口服舒达吡啶(WX-081)片对初治药物敏感肺结核和耐药肺结核早期杀菌活性、安全性和耐受性的Ⅱ期临床研究

doi:10.19983/j.issn.2096-8493.20260098

结核与肺部疾病杂志 2026, Vol. 7 Issue (5): 574-580 DOI: 10.19983/j.issn.2096-8493.20260098

口服舒达吡啶(WX-081)片对初治药物敏感肺结核和耐药肺结核早期杀菌活性、安全性和耐受性的Ⅱ期临床研究

曾春梅¹, 卢青霞¹, 聂文娟², 朱庆东¹(), 初乃惠²(), 朱凤梅¹()

¹ 南宁市第四人民医院结核科, 南宁 530023
² 首都医科大学附属北京胸科医院结核一科, 北京 101149

收稿日期:2026-05-12 出版日期:2026-10-20 发布日期:2026-10-19
通信作者: 朱庆东,初乃惠,朱凤梅 E-mail:zhuqingdong2003@163.com;dongchu1994@sina.com;59611427@qq.com
基金资助:
广西重点研发计划(桂科 AB25069097);北京市卫生健康委员会登峰项目(G202511062);北京市卫健委研究型病房卓越临床研究计划(BRWEP2024W042160109);北京市通州区科技计划项目(WS2025017)

A phase Ⅱ clinical study on the early bactericidal activity, safety, and tolerability of oral sudapyridine (WX-081) tablets in patients with newly diagnosed drug-susceptible and drug-resistant pulmonary tuberculosis

Zeng Chunmei¹, Lu Qingxia¹, Nie Wenjuan², Zhu Qingdong¹(), Chu Naihui²(), Zhu Fengmei¹()

¹ Department of Tuberculosis, Nanning Fourth People’s Hospital, Nanning 530023, China
² Department Ⅰ of Tuberculosis, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China

Received:2026-05-12 Online:2026-10-20 Published:2026-10-19
Contact: Zhu Qingdong,Chu Naihui,Zhu Fengmei E-mail:zhuqingdong2003@163.com;dongchu1994@sina.com;59611427@qq.com
Supported by:
Key Research and Development Program of Guangxi Zhuang Autonomous Region (Gui Ke AB25069097);Beijing Municipal Health Commission Dengfeng Program(G202511062);Beijing Municipal Health Commission Excellent Clinical Research Program for Research-oriented Wards(BRWEP2024W042160109);Beijing Tongzhou District Science and Technology Program Project(WS2025017)

摘要/Abstract

摘要：

背景: 耐药结核病是全球重大公共卫生挑战,治疗方案存在疗程长、不良反应多等问题。舒达吡啶(WX-081)是我国首个Ⅰ类抗结核新药,具有较好抗结核活性和相较贝达喹啉更好的安全性。方法: 本研究为一项全国随机、对照、多中心Ⅱ期临床试验,旨在评估口服舒达吡啶片对初治药物敏感肺结核和利福平耐药/耐多药肺结核患者的早期杀菌活性、安全性和耐受性,并初步评价其对耐药肺结核患者的有效性。研究通过收集单药治疗过程中,以及包含新药方案早期治疗后的痰菌菌落形成单位和痰培养报阳时间,观察变化趋势,并与经典治疗方案做比较,从而评价药物抗结核活性,并在治疗过程中收集安全性和耐受性数据用于评价用药安全。讨论: 本研究期望验证抗结核新药、优化耐药肺结核治疗方案,从而在保证抗结核活性的情况下提高用药安全性,进而为提高耐药肺结核治愈率提供理论依据和临床数据。

关键词: 抗结核药, 结核,抗多种药物性, 随机对照试验, 舒达吡啶

Abstract:

