{"title":"克里斯卡巴林（HSK16149）对成人带状疱疹后神经痛的疗效和安全性：3期随机临床试验。","authors":"Daying Zhang, Tiechi Lei, Lanying Qin, Chenyu Li, Xuewu Lin, Huiping Wang, Guoqiang Zhang, Shoumin Zhang, Kemei Shi, Linfeng Li, Zhenling Yang, Xiumin Yang, Xiaohong Ba, Ying Gao, Zhuobo Zhang, Guonian Wang, Liming Wu, Yaping Wang, Yu Wang, Shoumin Zhu, Jihai Shi, Zhijian Ye, Chunjun Yang, Changyi Liu, Tong Zhang, Shousi Lu, Nan Yu, Xiangkui Li, Xiuping Han, Xiaoyan Chen, Li Wan, Zhigang Cheng, Nianyue Bai, Zhehu Jin, Chunshui Yu, Weiyi Zhang, Jianyun Lu, Dongmei Wang, Hui Sun, Wenzhong Wu, Pingping Qin, Zhiying Feng, Rixin Chen, Tangde Zhang, Dong Yang, Wenhao Yin, Jianglin Zhang, Xin Li, Fangqiong Li, Tingting Wu, Qianjin Lu","doi":"10.1001/jamadermatol.2024.3410","DOIUrl":null,"url":null,"abstract":"<p><strong>Importance: </strong>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.</p><p><strong>Objective: </strong>To investigate the efficacy and safety of crisugabalin, an oral calcium channel α2δ-1 subunit ligand, for postherpetic neuralgia.</p><p><strong>Design, setting, and participants: </strong>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).</p><p><strong>Interventions: </strong>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.</p><p><strong>Main outcome and measure: </strong>The primary efficacy end point was the change from baseline in ADPS at week 12.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions and relevance: </strong>Crisugabalin, 40 mg/d, or crisugabalin, 80 mg/d, was well tolerated and demonstrated a statistically significant improvement in ADPS over placebo.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT05140863.</p>","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":null,"pages":null},"PeriodicalIF":11.5000,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Efficacy and Safety of Crisugabalin (HSK16149) in Adults with Postherpetic Neuralgia: A Phase 3 Randomized Clinical Trial.\",\"authors\":\"Daying Zhang, Tiechi Lei, Lanying Qin, Chenyu Li, Xuewu Lin, Huiping Wang, Guoqiang Zhang, Shoumin Zhang, Kemei Shi, Linfeng Li, Zhenling Yang, Xiumin Yang, Xiaohong Ba, Ying Gao, Zhuobo Zhang, Guonian Wang, Liming Wu, Yaping Wang, Yu Wang, Shoumin Zhu, Jihai Shi, Zhijian Ye, Chunjun Yang, Changyi Liu, Tong Zhang, Shousi Lu, Nan Yu, Xiangkui Li, Xiuping Han, Xiaoyan Chen, Li Wan, Zhigang Cheng, Nianyue Bai, Zhehu Jin, Chunshui Yu, Weiyi Zhang, Jianyun Lu, Dongmei Wang, Hui Sun, Wenzhong Wu, Pingping Qin, Zhiying Feng, Rixin Chen, Tangde Zhang, Dong Yang, Wenhao Yin, Jianglin Zhang, Xin Li, Fangqiong Li, Tingting Wu, Qianjin Lu\",\"doi\":\"10.1001/jamadermatol.2024.3410\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Importance: </strong>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.</p><p><strong>Objective: </strong>To investigate the efficacy and safety of crisugabalin, an oral calcium channel α2δ-1 subunit ligand, for postherpetic neuralgia.</p><p><strong>Design, setting, and participants: </strong>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).</p><p><strong>Interventions: </strong>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.</p><p><strong>Main outcome and measure: </strong>The primary efficacy end point was the change from baseline in ADPS at week 12.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions and relevance: </strong>Crisugabalin, 40 mg/d, or crisugabalin, 80 mg/d, was well tolerated and demonstrated a statistically significant improvement in ADPS over placebo.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT05140863.</p>\",\"PeriodicalId\":14734,\"journal\":{\"name\":\"JAMA dermatology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":11.5000,\"publicationDate\":\"2024-09-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JAMA dermatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1001/jamadermatol.2024.3410\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DERMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JAMA dermatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1001/jamadermatol.2024.3410","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DERMATOLOGY","Score":null,"Total":0}
Efficacy and Safety of Crisugabalin (HSK16149) in Adults with Postherpetic Neuralgia: A Phase 3 Randomized Clinical Trial.
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.
期刊介绍：
JAMA Dermatology is an international peer-reviewed journal that has been in continuous publication since 1882. It began publication by the American Medical Association in 1920 as Archives of Dermatology and Syphilology. The journal publishes material that helps in the development and testing of the effectiveness of diagnosis and treatment in medical and surgical dermatology, pediatric and geriatric dermatology, and oncologic and aesthetic dermatologic surgery.
JAMA Dermatology is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications. It is published online weekly, every Wednesday, and in 12 print/online issues a year. The mission of the journal is to elevate the art and science of health and diseases of skin, hair, nails, and mucous membranes, and their treatment, with the aim of enabling dermatologists to deliver evidence-based, high-value medical and surgical dermatologic care.
The journal publishes a broad range of innovative studies and trials that shift research and clinical practice paradigms, expand the understanding of the burden of dermatologic diseases and key outcomes, improve the practice of dermatology, and ensure equitable care to all patients. It also features research and opinion examining ethical, moral, socioeconomic, educational, and political issues relevant to dermatologists, aiming to enable ongoing improvement to the workforce, scope of practice, and the training of future dermatologists.
JAMA Dermatology aims to be a leader in developing initiatives to improve diversity, equity, and inclusion within the specialty and within dermatology medical publishing.
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