CX-157(CX-157) - 药物靶点：MAO-A_专利_临床

概要

基本信息

药物类型

小分子化药

别名

TriRima、Tyrima

+ [3]

靶点

MAO-A

作用机制

MAO-A抑制剂(单胺氧化酶A抑制剂)

治疗领域

其他疾病

在研适应症-

非在研适应症

焦虑症抑郁症重度抑郁症+ [1]

原研机构

Krenitsky Pharmaceuticals, Inc.

在研机构-

非在研机构

CeNeRx BioPharma, Inc.

Krenitsky Pharmaceuticals, Inc.

最高研发阶段终止临床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C14H8F4O4S

InChIKeyPDIMOTRDGUQMNY-UHFFFAOYSA-N

CAS号205187-53-7

关联

3

项与 CX-157 相关的临床试验

NCT01246908 / Completed临床2期

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Assessment of the Efficacy, Safety and Tolerability of CX157 Modified Release Tablet, 125 mg Twice Per Day in Subjects With Treatment Resistant Depression

The purpose of this study is to determine if CX157 is effective and safe in patients with treatment of treatment resistant depression over six weeks of treatment.

开始日期2010-11-01

申办/合作机构

CeNeRx BioPharma, Inc.

NCT01633437 / Completed临床1期

A Phase I, Multiple-Dose, Randomized, Double-Blind, Oral Tyramine Pressor Response Study Comparing CX157 Tablets to Placebo in Healthy Male Volunteers

The objectives of this study were to examine the cardiovascular sensitivity to oral tyramine after establishment of steady state with CX157 Modified Release (MR) Tablets, 125 mg administered twice per day (BID) in healthy volunteers compared to placebo; and to investigate the general safety, tolerability and pharmacokinetic profile of CX157 tablets at steady state compared to placebo.

开始日期2010-09-01

申办/合作机构

CeNeRx BioPharma, Inc.

NCT00739908 / Completed临床2期

A Randomized, Double-Blind, Placebo-Controlled Parallel-Group, Assessment of the Efficacy, Safety and Tolerability of CX157 (TriRima) 60mg Three Times a Day (TID) in Subjects With Major Depressive Disorder

The purpose of this study is to examine the efficacy of CX157 60 mg administered three times a day (180 mg daily dose) as compared to placebo in subjects with Major Depressive Disorder (MDD). Secondary objectives are to evaluate the safety and tolerability and steady state pharmacokinetic profile of CX157 in these subjects.

开始日期2008-09-01

申办/合作机构

CeNeRx BioPharma, Inc.

100 项与 CX-157 相关的临床结果

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100 项与 CX-157 相关的转化医学

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100 项与 CX-157 相关的专利（医药）

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3

项与 CX-157 相关的文献（医药）

2017-12-01·Journal of Psychiatric Research2区 · 医学

Early symptomatic improvement affects treatment outcome in a study of major depressive disorder

2区 · 医学

Article

作者: Targum, Steven D

Early symptomatic improvement immediately following randomization can affect signal detection in clinical trials. The impact of early improvement of the Montgomery-Asberg depression rating scale (MADRS) on eventual treatment outcome was examined in a 6-week, double-blind, placebo-controlled trial of a putative antidepressant (CX157) versus placebo in depressed subjects with major depressive disorder (MDD) who had had an inadequate response to ongoing antidepressant treatment (NCT00739908). MADRS score changes within one week after randomization directly affected treatment outcome at the study endpoint (week 6). The response and remission rates at week 6 increased significantly as the percent of MADRS score improvement increased between baseline and week 1 regardless of treatment assignment. Less MADRS improvement or actual worsening within the first week after randomization was associated with minimal overall MADRS score changes by week 6 in either treatment assignment. Alternatively, CX157 assigned subjects who had ≥30% improvement by week 1 achieved a significantly greater treatment response rate than the matched placebo group at the study endpoint (p = 0.025) that converted the lack of signal detection in the mITT population. This post-hoc analysis highlights the potent effect that early symptomatic improvement immediately following randomization can have on treatment outcome, and is particularly relevant for antidepressant drugs with rapid onset of action. The findings compel further exploration of possible moderating and mediating factors, including the experimental condition itself that can influence early response, and the need to identify "bio-types" within the population of MDD subjects.

