A Randomized, Controlled, Double-masked, Investigator-initiated Trial to Evaluate Tear Film Quality and Stability in Subjects With Dry Eye Disease Using OC-01 (Varenicline Solution) Nasal Spray 0.03 mg as Compared to Vehicle Control Nasal Spray

Study Overview
=================
Brief Summary
-----------------
A randomized, controlled, double-masked, investigator-initiated trial to evaluate tear film quality and stability in subjects with dry eye disease using OC-01 (varenicline solution) nasal spray 0.03 mg as compared to vehicle control nasal spray.

Detailed Description
-----------------
A randomized, controlled, double-masked, investigator-initiated trial to evaluate tear film quality and stability in subjects with dry eye disease using OC-01 (varenicline solution) nasal spray 0.03 mg as compared to vehicle control nasal spray.

Official Title
-----------------
A Randomized, Controlled, Double-masked, Investigator-initiated Trial to Evaluate Tear Film Quality and Stability in Subjects With Dry Eye Disease Using OC-01 (Varenicline Solution) Nasal Spray 0.03 mg as Compared to Vehicle Control Nasal Spray

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

Intervention / Treatment
-----------------
* Drug: Varenicline solution
* Drug: Placebo nasal spray (OC-01 Vehicle Nasal Spray)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects must: Provide signed written consent prior to study-related procedures Be at least 22 years of age at the screening visit Be literate and able to complete questionnaires independently Be able and willing to use the study drug and participate in all study assessments and visits Have sufficient hand strength, in the opinion of the Investigator, to be able to independently administer the study drug Have provided verbal and written informed consent Have an OSDI score ≥ 13, Demonstrate corneal fluorescein staining (CFS) score of 2 or more in at least 1 corneal region, or a sum of 4 or more for all corneal regions, based on the National Eye Institute/Industry Workshop Scale Demonstrate abnormal Cassini surface qualifier image at screening visit (at the determination of the investigator) Exclusion Criteria: Subjects must not: Have undergone ocular surgery (e.g., cataract, corneal or refractive surgical procedure) within 6 months prior to the Screening/Baseline Visit Have evidence of clinically significant ocular trauma Have active ocular Herpes simplex or Herpes Zoster infection Have ocular inflammation (uveitis, iritis, scleritis, episcleritis, conjunctivitis or keratitis, with the exception of keratoconjunctivitis sicca) at the discretion of the investigator Have ocular infection (e.g., viral, bacterial, mycobacterial, protozoan or fungal infection of the cornea, conjunctiva, lacrimal gland, lacrimal sac or eyelids. including hordeolum) Have severe (Grade 3 or 4) inflammation of the eyelid (e.g., blepharochalasis, staphylococcal blepharitis or seborrheic blepharitis) Have eyelid abnormalities that significantly affect the lid function (e.g., entropion, ectropion, tumor, edema, blepharospasm, lagophthalmos, severe trichiasis, severe ptosis) Have an ocular surface abnormality that may compromise the corneal integrity (e.g., prior chemical burn, recurrent corneal erosion, corneal dystrophy, or the effect of any other ophthalmic medication that might in the opinion of the investigator compromise the ocular surface integrity) Have a systemic condition or disease not stabilized or judged by the Investigator to be incompatible with participation in the study or with the lengthier assessments required by the study (e.g., current systemic infection, uncontrolled autoimmune disease, uncontrolled immunodeficiency disease, history of myocardial infarction or heart disease, etc.) Have chronic or recurrent epistaxis, coagulation disorders or other conditions that, in the opinion of the Investigator, may lead to clinically significant risk of increased bleeding Have had nasal or sinus surgery (including history of application of nasal cautery) or significant trauma to these areas Have any untreated nasal infection at Visit 1 Have a history of vascularized nasal polyp, severely deviated septum, chronic recurrent nosebleeds, or severe nasal obstruction Have current concomitant use of a nicotinic acetylcholine receptor agonist [Nicoderm®, Nicorette®, Nicotrol NS® (nicotine), Tabex®, Desmoxan® (cytisine), and Chantix® (varenicline)] within the previous 30 days of Visit 1 and during the treatment period. Have undergone mechanical treatment for meibomian gland dysfunction using thermal pulsation/expression (e.g., LipiFlow) or intense pulsed light (e.g., OptiLight) therapy within 6 months prior to the Screening/Baseline Visit Use topical prescription ophthalmic medications including cyclosporine and/or lifitegrast within 6 months prior to the Screening/Baseline Visit and during the treatment period Use topical ophthalmic corticosteroid therapy within 6 weeks prior to the Screening/Baseline visit and during the treatment period Use ophthalmic artificial tear drops within 2 hours prior to any of the study visits; any concurrent use of artificial tears should be continued at same frequency and with no change in brand during the treatment period Use prescription or OTC topical ophthalmic mast cell stabilizers or antihistamines within 3 days of the Screening/Baseline visit and during the treatment period (systemic agents permitted) Have a known hypersensitivity to any of the procedural agents or study drug components Be currently enrolled in an investigational drug or device study or have used an investigational drug or device within 30 days prior to the Screening/Baseline visit and during the treatment period.

Ages Eligible for Study
-----------------
Minimum Age: 22 Years

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

Accepts Healthy Volunteers
-----------------
No

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: OC-01 (varenicline solution) nasal spray 0.03 mg<br>Subjects will be randomized 1:1 to be treated with the agent delivered as a 0.05 mL intranasal spray in each nostril at the following formulations | Drug: Varenicline solution<br>* OC-01 nasal spray 0.03 mg<br>|
| Placebo Comparator: Placebo nasal spray (OC-01 Vehicle Nasal Spray)<br>Subjects will be randomized 1:1 to be treated with the agent delivered as a 0.05 mL intranasal spray in each nostril at the following formulations | Drug: Placebo nasal spray (OC-01 Vehicle Nasal Spray)<br>* Placebo nasal spray (OC-01 Vehicle Nasal Spray)<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Surface qualifier image change | Change from baseline in Cassini surface qualifier image analysis to post-administration of OC-01 (varenicline solution) nasal spray (@15 minutes) on Day 1 | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EDS | Mean change from baseline in symptom score (EDS) | Day 28 | 
| Change from baseline in surface qualifier image analysis | Change from baseline in surface qualifier image analysis to pre-administration of varenicline solution nasal spray | Day 28 | 
| Corneal fluorescein staining score | Mean change from baseline in corneal fluorescein staining score | Day 28 | 
| TBUT | Mean change from baseline in fluorescein tear breakup time (TBUT) | Day 28 | 
| QoL | Mean change from baseline in QOL questionnaire score | Day 21 | 
| Tear osmolarity | Mean change from baseline in tear osmolarity score | Day 28 | 
| VA | Mean change from baseline in visual acuity (logMAR) | Day 28 | 
| IOP | Mean change from baseline in intraocular pressure | Day 28 |