GS-9411(GS-9411) - 药物靶点：ENaC_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

ENaC

作用机制

ENaC阻滞剂(上皮细胞钠离子通道阻滞剂)

治疗领域

遗传病与畸形消化系统疾病呼吸系统疾病+ [1]

在研适应症-

非在研适应症

支气管扩张囊性纤维化慢性阻塞性肺疾病

原研机构

Parion Sciences, Inc.

在研机构-

非在研机构

Parion Sciences, Inc.

Gilead Sciences, Inc.

最高研发阶段终止临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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关联

4

项与 GS-9411 相关的临床试验

NCT01025713 / Withdrawn临床1期

A Phase 1, Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Safety, Tolerability, and Pharmacokinetics of GS 9411 in Subjects With Cystic Fibrosis (CF)

The purpose of this study is to evaluate the safety and tolerability of GS-9411 in patients with Cystic Fibrosis. GS-9411 is a sodium channel inhibitor, that may restore airway hydration and mucociliary clearance in the lung.

开始日期2009-12-01

申办/合作机构

Gilead Sciences, Inc.

NCT00999531 / Completed临床1期

A Phase 1, Randomized, Double-Blind, Placebo-Controlled Multiple Dose Trial to Assess the Safety, Tolerability, and Pharmacokinetics of GS-9411 in Healthy Volunteers

The purpose of this study is to evaluate the safety and tolerability of repeated doses of GS-9411 in healthy volunteers. GS-9411 is a sodium channel inhibitor, that may restore airway hydration and mucociliary clearance in the lung.

开始日期2009-10-01

申办/合作机构

Gilead Sciences, Inc.

NCT00951522 / Completed临床1期

A Phase 1 Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Safety, Tolerability, and Pharmacokinetics of GS-9411 in Healthy Male Volunteers

The purpose of this study is to evaluate the safety and tolerability of escalating doses of GS-9411 in healthy male volunteers. GS-9411 is a sodium channel inhibitor, that may restore airway hydration and mucociliary clearance in the lung.

开始日期2009-09-01

申办/合作机构

Gilead Sciences, Inc.

100 项与 GS-9411 相关的临床结果

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100 项与 GS-9411 相关的转化医学

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100 项与 GS-9411 相关的专利（医药）

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3

项与 GS-9411 相关的文献（医药）

2014-06-01·Journal of Aerosol Medicine and Pulmonary Drug Delivery4区 · 医学

Acute Hyperkalemia Associated with Inhalation of a Potent ENaC Antagonist: Phase 1 Trial of GS-9411

4区 · 医学

Article

作者: Flitter, William D. ; White, Vicki Shigekane ; Newcomb, Terry ; Boucher, Richard C. ; Donn, Karl H. ; Ansede, John H. ; Johnson, M. Ross ; Montgomery, A. Bruce ; O'Riordan, Thomas G. ; Hodsman, Peter ; Warnock, David G. ; Lewis, Sandra A.

BACKGROUNDInhaled epithelial sodium channel (ENaC) blockers are designed to increase airway surface liquid volume, thereby benefiting cystic fibrosis patients. This study evaluated the safety, tolerability, and pharmacokinetics of multiple doses of ENaC blocker GS-9411, in healthy participants.METHODSThis randomized, double-blind, placebo-controlled, parallel-group, residential, Phase 1 study evaluated inhaled GS-9411 (2.4, 4.8, and 9.6 mg) or placebo, dosed twice daily for 14 days.RESULTS AND CONCLUSIONSGS-9411 was well tolerated; 86.1% of treated participants completed dosing (n=31/36). Cough and dizziness (27.8% participants each; most of mild severity) were the most commonly reported adverse events and occurred in both placebo and GS-9411 treatment groups. Arrhythmias were not observed for GS-9411-treated participants, and electrocardiographic changes were not considered clinically significant. Serum potassium levels exceeded the upper limit of normal (>5 mmol/L), 4 hr after the morning dose in GS-9411 (n=16/24) and placebo (n=4/12) treatment groups (38 incidences total). Retesting revealed levels had returned to normal within 2-3 hr. In urine electrolyte analyses, obtained 0-6 hr after the Day 1 morning dose, mean sodium/potassium ratios significantly increased from values 0-6 hr before dosing. Increased urine sodium/potassium ratios corresponded with high urine concentrations of active GS-9411 metabolites, which inhibited sodium reabsorption in the kidney, leading to the observed transient hyperkalemia in these participants. Inhaled GS-9411 was well tolerated except for the emergence of transient clinically significant hyperkalemia; this finding resulted in termination of further clinical development of this drug and will necessitate development of a new generation of ENaC blockers, which provide a sustained improvement in mucociliary clearance, while reducing renal exposure to ENaC blockade. Transient increases in mean urine sodium/potassium ratios appeared to be the first signal of electrolyte imbalances resulting from drug-induced block of ENaC in the kidney. The results of this study strongly suggest that clinical trials of novel ENaC blockers will require intensive measurement of plasma and urine electrolyte levels.

