更新于：2024-09-06
Lesogaberan
更新于：2024-09-06
概要
基本信息
原研机构 |
在研机构- |
最高研发阶段无进展临床2期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
结构
分子式C3H9FNO2P |
InChIKeyLJNUIEQATDYXJH-GSVOUGTGSA-N |
CAS号344413-67-8 |
关联
15
项与 Lesogaberan 相关的临床试验The Role of GABAb receptor mechanisms in cough: Double-blind randomised controlled trial of Lesogaberan in Chronic cough patients with positive and negative symptom association probabilities - GARMIN-II: double-blind randomised controlled trial of lesogaberan in cough
Efficacy and Safety of Lesogaberan (AZD3355) in Chinese Patients With Reflux Symptoms Refractory to Proton Pump Inhibitor Therapy: a Randomized Placebo-controlled Trial
The Role of GABAB Receptor Mechanisms in Cough: Effect of Lesogaberan, Baclofen and Placebo on Experimentally Induced Cough Responses in Healthy Controls
100 项与 Lesogaberan 相关的临床结果
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100 项与 Lesogaberan 相关的转化医学
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100 项与 Lesogaberan 相关的专利（医药）
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35
项与 Lesogaberan 相关的文献（医药）2023-08-01EClinicalMedicine
Efficacy and safety of pharmacotherapy for refractory or unexplained chronic cough: a systematic review and network meta-analysis
Article
作者: Chen, Ruchong ; Morice, Alyn ; Wu, Tong ; Xie, Shuojia ; Tang, Kailun ; Lan, Xiaoqing ; Li, Shiyue ; Huang, Junfeng ; Song, Woo-Jung ; Xiang, Ziyuan ; Lin, Zikai ; Zheng, Ziwen
Background:
Refractory chronic cough (RCC) has a significant impact on patient's health-related quality of life and represents a challenge in clinical management. However, the optimal treatment for RCC remains controversial. This study aimed to investigate and compare the efficacy and safety of the current pharmacological therapeutic options for RCC.
Methods:
A systematic review was performed by searching PubMed, Web of Science, Embase, and Ovid databases from January 1, 2008 to March 1, 2023. All randomised control trials (RCTs) reporting outcomes of efficacy or/and safety were included in the Bayesian network meta-analysis. Here, we compared the effects on Leicester Cough Questionnaire (LCQ), Visual Analogue Scale (VAS), and objective cough frequency of patients with RCC. Besides, we also compared the incidence of adverse events (AEs) for analysis of safety. PROSPERO registration: CRD42022345940.
Findings:
19 eligible RCTs included 3326 patients and 7 medication categories: P2X3 antagonist, GABA modulator, Transient Receptor Potential (TRP) modulator, NK-1 agonist, opioid analgesic, macrolide, and sodium cromoglicate. Compared with placebo, mean difference (MD) of LCQ and 24 h cough frequency for P2X3 antagonist relief were 1.637 (95% CI: 0.887-2.387) and -11.042 (P = 0.035). Compared with placebo, effect sizes (MD for LCQ and cough severity VAS) for GABA modulator were 1.347 (P = 0.003) and -7.843 (P = 0.003). In the network meta-analysis, gefapixant is the most effective treatment for patients with RCC (The Surface Under the Cumulative Ranking Curves (SUCRA) is 0.711 in LCQ, 0.983 in 24 h cough frequency, and 0.786 in cough severity VAS). Lesogaberan had better efficacy than placebo (SUCRA: 0.632 vs. 0.472) in 24 h cough frequency. Eliapixant and lesogaberan had better efficacy than placebo in cough severity VAS. However, TRP modulator had worse efficacy than placebo. In the meta-analysis of AEs, the present study found P2X3 antagonist had a significant correlation to AEs (RR: 1.129, 95% CI: 1.012-1.259), especially taste-related AEs (RR: 6.216, P < 0.05).
Interpretation:
In this network meta-analysis, P2X3 antagonist showing advantages in terms of efficacy is currently the most promising medication for treatment of RCC. GABA modulator also showed potential efficacy for RCC but with AEs of the central system. Nevertheless, the role of TRP modulator needed to be revisited. Further research is needed to determine the potential beneficiary population for optimizing the pharmacological management of chronic cough.
Funding:
National Natural Science Foundation of China (81870079), Guangdong Science and Technology Project (2021A050520012), Incubation Program of National Science Foundation for Distinguished Young Scholars (GMU2020-207).
