A Double-Blind, Placebo-Controlled, Cross Over Study Using a Latin Square Design to Evaluate the Safety, Tolerability, and Efficacy of NGX267 Oral Capsules in Patients With Xerostomia Associated With Sjogren's Syndrome

The purpose of this study is to evaluate the effectiveness of NGX267 in the improvement of decreased salivary flow associated with primary or secondary Sjögren's syndrome.
For each patient, the study includes four periods of treatment separated by a washout period that may range from 4 - 8 days according to patient and site discretion. Each treatment period includes two overnight stays in the clinic. One dose of study drug is taken during each treatment period

开始日期2008-02-01

申办/合作机构

TorreyPines Therapeutics, Inc.

100 项与 NGX-267 相关的临床结果

登录后查看更多信息

100 项与 NGX-267 相关的转化医学

登录后查看更多信息

100 项与 NGX-267 相关的专利（医药）

登录后查看更多信息

项与 NGX-267 相关的文献（医药）

2016-01-01·Neurodegenerative Diseases4区 · 医学

AF710B, a Novel M1/σ1 Agonist with Therapeutic Efficacy in Animal Models of Alzheimer's Disease

4区 · 医学

Article

作者: Eitan Gershonov ; Rodrigo Medeiros ; Niva Natan ; Hanoch Elkon ; Ilya Bezprozvanny ; Frank M. LaFerla ; Victoria Nahum ; Abraham Fisher ; Rachel Brandeis ; Lili Wu ; Nira Bar-Ner ; Daniel A. Ryskamp

We previously developed orthosteric M1 muscarinic agonists (e.g. AF102B, AF267B and AF292), which act as cognitive enhancers and potential disease modifiers. We now report on a novel compound, AF710B, a highly potent and selective allosteric M1 muscarinic and σ1 receptor agonist. AF710B exhibits an allosteric agonistic profile on the M1 muscarinic receptor; very low concentrations of AF710B significantly potentiated the binding and efficacy of carbachol on M1 receptors and their downstream effects (p-ERK1/2, p-CREB). AF710B (1-30 µg/kg, p.o.) was a potent and safe cognitive enhancer in rats treated with the M1 antagonist trihexyphenidyl (passive avoidance impairment). These effects of AF710B involve σ1 receptor activation. In agreement with its antiamnesic properties, AF710B (at 30 n<smlcap>M</smlcap>), via activation of M1 and a possible involvement of σ1 receptors, rescued mushroom synapse loss in PS1-KI and APP-KI neuronal cultures, while AF267B (1 µ<smlcap>M</smlcap>) was less potent in PS1-KI and ineffective in APP-KI models, respectively. In female 3xTg-AD mice, AF710B (10 µg/kg, i.p./daily/2 months) (i) mitigated cognitive impairments in the Morris water maze; (ii) decreased BACE1, GSK3β activity, p25/CDK5, neuroinflammation, soluble and insoluble Aβ<sub>40</sub>, Aβ<sub>42</sub>, plaques and tau pathologies. AF710B differs from conventional σ1 and M1 muscarinic (orthosteric, allosteric or bitopic) agonists. These results highlight AF710B as a potential treatment for Alzheimer's disease (e.g. improving cognitive deficits, synaptic loss, amyloid and tau pathologies, and neuroinflammation) with a superior profile over a plethora of other therapeutic strategies.

2009-03-01·European Journal of Pharmacology3区 · 医学

Pharmacological comparison of muscarinic ligands: Historical versus more recent muscarinic M1-preferring receptor agonists

3区 · 医学

Article

作者: Pausch, Mark H. ; Uveges, Albert J. ; Tseng, Eugene ; Butera, John A. ; Popiolek, Mike ; Kramer, Angela ; Kowal, Dianne ; Carrick, Tikva ; Lock, Tim ; Heinrich, Julia N. ; Marquis, Karen L. ; Mayer, Scott C. ; Sun, Shaiu-Ching

In functional assay assessments using the five muscarinic receptor subtypes, a second generation of muscarinic M(1)-preferring receptor agonists [AC-42 (1), AC-260584 (2), 77-LH-28-1 (3) and LY-593039 (4)] was shown to have higher selectivity for muscarinic M(1) over M(3) receptor as compared to historical agonists [talsaclidine (8), sabcomeline (10), xanomeline (11), WAY-132983 (12), cevimeline (9) and NGX-267 (6)]. Another striking difference of these more recent compounds is their affinities for the dopamine D(2) and 5-HT(2B) receptors. Taken together, these results suggest that the newer compounds may have a greater clinical safety profile, especially with regard to muscarinic M(3) receptor-mediated events, than the historical agonists, but their affinities for other receptors may still compromise their use to validate the therapeutic potential of muscarinic M(1) receptor agonists.

2009-02-25·Journal of Biopharmaceutical Statistics4区 · 医学

An Adaptive First in Man Dose-Escalation Study of NGX267: Statistical, Clinical, and Operational Considerations

4区 · 医学

Article

作者: Murphy, Michael ; Ivanova, Anastasia

The primary objective of the dose-escalation trial for NGX267 was to estimate the maximally tolerated dose (MTD) and to gather detailed clinical and pharmacokinetic observations near the MTD. The MTD was defined based on the weighted average of moderate and severe adverse events. An adaptive design was employed to concentrate dosage assignments at or near the MTD. Favoring the acquisition of data near the MTD, at the expense of information at lower dosage levels, resulted in a shorter trial and no loss of the type of information required to inform subsequent studies where larger normal volunteer or patient samples are evaluated.

100 项与 NGX-267 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05152

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
干燥综合征	临床2期	美国	TorreyPines Therapeutics, Inc.	2008-02-01
失盐型肾上腺皮质综合症	临床2期	美国	TorreyPines Therapeutics, Inc.	2008-02-01
阿尔茨海默症	临床2期	-	Raptor Pharmaceutical, Inc.	-
认知障碍	临床2期	-	Raptor Pharmaceutical, Inc.	-