Civamide Nasal Spray for the Treatment of Dry Eye

7.项目摘要/摘要 该项目是西维胺鼻喷雾剂治疗干眼症的二期临床研究。 刺激性和潜在的严重致残的眼病。如果这项研究在治疗干眼症方面取得成功 对于疾病，将继续进行进一步的临床开发，即支持提交新药的第三阶段研究 申请。目前，所有被批准用于治疗干眼症的药物都是直接滴入眼睛 可能会产生眼部副作用。西维胺鼻腔喷雾剂的独特之处在于它具有治疗作用。 局部鼻黏膜内，未检测到全身吸收，如药代动力学研究所示。 为这些患者提供一种安全有效的干眼病药物，即西瓦胺鼻腔用药 因此，喷雾将填补未得到满足的医疗需求。 西瓦胺是一种TRPV-1受体调节剂，2，3是一种具有作用机制的药物，通过 调节神经递质的合成、释放和运输。干眼病是一种眼科疾病 眼表面、泪膜和相关的眼组织，包括部分支配的粘膜腺。 4、5、6三叉神经在鼻粘膜内也有浅神经末梢。 是西维胺鼻腔喷雾剂的靶标。通过影响这些神经末梢，神经递质生理学 影响到整个神经。由于这种新的作用机制，泪水增加了 当西维胺鼻腔喷雾剂应用于鼻黏膜时，在正常人和 有三叉神经介导的头痛障碍的受试者，例如偏头痛和丛集性头痛 头痛。 这项拟议的研究是一项为期12周的双盲、车辆对照研究，研究对象为患有中度疾病的成人受试者。 严重干眼症至少6个月，至少一只眼睛每5分钟进行一次≤8席尔默试验 在筛查和基线方面。这项研究由非治疗筛查期组成，在此期间，受试者 将被要求符合研究纳入标准，随后是12周的双盲治疗期。 受试者将按1：1随机化，每组约20名受试者。主要结果变量将是 Schirmer‘s试验从基线到治疗第84天的变化。不良事件将是 在研究过程中记录下来。

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.