Background: Drug-resistant tuberculosis (TB) is a significant global public health challenge, with treatment regimens often characterized by long durations and numerous adverse effects. Sudapyridine (WX-081) is China’s first Class Ⅰ novel anti-tuberculosis drug, demonstrating good anti-tuberculosis activity and better safety compared to bedaquiline. Methods: This study is a national, randomized, controlled, multicenter Phase Ⅱ clinical trial, aiming to evaluate the early bactericidal activity, safety, and tolerability of oral sudapyridine tablets in patients with newly diagnosed drug-susceptible and drug-resistant pulmonary tuberculosis, and to preliminarily assess its effectiveness in patients with drug-resistant tuberculosis. The study collects data on sputum colony-forming units and time to positivity during monotherapy and early treatment with the new drug regimen, observing trends and comparing them with classic treatment regimens to evaluate anti-tuberculosis activity. Safety and tolerability data are also collected during treatment to assess the safety of the drug. Discussion: This study aims to validate the new anti-tuberculosis drug and optimize treatment regimens for drug-resistant pulmonary tuberculosis. By ensuring anti-tuberculosis activity while improving drug safety, it provides theoretical basis and clinical data to increase the cure rate of drug-resistant pulmonary tuberculosis.

Key words: Antitubercular agents, Tuberculosis, multidrug-resistant, Randomized controlled trial, Sudapyridine

中图分类号:

R521

曾春梅, 卢青霞, 聂文娟, 朱庆东, 初乃惠, 朱凤梅. 口服舒达吡啶(WX-081)片对初治药物敏感肺结核和耐药肺结核早期杀菌活性、安全性和耐受性的Ⅱ期临床研究[J]. 结核与肺部疾病杂志,2026, 7(5): 574-580. doi: 10.19983/j.issn.2096-8493.20260098

Zeng Chunmei, Lu Qingxia, Nie Wenjuan, Zhu Qingdong, Chu Naihui, Zhu Fengmei. A phase Ⅱ clinical study on the early bactericidal activity, safety, and tolerability of oral sudapyridine (WX-081) tablets in patients with newly diagnosed drug-susceptible and drug-resistant pulmonary tuberculosis[J]. Journal of Tuberculosis and Lung Disease, 2026, 7(5): 574-580. doi: 10.19983/j.issn.2096-8493.20260098

图/表 3

图1

表1

主要疗效指标研究阶段计划表

研究期	筛选期		住院期																		随访
访视	访视1	访视2 (电话)	住院药物治疗前		住院药物治疗阶段														住院药物治疗后		访视3
研究时间	-D14~ -D3	-D14~ -D3	-D2	-D1	D1	D2	D3	D4	D5	D6	D7	D8	D9	D10	D11	D12	D13	D14	D15	D16	D28
知情同意书签署	√
入选/排除标准	√
人口统计学资料	√
肺结核病史及药物治疗史	√
其他疾病史及药物治疗史^a	√
告知入院或药物洗脱^b		√
随机化分组			√
体格检查	√			√															√
生命体征	√			√	√	√	√	√	√	√	√	√	√	√	√	√	√	√
身高	√
体质量	√			√															√
12导联心电图	√			√							√								√
胸部CT平扫	√
血常规	√				√						√								√
尿液分析	√				√						√								√
粪常规+隐血	√																		√
尿妊娠试验^c	√				√
HIV及乙肝五项	√
电解质(Na、K、Cl、Ca、Mg、P)	√				√														√
血肌酐、血尿素氮和估算肾小球滤过率^d	√				√						√								√
血尿酸	√				√						√								√
肝功能检查(谷草转氨酶/谷丙转氨酶/总胆红素/碱性磷酸酶/谷氨酰转肽酶)	√				√						√								√
血淀粉酶					√														√
糖化血红蛋白(HbA1c)	√
血脂(甘油三酯、总胆固醇、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇)、空腹血糖	√				√														√
肌钙蛋白-Ⅰ					√														√
痰液采集^e	√			√	√	√	√	√	√	√	√	√		√		√		√
药代动力学血样采集					√													√	√	√
药物治疗					√	√	√	√	√	√	√	√	√	√	√	√	√	√
研究期间合并用药	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√
不良事件	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√

