PHARMACOTHERAPRY FOR XEROSTOMIA IN SJOGREN'S SYNDROME

干燥综合征口干症的药物治疗

• 批准号: 7747363
• 负责人: Karl Donn
• 金额: $ 37.93万
• 依托单位: PARION SCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-22 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7747363
• 关键词: Adverse effects; Amiloride; Apical; Autoantibodies; Cells; Chloride Ion; Chlorides; Clinical; Clinical Research; Clinical Trials Design; Connective Tissue Diseases; Consultations; Coupled; Cross-Over Studies; Data; Development; Disease; Dose; Double-Blind Method; Drug Formulations; Dryness; Epithelial; Exocrine Glands; Funding; Goals; Hydration status; Infiltration; Inflammatory; Ions; Lead; Liquid substance; Lymphocyte; Mastication; Measures; Mediating; Mononuclear; Mouthwash; Oral; Oral cavity; Oral mucous membrane structure; Organ; Parasympathomimetic Agents; Patients; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Physiological; Pilocarpine; Placebo Control; Production; Program Development; Randomized; Research Design; Research Personnel; Running; Safety; Saliva; Salivary Glands; Sample Size; Science; Sjogren' s Syndrome; Sleep; Small Business Innovation Research Grant; Sodium; Sodium Channel; Sodium Chloride; Squamous Epithelium; Sum; Surface; Symptoms; Syndrome; Testing; Therapeutic; Therapeutic Agents; Time; Tongue; Transport Process; Treatment Efficacy; Visual; Water; Xerostomia; absorption; analog; base; design; efficacy testing; epithelial Na+ channel; eye dryness; follow-up; improved; lacrimal; novel; programs; public health relevance; research clinical testing; safety study; safety testing

DESCRIPTION (provided by applicant): Sjogren's syndrome (SS) is a slowly progressive inflammatory disease characterized by lymphocyte- mediated destruction of exocrine glands and internal organ involvement due to autoantibody production or pre- existing connective tissue disorder. Over time, progressive infiltration of lacrimal and salivary glands by mononuclear cells leads to diminished secretions, with resultant xerostomia (dry mouth) and xeropthalmia (dry eye) being the most prevalent symptoms. In Sjogren's patients, xerostomia leads to significant discomfort; interferes with activities such as speaking, chewing, and sleeping; and can result in numerous secondary clinical manifestations. Use of currently available treatments for xerostomia, including saliva substitutes and centrally acting parasympathomimetic secretagogues such as pilocarpine and cevimeline, provide transient relief, but patients often find these remedies costly, ineffective, inconvenient, and associated with uncomfortable side effects. Parion Sciences is developing 552-02, a novel epithelial sodium channel (ENaC) blocker, as a therapeutic for the indication of dry mouth. A 28-day, randomized, double-blind, placebo-controlled crossover, safety study (205S) was conducted to evaluate the safety and efficacy of 552-02 formulated as an oral rise. In study 205S, the oromucosal formulation of 552-02 was safe and well tolerated when administered 6 times daily for 28 days to patients with dry mouth associated with Sjogren's syndrome. Despite the small sample size in this exploratory study (n=30), patients' assessments of changes from baseline in symptoms of dry mouth using visual analog scales indicated 552-02 efficacy for mouth dryness, tongue dryness, and the ability to sleep, and for overall symptoms of dry mouth (global assessment). Based on these results, Parion is continuing to develop its xerostomia program and is planning a follow-up Phase II study that will be optimized to increase efficacy and patient convenience. Specifically, the proposed study (207S) is powered for efficacy measures and includes an increase in concentration of 552-02 and new trial design. Study 207S is a necessary step in the overall development program for 552-02 as a novel therapy for treating the symptoms of dry mouth associated with Sjvogren's syndrome. PUBLIC HEALTH RELEVANCE: Sjogren's syndrome is a disease that is, in part, characterized by severe dry mouth and dry eye. In Sjogren's patients, severe dry mouth leads to significant discomfort; interferes with activities such as speaking, chewing, and sleeping; and can result in other numerous disease conditions. Parion Sciences is developing a new drug that will be given as a mouth spray for the treatment of dry mouth associated with Sjogren's syndrome.

描述（由申请人提供）：干燥综合征（SS）是一种缓慢进展的炎症性疾病，其特征在于由于自身抗体产生或先前存在的结缔组织病症导致淋巴细胞介导的外分泌腺破坏和内脏器官受累。随着时间的推移，单核细胞逐渐浸润泪腺和唾液腺，导致分泌物减少，导致口干症（口干）和眼干症（干眼症）成为最常见的症状。对于干燥症患者，口干症会导致明显的不适。干扰说话、咀嚼和睡眠等活动；并可导致许多继发性临床表现。使用目前可用的口干治疗方法，包括唾液替代品和中枢作用的拟副交感神经促分泌剂，如毛果芸香碱和西维美林，可提供短暂的缓解，但患者经常发现这些疗法昂贵、无效、不方便，并且伴有令人不舒服的副作用。 Parion Sciences 正在开发 552-02，一种新型上皮钠通道 (ENaC) 阻滞剂，用于治疗口干症。进行了一项为期 28 天的随机、双盲、安慰剂对照交叉安全性研究 (205S)，以评估口服上升制剂 552-02 的安全性和有效性。在研究 205S 中，当干燥综合征相关口干患者连续 28 天每天服用 6 次时，552-02 的口腔粘膜制剂是安全的且耐受性良好。尽管这项探索性研究的样本量较小（n = 30），但患者使用视觉模拟量表对口干症状相对于基线的变化进行的评估表明，552-02 对口干、舌干和睡眠能力的功效，以及口干的整体症状（整体评估）。基于这些结果，Parion 正在继续开发其口干症项目，并计划进行后续 II 期研究，该研究将进行优化，以提高疗效和患者便利性。具体来说，拟议的研究 (207S) 为功效测量提供动力，包括增加 552-02 的浓度和新的试验设计。研究 207S 是 552-02 总体开发计划的必要步骤，作为治疗与 Sjvogren 综合征相关的口干症状的新疗法。 公共卫生相关性：干燥综合征是一种部分以严重口干和干眼为特征的疾病。对于干燥症患者，严重的口干会导致明显的不适；干扰说话、咀嚼和睡眠等活动；并可能导致其他多种疾病。 Parion Sciences 正在开发一种新药，该药物将作为口腔喷雾剂用于治疗与干燥综合征相关的口干。