司替匹仑(Setipiprant) - 药物靶点：CRTH2_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Setipiprant (USAN/INN)

靶点

CRTH2

作用机制

CRTH2拮抗剂(前列腺素D2受体2拮抗剂)

治疗领域

免疫系统疾病感染耳鼻咽喉疾病+ [2]

在研适应症-

非在研适应症

雄激素脱发哮喘季节性过敏性鼻炎

原研机构

Moon Collider Ltd.

Actelion Pharmaceuticals Ltd.

在研机构-

非在研机构

Actelion Pharmaceuticals Ltd.

Moon Collider Ltd.Allergan Ltd. (Ireland)

最高研发阶段终止临床3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/序列

分子式C24H19FN2O3

InChIKeyIHAXLPDVOWLUOS-UHFFFAOYSA-N

CAS号866460-33-5

关联

7

项与司替匹仑相关的临床试验

NCT02781311

/ Completed临床2期

Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2A Study of Setipiprant Tablets in Androgenetic Alopecia in Males

This study will evaluate the safety, tolerability and efficacy of the oral administration of setipiprant tablets 1000 mg twice daily (BID) relative to placebo in 18 to 49 years old males with androgenetic alopecia (AGA).

开始日期2016-07-14

申办/合作机构

Allergan Ltd. (Ireland)

NCT01484119

/ Completed临床3期

Multi-center, Double-blind, Double-dummy, Randomized, Placebo-controlled, Active-reference, Parallel-group Study to Evaluate the Efficacy, Safety, and Tolerability of ACT-129968 in Adolescent, Adult & Elderly Patients With Seasonal Allergic Rhinitis

This study will assess the efficacy and safety of ACT-129968 in adolescent, adult and elderly patients with seasonal allergic rhinitis, due to mountain cedar pollen.

开始日期2011-12-01

申办/合作机构

Idorsia Pharmaceuticals Ltd.

NCT02381496

/ Completed临床1期

A Three-part Study to Assess the Tolerability, Safety, Pharmacodynamics, and Pharmacokinetics of Ascending Single Doses (Including Food Interaction) of ACT-453859 in Healthy Male Subjects, of Ascending Multiple Doses of ACT-453859 in Healthy Male and Female Subjects, and of Multiple Doses of Setipiprant (ACT-129968) in Healthy Male and Female Subjects

This is a three-part study to assess the tolerability, safety, pharmacodynamics, and pharmacokinetics of ascending single doses (including food interaction) of ACT-453859 in healthy male subjects, of ascending multiple doses of ACT-453859 in healthy male and female subjects, and of multiple doses of setipiprant (ACT-129968) in healthy male and female subjects.

开始日期2011-12-01

申办/合作机构

Idorsia Pharmaceuticals Ltd.

100 项与司替匹仑相关的临床结果

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100 项与司替匹仑相关的转化医学

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100 项与司替匹仑相关的专利（医药）

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13

项与司替匹仑相关的文献（医药）

2017-12-01·Allergy, Asthma & Clinical Immunology4区 · 医学

Efficacy and safety of setipiprant in seasonal allergic rhinitis: results from Phase 2 and Phase 3 randomized, double-blind, placebo- and active-referenced studies

4区 · 医学

ArticleOA

作者: Mohar, Dale E ; Andrews, Charles P ; van Bavel, Jay ; Bourrelly, Denis ; Hampel, Frank C ; Mangialaio, Sara ; Ratner, Paul ; Martin, Bruce ; Hmissi, Abdel ; Dingemanse, Jasper ; Danaietash, Parisa

AbstractBackgroundAntagonism of chemoattractant receptor-homologous molecule on T-helper type-2 cells (CRTH2), a G-protein coupled receptor for prostaglandin D2, could be beneficial for treating allergic disorders. We present findings on the efficacy and safety/tolerability of a CRTH2 antagonist (setipiprant) in participants with seasonal allergic rhinitis (AR) in a real-life setting over 2 weeks.MethodsA Phase 2 trial and a Phase 3 trial were conducted at seven centers in Texas, USA during the Mountain Cedar pollen season. Both were prospective, randomized, double-blind, placebo- and active-referenced (cetirizine) studies. The Phase 2 trial assessed setipiprant 100–1000 mg b.i.d. and 1000 mg o.d. versus placebo in adult and elderly participants. The Phase 3 trial assessed setipiprant 1000 mg b.i.d. in adolescent, adult, and elderly participants. Efficacy was assessed using daytime nasal symptom scores (DNSS), night-time nasal symptom scores (NNSS) and daytime eye symptom scores (DESS).Results579 participants were randomized in the Phase 2 trial (mean age 41.6–43.4 years); 630 were randomized in the Phase 3 trial (mean age 37.5–40.7 years). A statistically significant, dose-related improvement in mean change from baseline DNSS was observed over 2 weeks with setipiprant 1000 mg b.i.d. versus placebo in the Phase 2 trial (−0.15 [95% CI −0.29, −0.01]; p = 0.030). Setipiprant 1000 mg b.i.d. had no significant effect on this endpoint in the Phase 3 trial (−0.02 [95% CI −0.12, 0.07]; p = 0.652). Total and individual NNSS and DESS symptom scores were significantly improved with setipiprant 1000 mg b.i.d. versus placebo in the Phase 2 but not the Phase 3 trial. Setipiprant showed a favorable safety/tolerability profile.ConclusionsThe Phase 2 trial was the first large clinical study to assess a CRTH2 antagonist in seasonal AR in a real-life setting. Setipiprant dose-related efficacy in the Phase 2 trial was not confirmed during Phase 3. Setipiprant was well tolerated in both studies.Trial registrationNCT01241214 and NCT01484119

2017-08-31·Physiological Research

Does Inhibition of Aldose Reductase Contribute to the Anti-Inflammatory Action of Setipiprant?