表1

表2

参考文献 10

[1]	World Health Organization. Global tuberculosis report 2024[R]. Geneva: World Health Organization, 2024.
[2]	Yao R, Wang B, Fu L, et al. Sudapyridine (WX-081), a Novel Compound against Mycobacterium tuberculosis[J]. Microbiol Spectr, 2022, 10(1):e0247721. doi:10.1128/spectrum.02477-21.
[3]	Yu C, Qian H, Wu Q, et al. Safety, pharmacokinetics, and food effect ofsudapyridine(WX-081), a novel anti-tuberculosis candidate in healthy Chinese subjects[J]. Clin Transl Sci, 2024, 17(2):e13718. doi:10.1111/cts.13718.
[4]	中国防痨协会, 《中国防痨杂志》编辑委员会, 首都医科大学附属北京胸科医院. 抗结核药物所致QTc间期延长临床监测和管理专家共识[J]. 中国防痨杂志, 2024, 46(1):8-17. doi:10.19982/j.issn.1000-6621.20230271.
[5]	Xiao H, Yu X, Shang Y, et al. In vitro and Intracellular Antibacterial Activity of Sudapyridine (WX-081) Against Tuberculosis[J]. Infect Drug Resist, 2023, 16:217-224. doi:10.2147/IDR.S390187. pmid: 36647451
[6]	李琦, 王宇津, 王雪钰, 等. 新型化合物舒达吡啶与克拉霉素药物代谢相互作用机制研究[J]. 中国防痨杂志, 2025, 47(2):142-149. doi:10.19982/j.issn.1000-6621.20240483.
[7]	Huang Z, Luo W, Xu D, et al. Discovery and preclinical profile of sudapyridine (WX-081), a novel anti-tuberculosis agent[J]. Bioorg Med Chem Lett, 2022, 71:128824. doi:10.1016/j.bmcl.2022.128824.
[8]	Gu Y, Nie W, Huang H, et al. Non-tuberculous mycobacterial disease: progress and advances in the development of novel candidate and repurposed drugs[J]. Front Cell Infect Microbiol, 2023, 13: 1243457. doi:10.3389/fcimb.2023.1243457.
[9]	Nie W, Gao S, Su L, et al. Antibacterial activity of the novel compound Sudapyridine (WX-081) against Mycobacterium abscessus[J]. Front Cell Infect Microbiol, 2023, 13:1217975. doi:10.3389/fcimb.2023.1217975.
[10]	Diacon A H, Donald P R, Pym A, et al. Randomized pilot trial of eight weeks of bedaquiline (TMC207) treatment for multidrug-resistant tuberculosis: long-term outcome, tolerability, and effect on emergence of drug resistance[J]. Antimicrob Agents Chemother, 2012, 56(6):3271-3276. doi:10.1128/AAC.06126-11. pmid: 22391540

