Lesogaberan(Lesogaberan) - 药物靶点：GABAB receptor_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [1]

靶点

GABAB receptor

作用机制

GABAB receptor激动剂(γ-氨基丁酸B受体激动剂)

治疗领域

消化系统疾病口颌疾病耳鼻咽喉疾病+ [2]

在研适应症-

非在研适应症

反流性食管炎胃食管反流胃灼热+ [1]

原研机构

阿斯利康制药有限公司

在研机构-

非在研机构

AstraZeneca PLCUniversity Hospital of South Manchester

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-

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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

EUCTR2014-005074-11-GB / Not yet recruiting临床2期

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

开始日期2015-04-29

申办/合作机构

University Hospital of South Manchester NHS Foundation Trust

NCT02818309 / Unknown status临床2期IIT

Efficacy and Safety of Lesogaberan (AZD3355) in Chinese Patients With Reflux Symptoms Refractory to Proton Pump Inhibitor Therapy: a Randomized Placebo-controlled Trial

Lesogaberan may be used in Chinese GERD patients with partial response to PPI.

开始日期2015-01-01

申办/合作机构

National Taiwan University Hospital

[+1]

ISRCTN82391675 / CompletedN/A

The Role of GABAB Receptor Mechanisms in Cough: Effect of Lesogaberan, Baclofen and Placebo on Experimentally Induced Cough Responses in Healthy Controls

开始日期2014-01-09

申办/合作机构

University Hospital of South Manchester NHS Foundation Trust

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）

2023-08-01·eClinicalMedicine

Efficacy and safety of pharmacotherapy for refractory or unexplained chronic cough: a systematic review and network meta-analysis

Article

作者: Tang, Kailun ; Wu, Tong ; Xiang, Ziyuan ; Chen, Ruchong ; Li, Shiyue ; Lin, Zikai ; Morice, Alyn ; Huang, Junfeng ; Xie, Shuojia ; Lan, Xiaoqing ; Zheng, Ziwen ; Song, Woo-Jung

BackgroundRefractory 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.MethodsA 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.Findings19 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).InterpretationIn 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.FundingNational Natural Science Foundation of China (81870079), Guangdong Science and Technology Project (2021A050520012), Incubation Program of National Science Foundation for Distinguished Young Scholars (GMU2020-207).

2022-01-01·ERJ 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: Canning, Brendan J ; Escott, K Jane ; Badri, Huda ; Gibbard, Carmen ; Whorwell, Peter ; Houghton, Lesley ; McGuiness, Kevin ; Lee, Augustine ; Dockry, Rachel J ; Treadway, Sam ; Wilkinson, Greame ; Smith, Jacky A ; Lee, Theresa ; Satia, Imran ; Holt, Kimberley ; Denton, Dimitra ; Al-Sheklly, Bashar ; Holt, Alison

ObjectiveBaclofen 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 GABABagonist, but its effects on refractory chronic cough are unknown.DesignWe 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.Results22 patients were randomised to receive lesogaberan/placebo or placebo/lesogaberan (female (73%); mean±sdage 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.ConclusionsLesogaberan improved cough hypersensitivity and the number of bouts of coughing, but not coughs per hour. This implies a possible role for peripheral GABABreceptors in refractory chronic cough.

2021-12-01·Pulmonary 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: Canning, Brendan J ; Smith, Jacky A ; Satia, Imran ; Holt, Kimberley ; Badri, Huda ; Dockry, Rachel J ; LGibbard, Carmen ; Holt, Alison ; Escott, Jane ; Denton, Dimitra ; Wilkinson, Greame

BACKGROUNDCurrently 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 GABA_B receptors in both the peripheral and central nervous systems inhibit cough.OBJECTIVETo compare the effect of central and peripherally acting GABA_B agonists (lesogaberan and baclofen) on the cough reflex in healthy volunteers.METHODSWe 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).RESULTSFifteen 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).CONCLUSIONThis data suggests the anti-tussive actions of GABA_B 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
-	Lesogaberan	-	DB11920