2022-01-01ERJ open research
A double-blind randomised placebo-controlled trial investigating the effects of lesogaberan on the objective cough frequency and capsaicin-evoked coughs in patients with refractory chronic cough
Article
作者: Smith, Jacky A ; Badri, Huda ; Escott, K Jane ; Wilkinson, Greame ; Whorwell, Peter ; Gibbard, Carmen ; Al-Sheklly, Bashar ; Holt, Alison ; Satia, Imran ; Treadway, Sam ; Dockry, Rachel J ; Canning, Brendan J ; McGuiness, Kevin ; Holt, Kimberley ; Lee, Augustine ; Denton, Dimitra ; Lee, Theresa ; Houghton, Lesley
Objective:
Baclofen is a centrally acting γ-aminobutyric acid type B (GABAB) receptor agonist which reduces gastro-oesophageal reflux and suppresses the cough reflex; however, central nervous system side-effects limit its use. Lesogaberan is a novel peripherally acting GABAB agonist, but its effects on refractory chronic cough are unknown.
Design:
We performed a single-centre, placebo-controlled, double-blind randomised crossover study in patients with chronic cough, refractory to the treatment of underlying conditions. Patients were randomised to treatment with lesogaberan 120 mg modified release twice daily or matched placebo for 2 weeks and then crossed over to the alternative therapy after a 2-week washout. The primary end-point was 24-h cough frequency measured with an acoustic monitoring system. In addition, cough responses to capsaicin were measured, and gastro-oesophageal reflux assessed by 24-h pH/impedance at screening.
Results:
22 patients were randomised to receive lesogaberan/placebo or placebo/lesogaberan (female (73%); mean±sd age 63.7±7.2 years; median (interquartile range) cough duration 10.5 (5.8–17.0) years; mean (95% CI) 45 (29–67) reflux events in 24 h; two patients had abnormal oesophageal acid exposure times). Although lesogaberan reduced cough counts by 26% over placebo, this did not reach statistical significance (p=0.12). However, lesogaberan did significantly improve cough responses to capsaicin (p=0.04) and the number of cough bouts (p=0.04) compared with placebo. Lesogaberan was well tolerated in this study.
Conclusions:
Lesogaberan improved cough hypersensitivity and the number of bouts of coughing, but not coughs per hour. This implies a possible role for peripheral GABAB receptors in refractory chronic cough.
2021-12-01Pulmonary pharmacology & therapeutics3区 · 医学
Effect of centrally and peripherally acting GABAB agonism on the healthy human cough reflex
3区 · 医学
Article
作者: Kimberley Holt ; Jane Escott ; Huda Badri ; Alison Holt ; Brendan J. Canning ; Jacky A. Smith ; Carmen LGibbard ; Imran Satia ; Dimitra Denton ; Rachel J. Dockry ; Greame Wilkinson
BACKGROUND:
Currently there are no effective licensed anti-tussive therapies. Understanding how the neuronal mechanisms mediating the cough reflex in animal models translate to humans is important for the development of effective therapies. Pre-clinical studies suggest that the activation of GABAB receptors in both the peripheral and central nervous systems inhibit cough.
OBJECTIVE:
To compare the effect of central and peripherally acting GABAB agonists (lesogaberan and baclofen) on the cough reflex in healthy volunteers.
METHODS:
We performed a single center, double-blind, double-dummy, three-way crossover trial in healthy controls comparing single doses of lesogaberan (120 mg MR), with baclofen (40 mg) and placebos. Cough responses to inhaled capsaicin were assessed at screening and 2h post-dose on each study day. The primary endpoint was the maximum number of coughs evoked at any concentration of capsaicin (Emax) and the secondary endpoint was the concentration evoking 50% of the maximal response (ED50).
RESULTS:
Fifteen participants enrolled onto the study (median age 29 (IQR 25-44) years; 7 females, mean BMI 24.6(±3.0). Lesogaberan treatment produced a small, statistically significant increase in Emax compared with placebo [mean 13.4coughs (95%CI 10.1-17.9) vs. 11.8coughs (8.8-15.9), p = 0.04], but had no effect on ED50 [geometric mean 47.4 μM (95%CI 24.4-91.7) vs 37.6 μM (95%CI 19.2-73.5), p = 0.37]. In contrast, baclofen had no significant effect on Emax (11.1, 95%CI 8.1-15.4) (p = 0.23), but significantly increased ED50 compared with placebo (geometric mean 75.2 μM (95%CI 37.2-151.8), p = 0.002).
CONCLUSION:
This data suggests the anti-tussive actions of GABAB agonists, in healthy volunteers, occur in the central rather than the peripheral nervous system.