[1]	方建庆, 沈瑜, 唐静雅, 武学农, 王哲, 余婷. 固本咳喘颗粒联合布地格福吸入气雾剂治疗脾肾两虚型老年慢性阻塞性肺疾病稳定期的临床观察[J]. 结核与肺部疾病杂志, 2026, 7(5): 608-614.
[2]	袁丽荣, 杨青龙, 李育玲, 李琳, 邓莎莎, 李淑花. 计算机化认知行为疗法在慢性阻塞性肺疾病患者症状群管理中的影响:一项随机对照试验[J]. 结核与肺部疾病杂志, 2024, 5(5): 476-483.
[3]	梁晨, 唐神结, 林明贵. 结核病综合治疗研究进展[J]. 结核与肺部疾病杂志, 2024, 5(1): 70-80.
[4]	周林, 刘二勇, 赵雁林. 选择适宜治疗方案正确评估抗结核治疗疗效提高利福平敏感结核病治疗质量[J]. 结核与肺部疾病杂志, 2023, 4(3): 189-193.
[5]	王国卫, 梁亚充, 刘宇飞, 李翠乔, 何萍. 消瘰散结散联合常规抗结核药物治疗浸润型淋巴结结核的疗效观察[J]. 结核与肺部疾病杂志, 2023, 4(1): 60-65.
[6]	董昭良, 姚黎明, 李领娣, 王连波, 姚晓伟, 李卓, 刘丰胜, 贾晨光. 保守方法治疗轻型脊柱结核的临床疗效[J]. 结核与肺部疾病杂志, 2022, 3(4): 281-286.
[7]	陈静, 赵鹏. 贵阳市7043例结核病患者发生抗结核药物性肝损伤的危险因素分析[J]. 结核与肺部疾病杂志, 2021, 2(4): 335-339.
[8]	顾宇人, 唐佩军. 抗结核药物性肝损伤相关危险因素研究进展[J]. 结核与肺部疾病杂志, 2021, 2(3): 283-288.
[9]	杨松,严晓峰. 抗结核药物诱导的药物超敏反应综合征研究进展[J]. 结核与肺部疾病杂志, 2017, 6(3): 293-281.
[10]	吴于青钟诚黄燕群宗佩兰. CD4+CD25+ 调节性T细胞在抗结核药物所致肝损伤中的作用[J]. 结核与肺部疾病杂志, 2017, 6(2): 125-127.
[11]	范向阳吴池林武振吕友娟杨荣黄碧陈锦春. 抗结核固定剂量复合制剂联合抗肺痨散治疗初治涂阳肺结核的临床疗效[J]. 结核与肺部疾病杂志, 2017, 6(2): 135-140.
[12]	金弢. 临床行血液净化患者的抗结核药物使用规则[J]. 结核与肺部疾病杂志, 2017, 6(1): 21-24.
[13]	邓国防，孙丽珍，唐怡敏，张培泽，詹森林，陈涛，叶涛生. 主要高危人群抗结核治疗不良反应发生情况分析[J]. 结核与肺部疾病杂志, 2015, 4(4): 215-218.
[14]	韩娜，李占英，田艳卿. 组合抗结核药物致过敏性皮疹32例临床分析[J]. 结核与肺部疾病杂志, 2015, 4(4): 239-241.
[15]	张云玲，阚晓红. 40例复发性肺结核患者抗结核药物治疗不良反应的临床分析[J]. 结核与肺部疾病杂志, 2015, 4(4): 242-246.

口服舒达吡啶(WX-081)片对初治药物敏感肺结核和耐药肺结核早期杀菌活性、安全性和耐受性的Ⅱ期临床研究

A phase Ⅱ clinical study on the early bactericidal activity, safety, and tolerability of oral sudapyridine (WX-081) tablets in patients with newly diagnosed drug-susceptible and drug-resistant pulmonary tuberculosis

RichHTML

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

图/表 3

参考文献 10

相关文章 15

编辑推荐

Metrics

本文评价

研究期	门诊治疗期					随访期
访视	访视1	访视2	访视3	访视4	访视5	访视6
研究时间	D15~D21 (第1周)	D22~D28 (第2周)	D36~D42 (第4周)	D43~D49 (第5周)	D50~D56 (第6周)	D57~D84 (第10周)
体格检查		√			√
生命体征	√	√	√	√	√
体质量					√
12导联心电图		√	√		√
血常规		√			√
尿液分析		√			√
电解质(Na、K、Cl、Ca、Mg、P)		√			√
血肌酐、血尿素氮和估算肾小球滤过率		√			√
血尿酸		√			√
肝功能检查(谷草转氨酶/谷丙转氨酶/总胆红素/碱性磷酸酶/谷氨酰转肽酶)		√			√
血淀粉酶/肌钙蛋白-Ⅰ					√
血脂(甘油三酯、总胆固醇、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇)、空腹血糖					√
痰液采集	√	√	√	√	√
药物发放治疗及核算	√	√	√	√	√
合并用药	√	√	√	√	√	√
不良事件	√	√	√	√	√	√