2009-10-01·Drugs1区 · 医学

Emerging Treatments in Cystic Fibrosis

1区 · 医学

Article

作者: Andrew M. Jones ; Jennifer M. Helm

There are a number of potential drugs for the treatment of cystic fibrosis (CF) currently undergoing clinical studies. A number of antibacterials formulated for delivery by inhalation are at various stages of study; these include dry-powder inhaler versions of colistin, tobramycin and ciprofloxacin, and formulations of azteonam, amikacin, levofloxacin, ciprofloxacin and fosfomycin/tobramycin for nebulization. Clinical trials of anti-inflammatory agents, including glutathione, phosphodiesterase-5 inhibitors such as sildenafil, oral acetylcysteine, simvastatin, methotrexate, docosahexaenoic acid, hydroxychloroquine, pioglitazone and alpha1-antitrypsin, are ongoing. Ion channel modulating agents, such as lancovutide (Moli1901, duramycin) and denufosol, which activate alternate (non-CF transmembrane regulator [CFTR]) chloride channels, and GS 9411, a sodium channel antagonist, are now at the stages of clinical study and if successful, will offer a new category of therapeutic agent for the treatment of CF. Correction of the underlying gene effect, either by agents that help to correct the dysfunctional CFTR, such as ataluren, VX-770 and VX-809, or by gene transfer (gene therapy), is a particularly exciting prospect as a new therapy for CF and clinical studies are ongoing. This article reviews the exciting potential drug treatments for CF currently being evaluated in clinical studies, and also highlights some of the challenges faced by research and clinical teams in assessing the efficacy of potential new therapies for CF.

1980-05-01·Biochimica et Biophysica Acta (BBA) - Bioenergetics

The fractionation of plant photoactive pigment-protein complexes I and II

Article

作者: A.Y. Borisov ; M.D. Il'ina

The pigment-protein complexes enriched with Photosystem I (PPC-I) and Photosystem II (PPC-II) were obtained using sievorptive chromatography on DEAE-Sephadex column. Both types of complexes contain Chlorophyll a, beta-carotene and minor quantities of Chl b. Red absorbance maxima are located at 676 nm and 673 nm for PPC-I and PPC-II, respectively. The degrees of reaction centre enrichment were measured by the method of differential spectrophotometry: PPC-I has one P-700 per 35 bulk Chl a molecules, PPC-II contains one P-680 per 18 bulk Chl a molecules. The yield of PPC-II is 7--10 times lower than that of PPC-I. After one chromatographic procedure the amount of P-680 in PPC-I preparation does not exceed 7% of that of P-700, the amount of P-700 in PPC-II preparation 2% of that of P-680. The product of PPC-II degradation was studied.

100 项与 GS-9411 相关的药物交易

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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
囊性纤维化	临床1期	澳大利亚	Gilead Sciences, Inc.	2008-11-01
支气管扩张	临床1期	-	Parion Sciences, Inc.	-
支气管扩张	临床1期	澳大利亚	Gilead Sciences, Inc.	-
慢性阻塞性肺疾病	临床1期	澳大利亚	Gilead Sciences, Inc.	-
慢性阻塞性肺疾病	临床1期	-	Parion Sciences, 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


NCT00999531 (Pubmed \| J Aerosol Med Pulm Drug Deliv)	临床1期	高钾血症	36	GS-9411 (2.4 mg)	(鏇憲齋憲鏇鹹簾獵範顧) = Arrhythmias were not observed for GS-9411-treated participants 網鬱醖鏇顧鬱襯顧獵網 (艱簾膚觸齋選餘鏇觸憲 ) 更多	-	2014-06-01
				GS-9411 (4.8 mg)