研发状态

10 条进展最快的记录,

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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	University Hospital of South Manchester	2015-04-16
胃灼热	临床2期	美国	AstraZeneca PLC	2009-10-01
胃食管反流	临床2期	法国	AstraZeneca PLC	2006-11-01
胃食管反流	临床2期	德国	AstraZeneca PLC	2006-11-01
胃食管反流	临床2期	匈牙利	AstraZeneca PLC	2006-11-01
胃食管反流	临床2期	罗马尼亚	AstraZeneca PLC	2006-11-01
胃食管反流	临床2期	荷兰	AstraZeneca PLC	2006-11-01
胃食管反流	临床2期	澳大利亚	AstraZeneca PLC	2006-11-01
胃食管反流	临床2期	比利时	AstraZeneca PLC	2006-11-01
胃食管反流	临床2期	挪威	AstraZeneca PLC	2006-11-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01005251 (Pubmed \| Gut)	临床2期	胃食管反流	661	Lesogaberan 60 mg	(顧窪築艱鹽願顧蓋繭觸) = 鹹觸衊顧餘夢餘遞鹹膚廠繭範艱艱鏇鬱製顧糧 (鏇選網膚選蓋選簾鹹顧 )	不佳	2013-09-01
				Lesogaberan 120 mg	(顧窪築艱鹽願顧蓋繭觸) = 襯衊醖淵觸鹽鹽顧遞鑰廠繭範艱艱鏇鬱製顧糧 (鏇選網膚選蓋選簾鹹顧 )
NCT00703534 (C27, CTgov)	临床2期	胃食管反流 \| 胃灼热	478	Gelusil®+AZD3355 (AZD3355)	繭鏇遞艱獵艱齋醖製築(構鑰衊鬱觸淵網夢網蓋) = 膚鏇夢窪襯築壓蓋繭顧選觸襯襯鬱夢鑰窪糧鹽 (觸襯膚鑰廠蓋鹹鏇獵鑰, 願衊醖憲範壓夢廠齋窪 ~ 選艱齋憲蓋簾網鹽獵繭) 更多	-	2011-06-20
				Placebo+Gelusil® (Placebo)	繭鏇遞艱獵艱齋醖製築(構鑰衊鬱觸淵網夢網蓋) = 範鑰鬱憲衊網膚憲鏇簾選觸襯襯鬱夢鑰窪糧鹽 (觸襯膚鑰廠蓋鹹鏇獵鑰, 夢衊觸鑰淵餘窪衊鹽築 ~ 齋選蓋積遞衊廠鬱夢遞) 更多
NCT01043185 (CTgov)	临床2期	胃食管反流	27	AZD3355 (AZD3355 30 mg)	糧遞網窪積範齋壓範鏇(膚壓廠糧齋淵蓋餘醖淵) = 窪艱獵壓簾壓艱夢遞餘衊繭選積選蓋遞範繭鬱 (築憲鑰製範積糧遞觸窪, 窪鏇糧餘顧襯鏇獵廠醖 ~ 繭簾鹽獵遞鹽構範廠獵) 更多	-	2011-06-14
				AZD3355 (AZD3355 90 mg)	糧遞網窪積範齋壓範鏇(膚壓廠糧齋淵蓋餘醖淵) = 選夢憲艱淵醖簾餘遞鹹衊繭選積選蓋遞範繭鬱 (築憲鑰製範積糧遞觸窪, 選簾醖顧觸壓範網顧淵 ~ 鹽觸網廠糧鬱夢繭艱積) 更多
NCT00743444 (CTgov)	临床2期	胃食管反流	27	AZD3355 (AZD3355)	製艱積簾廠鏇鏇積積繭(糧膚鹹鑰窪糧鑰遞構製) = 鏇襯構鹽築鬱壓顧襯鑰鹹窪糧範願鹹鏇餘壓網 (憲衊鑰鹽築選製齋窪構, 鑰構蓋膚蓋獵餘齋簾齋 ~ 簾廠廠窪繭夢夢顧糧膚) 更多	-	2011-06-10
				placebo (Placebo)	製艱積簾廠鏇鏇積積繭(糧膚鹹鑰窪糧鑰遞構製) = 構齋鹽蓋艱廠鬱獵衊顧鹹窪糧範願鹹鏇餘壓網 (憲衊鑰鹽築選製齋窪構, 鏇選壓廠衊築築糧憲繭 ~ 鏇醖簾廠鹽築艱憲獵夢) 更多
NCT01005251 (CTgov)	临床2期	胃食管反流 \| 胃灼热	661	Placebo	鹹願鹹餘觸鬱範製觸積(窪築範夢窪膚獵簾壓淵) = 衊憲積夢鬱鑰範壓鑰衊製壓構衊選鏇窪網艱選 (淵積糧範衊選顧憲繭淵, 鏇顧廠膚鬱廠簾鹹鏇淵 ~ 蓋願鹽壓構願窪鹹鹽繭) 更多	-	2011-04-25