A Randomized, Double-Blind, Placebo-Controlled; Phase 1b, Safety, Tolerability, and Pharmacokinetic Study of Multiple Ascending Doses of GC021109 in Subjects With Mild to Moderate Alzheimer's Disease

This is a Phase 1b, multi-center, randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, and pharmacokinetics of GC021109 in subjects with mild to moderate Alzheimer's Disease (as determined by 2011 National Institute on Aging- Alzheimer's Association [NIA-AA] criteria and Mini Mental State Examination [MMSE]). The Investigator, study site staff, (with exception of a designated pharmacist/pharmacy technician) and all study subjects will be blinded to randomized study medication assignment until database lock. Treatment assignments may be unblinded for select pre-authorized individuals involved in the safety and PK data reviews in order to accurately determine how to proceed with dose escalation.

开始日期2015-02-01

申办/合作机构

Gliacure, Inc.

NCT02254369 / Completed临床1期

A Randomized, Phase 1, Double-Blind, Placebo-Controlled, First-in-Human, Safety, Tolerability, and Pharmacokinetic Study of Single Ascending Doses of GC021109 in Healthy Subjects

The primary objective of the study is to assess the safety and tolerability of single oral doses of GC021109 when administered to healthy adult subjects.

开始日期2014-09-01

申办/合作机构

Gliacure, Inc.

100 项与 GC-021109 相关的临床结果

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100 项与 GC-021109 相关的转化医学

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100 项与 GC-021109 相关的专利（医药）

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项与 GC-021109 相关的文献（医药）

Journal of Asthma and Allergy3区 · 医学

A purinergic P2Y6 receptor agonist prodrug modulates airway inflammation, remodeling, and hyperreactivity in a mouse model of asthma

3区 · 医学

ArticleOA

作者: Chetty, Anne ; Warburton, Rod ; Castellot, John J ; Xue, Chang ; Sahagian, G Gary ; Fang, Min ; Haydon, Philip G ; Nielsen, Heber C ; Weinberg, Ellen O ; Sharda, Azeem ; Chen, Tiangmeng ; Dong, Jinghui

BACKGROUNDPurinergic receptors control cell proliferation, apoptosis, migration, inflammation, and cytokine secretion. Increased expression of specific purinergic receptors is reported in asthma. The role of purinergic P2Y6 receptors (P2Y6R) in asthma is controversial.HYPOTHESISP2Y6R activation in asthma improves pulmonary function and reduces inflammation and smooth muscle amount.METHODSFemale mice (C57/BL6, age 30 days) were randomly assigned to receive intranasal house dust mite (HDM) antigen (40 or 80 µg) or saline, 5 days/week, for 6 weeks. Randomly selected subgroups received intraperitoneal P2Y6R agonist prodrug (GC021109; 10 or 100 µg/kg weight/dose) simultaneously with HDM. After 6 weeks, lung function was measured. Lung lavage fluid (LLF) was used to measure total cell count, total protein, and cytokines. Immunohistochemistry for alpha smooth muscle actin (α-SMA) was done. Airway wall thickness was measured on micro-computed tomography (micro-CT) images.RESULTSPulmonary function testing revealed a HDM dose-dependent airway hyperresponsiveness. Airway resistance was increased 2-fold while compliance was decreased by 50% at the higher HDM dose (P<0.05). GC021109 prevented these changes. HDM-exposed mice had elevated inflammatory cell and total protein levels in LLF which were prevented by GC021109 (P<0.05). HDM mice also had elevated LLF levels of interleukin (IL)-4, IL-5, IL-12, granulocyte colony stimulating factor, chemokine (C-X-C) motif ligand 1, and leukemia inhibitory factor that were reduced by GC021109 with a dose-dependent pattern. HDM mice had increased peribronchial and perivascular inflammatory cell infiltration and increased α-SMA; these changes were absent with GC021109. Airway wall thickness measured on micro-CT images was increased after HDM exposure and significantly reduced by GC021109 treatment.CONCLUSIONThe P2Y6R prodrug GC021109 inhibited allergen-induced changes in pulmonary function, inflammatory responses, and airway and vascular smooth muscle mass. P2Y6R activation may be an effective therapeutic maintenance strategy in asthma.

100 项与 GC-021109 相关的药物交易

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