GABA Analogue HSK16149 in Chinese Patients With Diabetic Peripheral Neuropathic Pain

医学 普瑞巴林 安慰剂 临床试验 临床终点 随机对照试验 不利影响 神经病理性疼痛 阶段(地层学) 麻醉 内科学 古生物学 替代医学 病理 生物
作者
Xiaohui Guo,Tingting Zhang,Yang Yu,Wei‐Fang Zeng,Qingyuan Hu,Jianhua Ma,Yukun Li,Hongmei Li,Yawei Zhang,Jie Liu,Fang Bian,Wei Zhang,Fang Zhang,Shuguang Pang,Yanan Li,Xiaohong Wu,Xulei Tang,Keqin Zhang,Tianrong Pan,Honglin Hu,Zhifeng Cheng,Yanjun Wang,Jialin Gao,Jia Sun
出处
期刊:JAMA network open [American Medical Association]
卷期号:7 (8): e2425614-e2425614
标识
DOI:10.1001/jamanetworkopen.2024.25614
摘要

Importance Many patients with diabetic peripheral neuropathic pain (DPNP) experience inadequate relief, despite best available medical treatments. There are no approved and effective therapies for patients with DPNP in China. Objective To evaluate the efficacy and safety of capsules containing γ-aminobutyric acid (GABA) analogue HSK16149 in the treatment of Chinese patients with DPNP. Design, Setting, and Participants This phase 2 to 3 adaptive randomized clinical trial was multicenter, double blind, and placebo and pregabalin controlled. The trial started on December 10, 2020, and concluded on July 8, 2022. In stage 1, various doses of HSK16149 were evaluated to determine safety and efficacy for stage 2. The second stage then validated the efficacy and safety of the recommended dose. Intervention In stage 1, enrolled patients (n = 363) were randomized 1:1:1:1:1:1 to 4 HSK16149 doses (40, 80, 120, or 160 mg/d), pregabalin (300 mg/d), or placebo. In stage 2, patients (n = 362) were randomized 1:1:1 to receive HSK16149, 40 or 80 mg/d, or placebo. The final efficacy and safety analysis pooled data from patients receiving the same treatment. Main Outcomes and Measures The primary efficacy end point in stage 1 was the change from baseline in average daily pain score (ADPS) at week 5. The primary efficacy end point in stage 2 was the change from baseline in ADPS at week 13. When the final statistical analysis was performed, the P values calculated from the independent data of each phase were combined using the weighted inverse normal method to make statistical inferences. Results Of 725 randomized patients in the full-analysis set (393 men [54.2%]; mean [SD] age, 58.80 [9.53] years; 700 [96.6%] of Han Chinese ethnicity), 177 received placebo; 178, HSK16149, 40 mg/d; 179, HSK16149, 80 mg/d; 66, HSK16149, 120 mg/d; 63, HSK16149, 160 mg/d; and 62, pregabalin, 300 mg/d. A total of 644 patients (88.8%) completed the study. The 40- and 80-mg/d doses of HSK16149 were recommended in stage 2. At week 13, the ADPS mean (SD) change from baseline was −2.24 (1.55) for the 40-mg/d and −2.16 (1.79) for 80-mg/d groups and −1.23 (1.68) for the placebo group, showing statistical significance for both HSK16149 doses vs placebo (both P < .001). In a safety set (n = 726), 545 patients (75.1%) had adverse events, which were generally mild to moderate, with dizziness and somnolence being the most common. Conclusions and Relevance Forty- and eighty-mg/d doses of HSK16149 were recommended for treating patients with DPNP in China. The efficacy of HSK16149 capsules was superior to placebo in all groups for relieving DPNP and appeared well tolerated. Trial Registration ClinicalTrials.gov Identifier: NCT04647773
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
海儿的小宝贝完成签到,获得积分10
4秒前
nicezhutou完成签到 ,获得积分10
8秒前
姚姚完成签到 ,获得积分10
13秒前
松柏完成签到 ,获得积分10
14秒前
飞龙在天完成签到,获得积分0
15秒前
达斯维完成签到,获得积分10
17秒前
榆木小鸟完成签到 ,获得积分10
21秒前
学习要认真喽完成签到,获得积分10
24秒前
无情夏寒完成签到 ,获得积分10
25秒前
guo完成签到 ,获得积分10
26秒前
闻屿完成签到,获得积分10
27秒前
Ashley完成签到 ,获得积分10
33秒前
ytrewq完成签到 ,获得积分10
36秒前
Minjalee完成签到,获得积分0
38秒前
冷傲鸡翅完成签到,获得积分10
39秒前
干的不错完成签到 ,获得积分10
43秒前
路路完成签到 ,获得积分10
44秒前
郑雅柔完成签到 ,获得积分10
48秒前
无与伦比完成签到 ,获得积分10
49秒前
wanci应助satchzhao采纳,获得10
57秒前
今天开心吗完成签到 ,获得积分10
1分钟前
yzhilson完成签到 ,获得积分10
1分钟前
青山完成签到 ,获得积分10
1分钟前
非我完成签到 ,获得积分10
1分钟前
沉默采波完成签到 ,获得积分10
1分钟前
mp5完成签到,获得积分10
1分钟前
CH完成签到,获得积分10
1分钟前
nianshu完成签到 ,获得积分10
1分钟前
贤惠的紫菜完成签到 ,获得积分10
1分钟前
T_MC郭完成签到,获得积分10
1分钟前
毛豆爸爸完成签到,获得积分0
1分钟前
1分钟前
satchzhao发布了新的文献求助10
1分钟前
Even9完成签到,获得积分10
1分钟前
坚强的广山应助科研通管家采纳,获得200
1分钟前
zjhzslq完成签到,获得积分10
1分钟前
青羽落霞完成签到 ,获得积分10
1分钟前
自由冬亦完成签到,获得积分10
1分钟前
1分钟前
贾舒涵完成签到,获得积分10
1分钟前
高分求助中
The late Devonian Standard Conodont Zonation 2000
Nickel superalloy market size, share, growth, trends, and forecast 2023-2030 2000
The Lali Section: An Excellent Reference Section for Upper - Devonian in South China 1500
Smart but Scattered: The Revolutionary Executive Skills Approach to Helping Kids Reach Their Potential (第二版) 1000
Very-high-order BVD Schemes Using β-variable THINC Method 850
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 800
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 800
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3248865
求助须知:如何正确求助?哪些是违规求助? 2892249
关于积分的说明 8270316
捐赠科研通 2560537
什么是DOI,文献DOI怎么找? 1389048
科研通“疑难数据库(出版商)”最低求助积分说明 651004
邀请新用户注册赠送积分活动 627850