Velusetrag(Velusetrag) - 药物靶点：5-HT4 receptor_在研适应症：假性肠梗阻_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Velusetrag (USAN/INN)、Velusetrag Hydrochloride

靶点

5-HT4 receptor

作用方式

激动剂

作用机制

5-HT4 receptor激动剂(5-羟色胺受体4激动剂)

治疗领域

消化系统疾病

在研适应症

假性肠梗阻

非在研适应症

阿尔茨海默症慢性便秘糖尿病性胃轻瘫+ [1]

原研机构

Theravance Biopharma, Inc.

在研机构

Alfasigma SpA

非在研机构

Theravance Biopharma, Inc.

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评孤儿药 (欧盟)

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结构/序列

分子式C25H36N4O5S

InChIKeyHXLOHDZQBKCUCR-WOZUAGRISA-N

CAS号866933-46-2

关联

7

项与 Velusetrag 相关的临床试验

CTIS2024-513988-70-00

/ Recruiting临床1期

- VE-CIP1002/2021

开始日期2024-10-07

申办/合作机构

Alfasigma SpA

EUCTR2021-000854-24-BE

/ Not yet recruiting临床2期

Velusetrag for the treatment of Chronic Intestinal Pseudo-Obstruction (CIPO). A multicenter double-blind, placebo-controlled, cross-over, multiple (n=1) trial. - N/A

开始日期2022-04-27

申办/合作机构

Alfasigma SpA

NCT05724069

/ Active, not recruiting临床2期

Velusetrag for the Treatment of Chronic Intestinal Pseudo-Obstruction (CIPO). A Multicenter, Double-blind, Placebo-controlled, Cross-over, Multiple (n=1) Trial.

This is a phase II, multicenter, double-blind, placebo-controlled trial to evaluate the efficacy and safety of velusetrag once a day, compared to placebo, in subjects with CIPO.

开始日期2021-12-15

申办/合作机构

Alfasigma SpA

100 项与 Velusetrag 相关的临床结果

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100 项与 Velusetrag 相关的转化医学

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100 项与 Velusetrag 相关的专利（医药）

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43

项与 Velusetrag 相关的文献（医药）

2024-01-08·Cureus

Safety and Efficacy of Highly Selective 5-Hydroxytryptamine Receptor 4 Agonists for Diabetic and Idiopathic Gastroparesis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Review

作者: Zaher, Eli A ; Khataniar, Himsikhar ; Ebrahim, Mohamed A ; Loganathan, Priyadarshini ; Patel, Parth

Gastroparesis significantly affects quality of life and healthcare expenditure. Effective treatment options are limited, and the utility of current prokinetic agents is inhibited by serious adverse effects. There exists an unmet need for prokinetic agents demonstrating both efficacy and an acceptable adverse effect profile. Highly selective 5-Hydroxytryptamine receptor 4 (5-HT4) agonists have exhibited clinical efficacy and safety in randomized controlled trials (RCTs). Consequently, we conducted a meta-analysis to comprehensively assess the safety and efficacy of these highly selective agents. Multiple databases, including PubMed, Scopus, and Embase, were systematically screened from inception until September 2023. Only RCTs evaluating the efficacy and safety of highly selective 5-HT4 agonists for gastroparesis were included. Key outcomes of interest included the pooled rates of Gastroparesis Cardinal Symptom Index (GCSI) scores, gastric emptying time (GET), and adverse event rates in each group. We adhered to standard meta-analysis methodology utilizing the random-effects model, with heterogeneity assessed by I² statistics. Our analysis identified six RCTs, comprising 570 patients with diabetic (48%) or idiopathic (51%) gastroparesis, with mean ages of 46 and 45.9 years in the intervention and placebo groups, respectively. In the meta-analysis, highly selective 5-HT4 agonists demonstrated significantly superior pooled GCSI scores compared to placebo (mean difference: 4.283, (1.380, 7.186), p<0.05). Pooled GET was also significantly improved with 5-HT4 agonists compared to placebo (mean difference: 2.534, (1.695, 3.373), p<0.05). Although pooled rates of total adverse events were higher with 5-HT4 agonists (mean difference: 6.975, (1.042, 46.684), p<0.05), rates of specific adverse events such as diarrhea, abdominal pain, and headaches were comparable. In conclusion, this meta-analysis underscores a statistically significant improvement in GET and GCSI scores among patients receiving highly selective 5-HT4 agonists (Velusetrag, Felcisetrag, Prucalopride) for both diabetic and idiopathic gastroparesis. While the overall adverse effect profile is deemed acceptable, larger studies with extended follow-up periods are needed to investigate rare and/or serious adverse events. Moreover, future high-quality RCTs comparing the efficacy and safety of these novel agents with currently available agents are essential to further validate these findings.

2023-04-01·Neurogastroenterology & Motility

A randomized, double‐blind, placebo‐controlled, phase 2b study of the efficacy and safety of velusetrag in subjects with diabetic or idiopathic gastroparesis

Article

作者: Grimaldi, Maria ; Abell, Thomas L. ; Barnes, Chris N. ; Kuo, Braden ; Nguyen, Deanna D. ; Tacchi, Raffaella ; McCallum, Richard ; Nguyen, Linda ; Esfandyari, Tuba ; Renzulli, Cecilia ; Zhou, Kefei ; Pfeifer, Nathan D. ; Talley, Nicholas J.