2014-01-01·Clinical Pharmacology in Drug Development4区 · 医学

Lack of tyramine pressor response effect with oral CX157: A specific reversible MAOI

4区 · 医学

Article

作者: Asgharnejad, Mahnaz ; Fielding, Robert M. ; Gerson, William ; Azzaro, Albert J. ; Burch, Daniel

AbstractThis Phase 1, single‐center, double‐blind, placebo‐controlled, three‐period study assessed cardiovascular safety of CX157, a specific Reversible Inhibitor of Monoamine Oxidase A (RIMA), following the oral administration of tyramine. In Period 1, the sensitivity of each subject to orally administered tyramine was established by determining the dose of tyramine that elevates SBP ≥30 mmHg on ≥3 consecutive occasions (i.e., TYR303). Twelve subjects qualified for randomization in Period 2 during which an oral CX157 Modified Release Tablet (125 mg [N = 10]) or placebo (N = 2) were administered twice per day for 6 days to reach steady state. In Period 3, CX157 and placebo were administered with oral tyramine in fed state with daily increases in the tyramine dose of 20, 40, and 80 mg in an attempt to achieve the TYR303. CX157 Modified Release Tablet, 125 mg administered twice per day (250 mg daily dose), was not associated with a tyramine reaction (i.e., TYR303). It is generally agreed that a high tyramine meal would contain up to 40 mg of dietary tyramine. These data obtained with CX157 provide an adequate margin of safety with respect to tyramine interaction and suggest that future studies can be conducted without the need for dietary tyramine restrictions.

2010-02-01·Neuropsychopharmacology1区 · 医学

Reversible Inhibitors of Monoamine Oxidase-A (RIMAs): Robust, Reversible Inhibition of Human Brain MAO-A by CX157

1区 · 医学

Article

作者: Daniel Burch ; Albert J Azzaro ; David Alexoff ; Colleen Shea ; Payton King ; Mahnaz Asgharnejad ; Barbara Hubbard ; Joanna S Fowler ; Pauline Carter ; Karen Apelskog-Torres ; Robert M Fielding ; Gene-Jack Wang ; Donald Warner ; Elena Shumay ; James Free ; Michael Schueller ; Lisa Muench ; Millard Jayne ; Barry Brand ; Amy K Poshusta ; Wei Zhu ; Frank Telang ; Scott Carter ; Youwen Xu ; Jean Logan

Reversible inhibitors of monoamine oxidase-A (RIMA) inhibit the breakdown of three major neurotransmitters, serotonin, norepinephrine and dopamine, offering a multi-neurotransmitter strategy for the treatment of depression. CX157 (3-fluoro-7-(2,2,2-trifluoroethoxy)phenoxathiin-10,10-dioxide) is a RIMA, which is currently in development for the treatment of major depressive disorder. We examined the degree and reversibility of the inhibition of brain monoamine oxidase-A (MAO-A) and plasma CX157 levels at different times after oral dosing to establish a dosing paradigm for future clinical efficacy studies, and to determine whether plasma CX157 levels reflect the degree of brain MAO-A inhibition. Brain MAO-A levels were measured with positron emission tomography (PET) imaging and [(11)C]clorgyline in 15 normal men after oral dosing of CX157 (20-80 mg). PET imaging was conducted after single and repeated doses of CX157 over a 24-h time course. We found that 60 and 80 mg doses of CX157 produced a robust dose-related inhibition (47-72%) of [(11)C]clorgyline binding to brain MAO-A at 2 h after administration and that brain MAO-A recovered completely by 24 h post drug. Plasma CX157 concentration was highly correlated with the inhibition of brain MAO-A (EC(50): 19.3 ng/ml). Thus, CX157 is the first agent in the RIMA class with documented reversible inhibition of human brain MAO-A, supporting its classification as a RIMA, and the first RIMA with observed plasma levels that can serve as a biomarker for the degree of brain MAO-A inhibition. These data were used to establish the dosing regimen for a current clinical efficacy trial with CX157.

100 项与 CX-157 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	CX-157	-	DB05205

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
难治性抑郁症	临床2期	美国	CeNeRx BioPharma, Inc.	2010-11-01
重度抑郁症	临床2期	美国	CeNeRx BioPharma, Inc.	2008-09-01
焦虑症	临床2期	-	Krenitsky Pharmaceuticals, Inc.	-
焦虑症	临床2期	-	CeNeRx BioPharma, Inc.	-
抑郁症	临床2期	-	Krenitsky Pharmaceuticals, Inc.	-

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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


NCT00739908 (CX157-200, CTgov)	临床2期	重度抑郁症	285	CX157 (Oral CX157 60 mg TID (Total Daily Dose of 180 mg))	積築構構鑰選廠選顧蓋(壓膚糧構鹹範簾齋積鏇) = 簾遞網窪遞網憲夢觸願淵餘窪獵窪餘遞製鬱醖 (壓餘醖鹹鹹膚夢鑰蓋蓋, 糧顧蓋願廠選觸顧鑰觸 ~ 積鏇鬱築廠簾廠鏇齋製) 更多	-	2012-06-27
				Placebo (Oral Placebo TID)	積築構構鑰選廠選顧蓋(壓膚糧構鹹範簾齋積鏇) = 廠淵齋顧鹹壓鏇築築糧淵餘窪獵窪餘遞製鬱醖 (壓餘醖鹹鹹膚夢鑰蓋蓋, 鹹憲築範壓顧餘襯獵淵 ~ 鹽顧鬱簾窪鹽壓鹽觸憲) 更多