Civamide Nasal Spray for the Treatment of Dry Eye

7.项目概要/摘要 该项目是西丁胺鼻喷雾剂治疗干眼症的II期临床研究， 刺激性和潜在的严重致残性眼病。如果这项研究成功治疗干眼症， 疾病，将进行进一步的临床开发，即，支持新药备案的III期研究 应用程序.目前，所有批准用于治疗干眼症的药物都是直接滴入眼睛的 可能会有眼部副作用西伐他汀鼻喷雾剂的独特之处在于它发挥了治疗作用 如药代动力学研究所示，局部存在于鼻粘膜中，未检测到全身吸收。 为这些患者提供安全有效的干眼病药物，即，civamide鼻 因此，喷雾将填补未满足的医疗需求。 Civamide是一种TRPV-1受体调节剂，2，3是一种药物，其作用机制是通过以下方式影响神经： 调节神经递质的合成、释放和运输。干眼症是一种眼部疾病。 眼表面、泪膜和相关的眼组织，包括部分受神经支配的粘膜腺 三叉神经在鼻粘膜中也有浅表神经末梢， 是西丁胺鼻喷剂的目标通过影响这些神经末梢，神经递质生理学 影响了整个神经由于这种新的作用机制， 在正常受试者和 患有由三叉神经介导的头痛疾病的受试者，例如，偏头痛7和丛集性头痛 头痛8. 这项拟议的研究是一项12周、双盲、媒介物对照的研究，成年受试者患有中度 严重干眼症至少6个月，至少一只眼睛的Schirmer试验≤ 8/5分钟 在筛选和基线时。本研究由非治疗筛选期组成，在此期间，受试者 将需要符合研究入选标准，随后为12周双盲治疗期。 受试者将以1：1的比例随机分组，每组约20例受试者。主要结局变量为 Schirmer检验从基线至治疗期第84天的变化。不良事件将 在研究过程中记录。

7. Project Summary/Abstract The project is a Phase II clinical study of Civamide Nasal Spray for the treatment of Dry Eye Disease, an irritating and potentially severely disabling ocular disease. If this study is successful in the treatment of Dry Eye Disease, further clinical development will proceed, i.e., Phase 3 studies to support the filing of a New Drug Application. Currently, all approved medications for treating Dry Eye Disease are directly instilled into the eye with the possibility of ocular side effects. Civamide Nasal Spray is unique in that it exerts its therapeutic effect locally in the nasal mucosa without systemic absorption being detected, as shown in a pharmacokinetic study.1 The availability of a safe and effective medication for Dry Eye Disease for these patients, i.e., Civamide Nasal Spray, will thus fill an unmet medical need. Civamide, a TRPV-1 receptor modulator,2,3 is a medication with a mechanism of action that affects nerves by modulating the synthesis, release, and transport of neurotransmitters. Dry Eye Disease is a disease of the surface of the eye, tear film, and related ocular tissues, including mucosal glands, which in part, are innervated by the trigeminal nerve.4,5,6 The trigeminal nerve also has superficial nerve endings in the nasal mucosa, which are the targets of Civamide Nasal Spray. By affecting these nerve endings, neurotransmitter physiology is affected throughout the entire nerve. Increased lacrimation as a result of this novel mechanism of action has been observed when Civamide Nasal Spray is applied to the nasal mucosa in both normal subjects and subjects with headache disorders mediated by the trigeminal nerve, e.g., migraine headache7 and cluster headache8. This proposed study is a 12 week, double-blind, vehicle-controlled study of adult subjects that have moderate to severe Dry Eye Disease for at least 6 months, and a Schirmer’s Test of ≤ 8 per 5 minutes in at least one eye at screening and baseline. The study is composed of a non-treatment Screening Period during which subjects will be required to meet study inclusion criteria, followed by a 12-week Double-Blind Treatment Period. Subjects will be randomized 1:1, approximately 20 subjects per group. The primary outcome variable will be the change in the Schirmer’s Test from Baseline to Day 84 of the Treatment Period. Adverse events will be recorded during the study.