Article

作者: Ballekova, J. ; Soltesova-Prnova, M. ; Stefek, M. ; Majekova, M.

The aim of this study was to investigate aldose reductase inhibitory action of setipiprant as a potential additional mechanism contributing to its anti-inflammatory action. Aldose reductase activity was determined by spectrophotometric measuring of NADPH consumption. Setipiprant was found to inhibit aldose reductase/NADPH-mediated reduction of 4-hydroxynonenal, 4-hydroxynonenal glutathione and prostaglandin H2 substrates, all relevant to the process of inflammation. Molecular modeling simulations into the aldose reductase inhibitor binding site revealed an interaction pattern of setipiprant. Considering multifactorial etiology of inflammatory pathologies, it is suggested that, in addition to the antagonizing prostaglandin D2 receptor, inhibition of aldose reductase may contribute to the reported anti-inflammatory action of setipiprant.

2017-08-01·Drugs1区 · 医学

Targeting the PGD2/CRTH2/DP1 Signaling Pathway in Asthma and Allergic Disease: Current Status and Future Perspectives

1区 · 医学

Review

作者: Kupczyk, Maciej ; Kuna, Piotr

Prostaglandin D₂ (PGD₂) released by degranulating mast cells is believed to play a key role in orchestrating mechanisms of inflammation in allergies and asthma. The biological effects of PGD₂ are mediated by D-prostanoid (DP1), CRTH2 (DP2), and thromboxane prostanoid (TP) receptors. The CRTH2 receptor is involved in induction of migration and activation of T helper type 2 (Th₂) lymphocytes, eosinophils, and basophils; up-regulation of adhesion molecules; and promotion of pro-inflammatory Th₂-type cytokines (interleukin [IL]-4, 5, 13), whereas the DP receptor is associated with relaxation of smooth muscles, vasodilation, inhibition of cell migration, and apoptosis of eosinophils. A number of CRTH2/PGD₂ receptor antagonists have been investigated in asthma and allergic diseases. The CRTH2 antagonist (OC000459) or dual CRTH2 and TP receptor antagonist (ramatroban) were effective in reducing eosinophilia, nasal mucosal swelling, and clinical symptoms of allergic rhinitis, with the latter drug registered for clinical use in this indication. OC000459 and setipiprant reduced the late but not early phase of response in an allergen challenge in atopic asthmatics. In persistent asthma, some molecules induced limited improvement in lung function, quality of life, and asthma symptoms (OC000459, BI671800), but in other trials with AMG 853 and AZ1981 these findings were not confirmed. The clear discrepancy between animal studies and clinical efficacy of CRTH2 antagonism in allergic rhinitis, and lack of efficacy in a general cohort of asthmatics, highlight the issue of patient phenotyping. There is no doubt that the PGD₂/CATH2/DP1 pathway plays a key role in allergic inflammation and further studies with selective or combined antagonisms in well defined cohorts of patients are needed.

100 项与司替匹仑相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10326	司替匹仑	-	DB12562

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
哮喘	临床3期	南非	Actelion Pharmaceuticals Ltd.	-
哮喘	临床3期	塞尔维亚	Actelion Pharmaceuticals Ltd.	-
哮喘	临床3期	澳大利亚	Actelion Pharmaceuticals Ltd.	-
哮喘	临床3期	波兰	Actelion Pharmaceuticals Ltd.	-
哮喘	临床3期	以色列	Actelion Pharmaceuticals Ltd.	-
哮喘	临床3期	德国	Actelion Pharmaceuticals Ltd.	-
哮喘	临床3期	匈牙利	Actelion Pharmaceuticals Ltd.	-
哮喘	临床3期	乌克兰	Actelion Pharmaceuticals Ltd.	-
季节性过敏性鼻炎	临床3期	-	Moon Collider Ltd.	-
季节性过敏性鼻炎	临床3期	美国	Actelion Pharmaceuticals Ltd.	-

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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


NCT02781311 (CTgov)	临床2期	雄激素脱发	169	Placebo (Placebo)	簾壓製齋簾築淵夢顧蓋(範選壓壓窪壓觸壓壓選) = 夢餘膚遞鬱願顧鏇鹽繭淵窪鹽淵鑰網衊網觸艱 (鬱鹹淵襯憲築願膚鏇鹹, 顧繭憲鹽網遞網築夢窪 ~ 製淵廠築餘獵醖窪範齋) 更多	-	2019-04-05
				Setipiprant (Setipiprant)	簾壓製齋簾築淵夢顧蓋(範選壓壓窪壓觸壓壓選) = 鬱顧窪製鹽鹹襯鏇願簾淵窪鹽淵鑰網衊網觸艱 (鬱鹹淵襯憲築願膚鏇鹹, 鏇鏇選鹹構艱壓夢範構 ~ 艱繭艱蓋選膚觸簾蓋艱) 更多
NCT01241214 (Pubmed \| Allergy Asthma Clin Immunol) 人工标引	临床2/3期	季节性过敏性鼻炎	579	setipiprant	(淵簾膚鏇築窪襯淵壓鹽): difference = -0.15 (95% CI, -0.29 ~ -0.01), P-Value = 0.030	积极	2017-04-04
				Placebo