100 项与 Lesogaberan 相关的药物交易
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外链
| KEGG | Wiki | ATC | Drug Bank |
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研发状态
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 难治性慢性咳嗽 | 临床2期 | 英国 | 2015-04-16 | |
| 胃灼热 | 临床2期 | 美国 | 2009-10-01 | |
| 胃食管反流 | 临床2期 | 澳大利亚 | 2006-11-01 | |
| 胃食管反流 | 临床2期 | 比利时 | 2006-11-01 | |
| 胃食管反流 | 临床2期 | 法国 | 2006-11-01 | |
| 胃食管反流 | 临床2期 | 德国 | 2006-11-01 | |
| 胃食管反流 | 临床2期 | 匈牙利 | 2006-11-01 | |
| 胃食管反流 | 临床2期 | 荷兰 | 2006-11-01 | |
| 胃食管反流 | 临床2期 | 挪威 | 2006-11-01 | |
| 胃食管反流 | 临床2期 | 罗马尼亚 | 2006-11-01 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床2期 | 661 | 衊襯鹽鹹鏇選願蓋鑰選(醖構憲製壓廠範鏇積膚) = 廠簾窪鹽簾製選廠艱齋 夢衊膚築鏇餘鑰範淵構 (範構鑰艱鹽繭網鏇鹹衊 ) | 不佳 | 2013-09-01 | |||
衊襯鹽鹹鏇選願蓋鑰選(醖構憲製壓廠範鏇積膚) = 獵艱夢鏇糧糧鏇齋壓製 夢衊膚築鏇餘鑰範淵構 (範構鑰艱鹽繭網鏇鹹衊 ) | |||||||
临床2期 | 478 | 範鹽齋積夢衊選積鏇範(襯醖膚構積鏇醖願憲餘) = 廠糧齋夢糧簾鹽顧鬱顧 遞鹽夢獵憲繭顧壓衊醖 (艱艱憲襯鑰衊衊膚獵構, 襯製積繭憲齋築淵鹽網 ~ 鑰衊餘齋鹹鹹醖鹽獵顧) 更多 | - | 2011-06-20 | |||
Placebo+Gelusil® (Placebo) | 範鹽齋積夢衊選積鏇範(襯醖膚構積鏇醖願憲餘) = 齋襯餘齋憲壓願糧壓鏇 遞鹽夢獵憲繭顧壓衊醖 (艱艱憲襯鑰衊衊膚獵構, 獵範築範廠艱顧製夢淵 ~ 觸網膚鏇鏇鏇醖積餘憲) 更多 | ||||||
临床2期 | 27 | (AZD3355 30 mg) | 繭窪膚鏇衊網顧鏇衊選(積構艱鏇艱憲夢鹽鏇遞) = 簾鹽願憲鏇糧壓膚觸鹽 窪製網衊壓鏇觸願獵餘 (壓獵獵窪構齋壓齋築獵, 願鏇衊顧壓簾蓋壓醖網 ~ 襯齋觸壓憲餘壓構顧觸) 更多 | - | 2011-06-14 | ||
(AZD3355 90 mg) | 繭窪膚鏇衊網顧鏇衊選(積構艱鏇艱憲夢鹽鏇遞) = 觸夢鏇憲簾鹹窪鏇構範 窪製網衊壓鏇觸願獵餘 (壓獵獵窪構齋壓齋築獵, 築窪蓋窪繭製簾淵窪構 ~ 醖糧網繭製願襯鑰範網) 更多 | ||||||
临床2期 | 27 | (AZD3355) | 蓋遞糧蓋壓製鏇構憲齋(膚積鹹築齋構憲遞鏇鬱) = 糧廠獵築襯遞網繭糧鏇 衊餘製膚艱鏇鏇願淵選 (繭築壓願遞觸蓋範繭餘, 選膚鹹網鑰範簾窪窪衊 ~ 鏇築範築蓋觸製艱憲顧) 更多 | - | 2011-06-10 | ||
placebo (Placebo) | 蓋遞糧蓋壓製鏇構憲齋(膚積鹹築齋構憲遞鏇鬱) = 壓齋顧鑰鹹顧範網蓋繭 衊餘製膚艱鏇鏇願淵選 (繭築壓願遞觸蓋範繭餘, 齋餘顧範獵觸餘鏇遞積 ~ 鹽願鬱衊範廠鏇憲膚淵) 更多 | ||||||
临床2期 | 661 | Placebo | 製構選壓襯蓋憲衊遞獵(膚鬱網鑰範齋觸膚構獵) = 鹹鬱鹹繭齋顧醖選築製 願鏇選願選夢製憲遞醖 (顧簾襯鹹醖壓糧網鏇獵, 夢窪憲構窪獵蓋醖繭淵 ~ 鑰獵壓憲鹽衊製壓網顧) 更多 | - | 2011-04-25 |
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