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

一次性 Cliradex 眼螨垫的安全性和功效

基本信息

批准号：
8394720
负责人：
SCHEFFER CG TSENG
金额：
$ 55.22万
依托单位：
TISSUETECH, INC.
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-01 至 2015-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8394720
关键词：
Adult Adverse event Biological Assay Blepharitis Clinical Clinical Research Controlled Clinical Trials Cornea Cosmetics Data Development Diagnostic Procedure Disadvantaged Double-Blind Method Drug Formulations Exclusion Exhibits Eye Eye diseases Eyelash FDA approved Face Glass Goals Grant Home environment In Vitro Incidence Inflammation Inflammatory Investigational New Drug Application Lesion Life Cycle Stages Marketing Melaleuca alternifolia Methods Microscopic Mites Modification Monitor Mono-S Ointments Patch Tests Patients Phase Placebos Plague Plant Leaves Play Randomized Regimen Role Rosacea Safety Sampling Self Administration Signs and Symptoms Site Skin Steam Symptoms Tea Tea Tree Oil Terpenes Testing Therapeutic Agents Trees Vision Volatile Oils aging population antimicrobial base clinical efficacy clinical research site conventional therapy cytotoxic human subject improved irritation killings ocular surface preclinical safety safety study

项目摘要

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. PUBLIC HEALTH RELEVANCE: Our proposed randomized, double-blind, controlled clinical trials described in this Phase II application aim to demonstrate the clinical safety and efficacy o single-use Cliradex(R) Pads that contain the most active ingredient identified during the Phase I grant from tea tree oil to eradicate ocular demodicosis. During Phase I, we have gathered strong data supporting that the new formulation also exerts unique broad-spectrum anti- microbial effects, thus eliminating the need for adding preservatives. Furthermore, we have verified that this new formulation is not irritative based on an in vitro cytotoxic assay and 9 Repeated Insult Patch Test in human subjects, and the new formulation is stable both in the glass jar and in the packette. Hence, our accomplishments during Phase I justifies our further pursuit of the two Aims described herein so that we may eventually develop a new safe, effective, and convenient treatment for eradicating ocular demodicosis, which is one of the most common causes of blepharitis that has plagued patients with ocular irritation, especially in our aging population.

描述（由申请人提供）：蠕形螨是一种微小的体外寄生虫，通常侵染皮肤的毛囊皮脂腺单位。螨虫不受控制的过度生长可能导致皮肤丘疹脓疱性病变、面部红斑痤疮和眼睑炎。与睫毛中含有螨虫的圆柱形头皮屑相关的睑缘炎（眼睑边缘炎症）是最常见的眼部疾病之一。传统的治疗方法是使用婴儿洗发水和眼睑磨砂膏，无法有效根除眼部蠕形螨感染（蠕形螨病）。然而，我们发现茶树油（TTO）是一种从互叶白千层叶中蒸汽蒸馏的天然精油，可有效治疗眼部蠕形螨病。我们的初步临床研究表明，眼睑磨砂疗法（每周用 50% TTO 进行办公室磨砂，然后每天用茶树洗发水进行家庭磨砂）可有效解决刺激症状和眼表炎症，并可改善视力。患者数量。然而，这种治疗不方便患者自行给药，并且导致一些患者出现眼部刺激。我们已经完成了第一阶段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，以开发一次性 Cliradex(R) 垫，以方便患者自行使用- 给药（目标 1），完成临床前安全性研究，以根据体外细胞毒性测定和 9 次重复侮辱验证这种新型 Cliradex(R) 垫无刺激性在人类受试者中进行斑贴测试（目标 2），并证明新配方具有有效的抗菌作用，从而无需添加防腐剂，并且在玻璃罐和小包中均稳定（目标 3）。在这个 II期申请，我们建议进行随机、双盲、对照临床试验与安慰剂垫相比，证明一次性 Cliradex(R) 垫在治疗眼部蠕形螨病方面的安全性和有效性。在目标 1 中，我们将通过比较三种不同的眼睑擦洗方案，在单一部位确定应用 Cliradex(R) 垫的最佳方案，以最大程度地减少眼部蠕形螨计数并改善患者症状和体征，同时不会引发不良事件为期1个月。在目标 2 中，我们将在多个部位使用目标 1 中优化的眼睑擦洗方案，以确定最佳持续时间，以最大程度地减少眼部蠕形螨数量并最大程度地缓解患者的炎症症状和体征。这两个目标的实现将使我们能够收集 FDA III 期关键研究的数据，以便可以提交新药申请 (NDA)，以实现开发第一个 FDA 批准的含有 TTO 最活性成分的眼科处方疗法的最终目标，以根除眼部蠕形螨病。公共健康相关性：我们在本 II 期申请中描述的拟议随机、双盲、对照临床试验旨在证明一次性 Cliradex(R) 垫的临床安全性和有效性，该垫含有 I 期拨款期间确定的最有效成分茶树油可根除眼部蠕形螨病。在第一阶段，我们收集了强有力的数据，支持新配方还发挥独特的广谱抗菌作用，从而无需添加防腐剂。此外，根据体外细胞毒性试验和人体9次重复侮辱斑贴试验，我们已经证实这种新配方不具有刺激性，并且新配方在玻璃罐和小包装中都很稳定。因此，我们在第一阶段取得的成就证明了我们进一步追求本文所述的两个目标，以便我们最终可以开发出一种新的安全、有效和方便的治疗方法来根除眼蠕形螨病，眼蠕形螨病是困扰眼睑炎的最常见原因之一。患有眼部刺激的患者，特别是在我们的老龄化人口中。