Safety and Efficacy of Single-use Cliradex Pads for Ocular Mites

描述（由申请人提供）：蠕形螨是微小的体外寄生虫，通常感染皮肤的毛囊皮脂腺单位。螨虫不受控制的过度生长与皮肤丘疹性病变、面部酒渣鼻和眼部炎有关。眼睑炎（眼睑边缘炎症）是最常见的眼病之一，它与眼睫毛中含有螨虫的圆柱形头皮屑有关。常规的治疗方法，使用婴儿洗发水刷眼睑，对根除眼蠕形螨感染（蠕形螨病）无效。然而，我们发现茶树油（TTO）是一种从交替千层树叶中蒸汽蒸馏出来的天然精油，对眼蠕虫病有有效的治疗作用。我们的初步临床研究表明，眼睑磨砂方案，基于每周在办公室磨砂50%的TTO，然后每天在家里用茶树洗发水磨砂，有效地解决了刺激症状和眼表炎症，并改善了许多患者的视力。然而，这种治疗不方便患者自行给药，并导致一些患者眼部刺激。我们已经完成了I期申请中描述的以下三个目标，以确定TTO中负责杀死蠕形螨的最有效成分，并消除剩余成分，从而开发一次性Cliradex(R) pad，以方便患者自我给药（目标1）。完成临床前安全性研究，以验证这种新的Cliradex(R) Pad是基于体外细胞毒性试验和人体受试者9次重复损伤贴片试验的无刺激性（目标2），并证明新配方具有有效的抗微生物作用，因此无需添加防腐剂，并且在玻璃罐和包装中都是稳定的（目标3）。在这个

DESCRIPTION (provided by applicant): Demodex mites are microscopic ectoparasites that commonly infest the pilosebaceous unit of the skin. Uncontrolled overgrowth of mites has been implicated in causing papulopustular lesions in the skin, rosacea in the face, and blepharitis in the eye. Blepharitis (lid margin inflammation) associated with mite-harboring cylindrical dandruff in eyelashes is one of the most common eye diseases. The conventional treatment, using lid scrub with Baby Shampoo, is ineffective in eradicating ocular Demodex infestation (demodicosis). However, we have discovered that tea tree oil (TTO), a natural essential oil steam-distilled from the leaf of Melaleuca alternifolia, is effective in treating ocular demodicosi. Our preliminary clinical studies showed that the lid scrub regimen, based on a weekly office scrub with 50% TTO followed by daily home scrubs with tea tree shampoo, is effective in resolving irritating symptoms and ocular surface inflammation, as well as in improving vision in a number of patients. However, this treatment was not convenient for patient self-administration and resulted in ocular irritation in some patients. We have completed the following three Aims described in Phase I application to identify the most active ingredient in TTO responsible for killing Demodex mites and to eliminate the remaining ingredients in order to develop single-use Cliradex(R) Pads to facilitate the patient's ease of self- administration (Aim 1), to complete preclinical safety studies to verify that this new Cliradex(R) Pad was non- irritative based on an in vitro cytotoxic assay and 9 Repeated Insult Patch Test in human subjects (Aim 2), and to demonstrate that the new formulation exerts potent anti-microbial effects, thus eliminating the need to add preservatives, and is stable both in the glass jar and in the packette (Aim 3). In this Phase II application, we propose to conduct randomized, double-blind, controlled clinical trials to demonstrate the safety and efficacy of the single-use Cliradex(R) Pad compared to the Placebo Pad for treating ocular demodicosis. In Aim 1, at a single site, we will determine the optimal regimen for applying Cliradex(R) Pads to achieve maximal reduction in ocular Demodex counts and clinical improvement in patients' symptoms and signs without eliciting adverse events by comparing three different lid scrub regimens for a period of 1 month. In Aim 2, at multiple sites, we will use the lid scrub regimen optimized in Aim 1 to determine the optimal duration to achieve maximal reduction of ocular Demodex counts and maximal efficacy in resolving patient's inflammatory symptoms and signs. Accomplishment of these two Aims will allow us to gather data for Phase III FDA pivotal studies so that an NDA can be submitted to for the ultimate goal of developing the first FDA-approved prescription ophthalmic therapy containing the most active ingredient of TTO to eradicate ocular demodicosis.