Dry Eye Disease Study With Brimonidine

Study Overview
=================
Brief Summary
-----------------
To evaluate the tolerability and preliminary efficacy of Brimonidine eye drops (with and without corticosteroid eye drops) for the treatment of Dry Eye Disease (DED).

Detailed Description
-----------------
Subjects will assess their tolerance to the administration of the study drug, utilizing a Visual Analog Scale (VAS). The VAS is a 100-mm horizontal line with verbal descriptors at either end. The VAS ratings will be completed after administration of the study drug on Day 1 (post-dose), Day 28, Day 56, Day 84, and Day 105. Subjects will place a single slash mark across the horizontal line between the end labeled completely intolerable (0 mm) and easily tolerable (100mm).

Official Title
-----------------
A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Proof-of-Concept Study of Brimonidine Eye Drops for the Treatment of Dry Eye Disease (DED)

Conditions
-----------------
Dry Eye

Intervention / Treatment
-----------------
* Drug: Brimonidine
* Drug: Brimonidine Mono Therapy
* Drug: sodium carboxymethylcellulose
* Drug: Corticosteroid Eye Drop


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 18 years or older. Sign and date informed consent form approved by the IRB History of Dry Eye Disease Objective evidence of DED in at least one eye by having 2 or more of the following 4 signs in the same eye at Screening and Baseline (Day 1) visits: i. Conjunctival staining at >/= 1 (out of a possible score of 6 per eye) ii. Corneal staining at >/= 2 (out of a possible score of 15 per eye) iii. Noninvasive Tear Break-Up Time (NITBUT) at </= 7 seconds iv. Schirmer test at <10mm in 5 minutes Symptomatic evidence of DED by having a global symptom score (SANDE) >/= 25 mm at both Screening and Baseline (Day 1) visits Intraocular pressure (IOP) >/= 5 mmHg and </= 22 mmHg in each eye Women who satisfy one of the following: Are of child-bearing potential (WOCP) who are not pregnant or lactating and who are either abstinent or sexually active on an acceptable method of birth control for at least 4 weeks prior to Visit 1 and throughout the study, OR Are post-menopausal or have undergone a sterilization procedure Exclusion Criteria: Allergic to brimonidine, corticosteroids or any similar products, or excipients of brimonidine including benzalkonium chloride (BAK) Use of contact lenses Currently receiving brimonidine or other treatment for glaucoma or ocular hypertension or history of glaucoma surgery. Receiving or have received any experimental or investigational drug or device within 30 days prior to Screening visit Intraocular pressure <5 mmHg or >22 mmHg in either eye Active ocular infection or history of ocular herpetic keratitis History of neurotrophic keratitis or ocular neuropathic pain Any history of eyelid surgery or intraocular/ocular surgery within the past 3 months Punctal occlusion within 3 months prior to Screening visit or during study Corneal epithelial defect larger than 1 mm2 in either eye Have active drug/alcohol dependence or abuse history Are neonates, pregnant/lactating women, children, institutionalized individuals, or others who may be considered vulnerable populations Received corticosteroid-containing eye drops within the past 7 days or systemic corticosteroids/immunosuppressives within the past 3 months Received cyclosporine ophthalmic emulsion 0.05% (Restasis®) or lifitegrast ophthalmic solution 5% (Xiidra™) within 30 days prior to Screening visit In the opinion of Investigator or Study Coordinator, be unwilling or unable to comply with study protocol or unable to successfully instill eye drops Disease, condition, or disorder that in the judgement of Investigator could confound study assessments or limit compliance to study protocol

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Drug Arm #1<br>Combination Therapy: brimonidine (0.2%) administered as eye drops, followed by corticosteroid eye drops, two times a day (BID) for 12 weeks | Drug: Brimonidine<br>* Two products delivered in sequence twice daily.<br>Drug: Corticosteroid Eye Drop<br>* Eye drop to be administered after Brimonidine in treatment arm 1<br>|
| Experimental: Study Drug Arm #2<br>Monotherapy: brimonidine (0.2%) administered as eye drops followed by placebo, two times a day (BID) for 12 weeks | Drug: Brimonidine Mono Therapy<br>* Brimonidine given twice daily along with placebo drops<br>|
| Placebo Comparator: Control Arm<br>Placebo: sodium carboxymethylcellulose (0.25%) administered as eye drops followed by a second application, two time a day (BID) for 12 weeks | Drug: sodium carboxymethylcellulose<br>* Placebo given twice daily.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerance of Test Substance Visual Analogue Scale (VAS) Score | Participants assessed their tolerance to the administration of the study drug, utilizing a VAS. The VAS is a 100-mm horizontal line with verbal descriptors at either end. Participants placed a single slash mark across the horizontal line between the end labeled completely intolerable (0 mm) and easily tolerable (100mm). | Days 1, 28, 56, and 84 |