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.
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.