Safety, Efficacy, Tolerability and Pharmacokinetics of AGN-223575 Ophthalmic Suspension in Patients With Dry Eye Disease

Study Overview
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Brief Summary
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This study will evaluate the safety, efficacy, tolerability, and systemic pharmacokinetics of 3 different doses of topical ophthalmic AGN-223575 suspension compared to AGN-223575 vehicle in patients with dry eye disease.

Conditions
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Dry Eye Syndromes

Intervention / Treatment
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* Drug: AGN-223575 ophthalmic solution
* Drug: AGN-223575 vehicle ophthalmic solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signs and symptoms of dry eye disease Has used RESTASIS and/or artificial tears in both eyes twice a day for at least 60 days. Exclusion Criteria: History of glaucoma, or ocular hypertension Diagnosis of ocular infection Use of contact lenses in the past 14 days or expected use during the study Use of any topical ophthalmic medications in the past 30 days Use of corticosteroids in the past 30 days.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AGN-223575 Dose A<br>1 drop of AGN-223575 Dose A ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose A ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days. | Drug: AGN-223575 ophthalmic solution<br>* AGN-223575 ophthalmic solution once or twice daily<br>Drug: AGN-223575 vehicle ophthalmic solution<br>* Vehicle to AGN22375 ophthalmic solution once or twice daily.<br>|
| Experimental: AGN-223575 Dose B<br>1 drop of AGN-223575 Dose B ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose B ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days. | Drug: AGN-223575 ophthalmic solution<br>* AGN-223575 ophthalmic solution once or twice daily<br>Drug: AGN-223575 vehicle ophthalmic solution<br>* Vehicle to AGN22375 ophthalmic solution once or twice daily.<br>|
| Experimental: AGN-223575 Dose C<br>1 drop of AGN-223575 Dose C ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose C ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days. | Drug: AGN-223575 ophthalmic solution<br>* AGN-223575 ophthalmic solution once or twice daily<br>Drug: AGN-223575 vehicle ophthalmic solution<br>* Vehicle to AGN22375 ophthalmic solution once or twice daily.<br>|
| Placebo Comparator: AGN-223575 Vehicle<br>1 drop of Vehicle to AGN-223575 ophthalmic solution administered in each eye twice daily for 14 day followed by 1 drop of vehicle to AGN-223575 ophthalmic solution in each eye once daily for 7 days. | Drug: AGN-223575 vehicle ophthalmic solution<br>* Vehicle to AGN22375 ophthalmic solution once or twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Conjunctival Redness Score in the Study Eye Using a 5-Point Scale | Nasal and temporal bulbar conjunctival hyperemia were graded separately in each eye by the investigator under slit-lamp magnification by assigning a score of 0 to 4 for each quadrant based on comparison to the Allergan Dry Eye Redness Scale with photographic reference where: 0=Normal, vessels of bulbar conjunctiva are easily observed; 1=Trace redness; 2=Mild redness; 3=Moderate redness; 4=Severe redness, and each score is associated with a reference photo. For each eye, the study quadrant was determined by the greater (more severe) of the baseline redness scores for nasal and temporal bulbar conjunctival hyperemia as assessed using the Allergan Dry Eye Redness Scale. If the temporal score was greater than the nasal score, then the temporal quadrant was the study quadrant for the eye and was used to assess primary efficacy; otherwise the nasal quadrant was the study quadrant. A negative change from baseline (less redness) indicates improvement. | Baseline, Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Ocular Surface Disease Index (OSDI) Total Score Using a 5-Point Scale | OSDI questionnaire consists of 12 questions regarding ocular symptoms, environmental triggers, and vision-related functioning in patients with dry eye disease. The participants rate each question on a 5-point scale where: 0=none of the time to 4=all of the time. The scores are totaled over the 12 questions and normalized/converted to a total score of 0=no disability to 100=complete disability. Higher OSDI scores are associated with greater severity. A negative change from Baseline indicates improvement. | Baseline, Day 14 | 
| Change From Baseline in Corneal Staining Score of the Study Eye Using a 6-Point Scale | The cornea is the transparent front part of the eye which covers the iris and pupil. Staining of the cornea following ocular administration of fluorescein dye was graded using a 6-point scale where: 0=no staining to 5=diffuse staining. The higher the grade score, the worse the dry eye severity. A negative change from Baseline indicates improvement. | Baseline, Day 14 | 
| Percentage of Participants With Complete Redness Response (Yes/No) in the Study Eye | A participant was considered a redness responder if the study quadrant redness score based on the Allergan Dry Eye Redness Scale in the study eye was 0=Normal (no redness). | Day 14 |