Safety and Efficacy Study of AL-53817 and AL-78843 Ophthalmic Solutions for Allergic Conjunctivitis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate two investigational ophthalmic solutions for reduction in ocular redness in subjects with allergic conjunctivitis.

Detailed Description
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Eligible subjects attended 8 study visits, 5 of which included a 3-hour period of ragweed exposure in an Environmental Exposure Chamber. At the sixth visit, subjects received study product and began dosing for up to 9 days. The final visit was the final day of dosing. Participation in this study lasted up to 68 days.

Official Title
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A Prospective, Randomized, Double-Masked, Vehicle and Active-Controlled, Safety and Efficacy Study of AL-53817 and AL-78843 Ophthalmic Solutions for the Treatment of Allergic Conjunctivitis in an Environmental Exposure Chamber (EEC) Model

Conditions
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Allergic Conjunctivitis

Intervention / Treatment
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* Drug: AL-53817 Ophthalmic Solution, 0.1%
* Drug: AL-78843 Ophthalmic Solution, 0.03%
* Drug: Dexamethasone Ophthalmic Suspension, 0.1%
* Drug: AL-53817 Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign Informed Consent Use of condom by sexually active males for the entire duration of the study. Best corrected visual acuity of 55 or greater in each eye as measured by ETDRS (letters read method). Able and willing to comply with study protocol and follow protocol instructions. Able to avoid any of the topical ocular or systemic excluded medications during the entire study period. At least 1 year subject-reported or physician-diagnosed history (prior to Screen Visit) of allergic conjunctivitis during the ragweed season. Positive skin prick test for short ragweed allergen within 12 months prior to Screen Visit. Significant staff-assessed ocular redness in at least one region in each eye within the 3 hour period of allergen exposure in the EEC (Screen Visits). Other protocol-defined inclusion criteria may apply. Exclusion Criteria: Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for at least 1 week following the last dose of investigational product. Presence of any ocular infection, history of ocular Herpes (simplex or zoster) or adenoviral infection in either eye. History of any ocular infection, physician or subject diagnosed, within 30 days prior to Screen Visit. Presence of glaucoma, past history of, or diagnosis of glaucoma or ocular hypertension. Presence of blepharitis, active rosacea affecting the ocular adnexa, meibomian gland dysfunction, follicular conjunctivitis, intraocular inflammation, or preauricular lymphadenopathy or any other ophthalmic abnormality that may affect the study outcomes. Corneal conditions affecting the corneal structure. Unwilling to discontinue contact lens wear during the study period. Any ocular surgery including ocular laser procedures within 1 year prior to Screen Visit. Current or recent (<6 months prior to Screen Visit) history of severe, unstable, or uncontrolled autoimmune, neurological, cardiovascular, hematological, hepatic, renal, psychological, respiratory, gastrointestinal and/or immunological disease or evidence of other diseases based upon a review of medical history and/or physical examination that, in the opinion of the Investigator, would preclude safe subject participation in the study. Receiving treatment for anxiety and/or depression at the Screen Visit; any history of suicide attempt. Participation in any investigational study within 30 days of Screen Visit or concomitantly with this study. Known contraindications or hypersensitivities to any of the study medications or their components Confirmed (by physician or optometrist) diagnosis of dry eye. History of sensitivity or adverse reaction to steroids. Known allergic reaction that is unresponsive to corticosteroids or non-steroidal anti-inflammatory drugs (NSAIDS). Physician diagnosed asthma (except inactive childhood asthma and exercise-induced asthma). Evidence of active inflammation in the eye as determined by the dilated fundus examination conducted at Screen C Visit. Any corneal swelling or haze as determined by the slitlamp examination conducted at Screen C Visit. Other protocol-defined exclusion criteria may apply.

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: AL-53817<br>AL-53817 Ophthalmic Solution, 0.1%, 1 drop in each eye twice daily for 6-8 days followed by 1 drop in each eye once on the last day of dosing (Day 7, 8, or 9) | Drug: AL-53817 Ophthalmic Solution, 0.1%<br> <br> |
| Experimental: AL-78843<br>AL-78843 Ophthalmic Solution, 0.03%, 1 drop in each eye twice daily for 6-8 days followed by 1 drop in each eye once on the last day of dosing (Day 7, 8, or 9) | Drug: AL-78843 Ophthalmic Solution, 0.03%<br> <br> |
| Active Comparator: Maxidex<br>Dexamethasone Ophthalmic Suspension, 0.1%, 1 drop in each eye twice daily for 6-8 days followed by 1 drop in each eye once on the last day of dosing (Day 7, 8, or 9) | Drug: Dexamethasone Ophthalmic Suspension, 0.1%<br> <br> * Other names: Maxidex®;|
| Placebo Comparator: Vehicle<br>AL-53817 Vehicle, 1 drop in each eye twice daily for 6-8 days followed by 1 drop in each eye once on the last day of dosing (Day 7, 8, or 9) | Drug: AL-53817 Vehicle<br>* Inactive ingredients used for masking purposes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Ocular Redness, Area Under the Curve From Time Zero to Hour 10 [AUC (0-10)] at Day 7 | Ocular redness ratings were collected for nasal and temporal areas of each eye and assessed by investigational center staff using a visual scale (ie, scored by comparing the subject's eye with a series of photographs) and graded on a scale from 0 (none) to 4 (extremely severe), 0.5 unit steps permitted. AUC was calculated using the trapezoidal rule with unequal intervals as determined by the assessment time points. Change was calculated as AUC(0-10)[Day 7] - AUC(0-10) [Baseline]. Both eyes contributed to the analysis. | 0.0, 0.25, 0.50, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, and 10.0 hours on Days 1 (baseline) and 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Ocular Itching, Area Under the Curve From Time Zero to Hour 10 [AUC (0-10)] at Day 7 | Ocular itching was assessed by the subject with both eyes rated together and scored on a scale from 0 (none) to 4 (incapacitating itch with irresistible urge to rub). AUC was calculated using the trapezoidal rule with unequal intervals as determined by the assessment time points. Change was calculated as AUC(0-10)[Day 7] - AUC(0-10) [Baseline]. | 0.0, 0.25, 0.50, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, and 10.0 hours on Days 1 (baseline) and 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ragweed, Allergies, Itchy eyes, Ocular redness, Chemosis, Tearing, Watery eyes, Allergic conjunctivitis, Red eyes, Eyelid swelling