AbstractBackgroundThis study assessed the efficacy and safety of velusetrag—a 5‐HT4 agonist with pan‐gastrointestinal prokinetic activity—for gastroparesis symptom management and gastric emptying (GE).MethodsIn this multicenter, double‐blind, randomized, placebo‐controlled study, subjects with diabetic or idiopathic gastroparesis received velusetrag 5, 15, or 30 mg or placebo for 12 weeks. The primary efficacy outcome was a 7‐day mean Gastroparesis Cardinal Symptom Index 24‐h composite score (GCSI‐24H) change from baseline at week 4; GE was evaluated using scintigraphy (GES) and breath tests, and safety from adverse events (AEs).Key Results232 subjects (183 females; 113 idiopathic gastroparesis) received treatment from February 2015 through June 2017. Least‐squares mean improvement from baseline GCSI‐24H (primary endpoint) at week 4 was −1.5 following velusetrag 5 mg vs −1.1 following placebo (treatment difference, −0.4; 95% confidence interval, −0.75 to −0.03; nominal p = 0.0327; Hochberg‐adjusted p = 0.0980 [not significant]). Symptom improvement from baseline was achieved only with velusetrag 5 mg, which resulted in greater improvement from baseline vs placebo in all gastroparesis core symptoms, especially in subjects with idiopathic gastroparesis. Improvement from baseline GE by GES was greater in subjects receiving velusetrag (all doses) vs placebo; >70% of subjects receiving velusetrag 30 mg had GE normalization at 4 h. Treatment‐emergent AEs were generally mild.Conclusions and InferencesVelusetrag treatment was generally well‐tolerated and associated with improved GE vs placebo in subjects with diabetic or idiopathic gastroparesis; however, only the lowest dose, velusetrag 5 mg, was associated with short‐term improvement in gastroparesis symptoms.ClinicalTrials.govNCT02267525.

2022-12-12·Expert Opinion on Pharmacotherapy

Pharmacotherapeutic advances for chronic idiopathic constipation in adults

Article

作者: Berti, Ginevra ; Bellini, Massimo ; Villanacci, Vincenzo ; Lai, Mariantonia ; Bassotti, Gabrio ; Usai Satta, Paolo

INTRODUCTIONChronic idiopathic constipation is a common gastrointestinal disorder whose treatment is still far from being satisfactory for patients. Osmotic laxatives, in particular polyethylene glycol, are the first-line approach, but new emerging pharmacological agents may be useful in refractory patients.AREAS COVEREDPublished articles regarding the development and clinical efficacy of new agents in treating chronic idiopathic constipation were reviewed. Among emerging agents, elobixibat, a drug blocking the reabsorption of bile acids, is a promising one, especially in slow transit constipation. Linaclotide, lubiprostone and plecanatide, by a secretagogue action, improve stool consistency and increase colonic transit. Apart from prucalopride, approved in Europe for refractory chronic idiopathic constipation patients, the selective 5-HT4 agonists velusetrag and naronapride are in advanced development. In addition, relamorelin, a ghrelin agonist, seems promising for accelerating colonic transit.EXPERT OPINIONSeveral new promising drugs have been released with the potential to be effective in the treatment of chronic idiopathic constipation. On the other hand, the experience with these new agents is still limited, especially for long-term treatment. Another important point is that these new treatments for chronic idiopathic constipation are not available worldwide and their use could be somewhat limited by their still relatively high cost.

100 项与 Velusetrag 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09693	Velusetrag	-	DB12702

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
假性肠梗阻	临床2期	西班牙	Alfasigma SpA	2021-12-15
假性肠梗阻	临床2期	意大利	Alfasigma SpA	2021-12-15
假性肠梗阻	临床2期	比利时	Alfasigma SpA	2021-12-15
糖尿病性胃轻瘫	临床2期	-	Alfasigma SpA	2014-12-01
糖尿病性胃轻瘫	临床2期	-	Theravance Biopharma, Inc.	2014-12-01
胃轻瘫	临床2期	-	Alfasigma SpA	2014-12-01
胃轻瘫	临床2期	-	Theravance Biopharma, Inc.	2014-12-01
阿尔茨海默症	临床2期	美国	Theravance Biopharma, Inc.	2011-11-01
慢性便秘	临床2期	美国	Theravance Biopharma, Inc.	2006-10-01

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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


NCT02267525 (Corporate Publications) 人工标引	临床2期	胃轻瘫	232	TD-5108	(選遞簾廠繭構醖窪廠糧): P-Value = 0.0327 更多	积极	2017-08-02
				Placebo
VELUSETRAG (UEGW2015)	N/A	胃轻瘫 HbA1c	34	Velusetrag 5mg	鏇膚蓋餘鹽構鑰膚壓襯(繭鑰憲窪憲顧構鏇願壓) = n=16 餘範齋網製製夢蓋夢網 (選艱構襯網願壓糧積簾 ) 更多	积极	2015-10-01
				Velusetrag 15mg
NCT00391820 (Pubmed \| Aliment Pharmacol Ther)	临床2期	慢性特发性便秘	-	Placebo	鹽繭獵餘壓窪襯簾窪繭(壓淵衊壓顧鬱願衊積醖) = 製築願鏇遞廠願憲網鏇艱齋鹽觸鬱鏇鏇齋醖襯 (鏇鬱製醖獵糧鑰繭鑰齋 )	-	2010-11-01
				Velusetrag 15 mg	鹽繭獵餘壓窪襯簾窪繭(壓淵衊壓顧鬱願衊積醖) = 齋築艱鹽鬱鹽選鬱艱醖艱齋鹽觸鬱鏇鏇齋醖襯 (鏇鬱製醖獵糧鑰繭鑰齋 )