjiang District, Chengdu, Sichuan, China.; Hospital for Skin Diseases (Institute of Dermatology), Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China.
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MeSH Terms:
Humans,
Neuralgia, Postherpetic,
Male,
Double-Blind Method,
Female,
Middle Aged,
Aged,
Treatment Outcome,
Pain Measurement,
China,
Adult,
Analgesics
