Delving into the Latest Updates on CX-157 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

TriRima, Tyrima

+ [3]

Target

MAO-A

Mechanism

MAO-A inhibitors(Monoamine oxidase A inhibitors)

Therapeutic Areas

Other Diseases

Active Indication-

Inactive Indication

Anxiety DisordersDepressive DisorderDepressive Disorder, Major+ [1]

Originator Organization

Krenitsky Pharmaceuticals, Inc.

Active Organization-

Inactive Organization

CeNeRx BioPharma, Inc.

Krenitsky Pharmaceuticals, Inc.

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC14H8F4O4S

InChIKeyPDIMOTRDGUQMNY-UHFFFAOYSA-N

CAS Registry205187-53-7

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.

Start Date01 Sep 2010

Sponsor / Collaborator

CeNeRx BioPharma, Inc.

NCT00739908 / CompletedPhase 2

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.

Start Date01 Sep 2008

Sponsor / Collaborator

CeNeRx BioPharma, Inc.

100 Clinical Results associated with CX-157

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100 Translational Medicine associated with CX-157

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100 Patents (Medical) associated with CX-157

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3

Literatures (Medical) associated with CX-157

01 Dec 2017·Journal of Psychiatric ResearchQ2 · MEDICINE

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

Q2 · MEDICINE

Article

Author: 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.

01 Jan 2014·Clinical Pharmacology in Drug DevelopmentQ4 · MEDICINE

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

Q4 · MEDICINE

Article

Author: 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.

01 Feb 2010·NeuropsychopharmacologyQ1 · MEDICINE

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

Q1 · MEDICINE

Article

Author: 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 Deals associated with CX-157

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External Link

KEGG	Wiki	ATC	Drug Bank
-	CX-157	-	DB05205

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Depressive Disorder, Treatment-Resistant	Phase 2	US	CeNeRx BioPharma, Inc.	01 Nov 2010
Depressive Disorder, Major	Phase 2	US	CeNeRx BioPharma, Inc.	01 Sep 2008
Anxiety Disorders	Phase 2	-	Krenitsky Pharmaceuticals, Inc.	-
Anxiety Disorders	Phase 2	-	CeNeRx BioPharma, Inc.	-
Depressive Disorder	Phase 2	-	Krenitsky Pharmaceuticals, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00739908 (CX157-200, CTgov)	Phase 2	Depressive Disorder, Major	285	CX157 (Oral CX157 60 mg TID (Total Daily Dose of 180 mg))	gpsgpfpseh(rzmqdmfpon) = hhgxspyycs bxbvttstrb (odpoqyrcue, prqptmgynl - tgvqppzpdy) View more	-	27 Jun 2012
				Placebo (Oral Placebo TID)	gpsgpfpseh(rzmqdmfpon) = onftoossac bxbvttstrb (odpoqyrcue, iwnmtkefng - mqjhiturwu) View more