Safety and Efficacy of KPI-121 Compared to Placebo in Subjects With Dry Eye Disease

Study Overview
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Brief Summary
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The primary purpose of this study is to determine the efficacy and safety of KPI-121 0.25% ophthalmic suspension compared to vehicle (placebo) in subjects who have a documented clinical diagnosis of dry eye disease. The product will be studied over 14 days, with 1-2 drops instilled in each eye four times daily (QID).

Detailed Description
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This is a Phase 3, multi-center, double-masked, randomized, vehicle-controlled, parallel-group study designed to evaluate the safety and efficacy of KPI-121 0.25% ophthalmic suspension versus vehicle in subjects with dry eye disease.

Official Title
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A Phase 3, Double-Masked, Randomized, Controlled Study of KPI-121 0.25% Ophthalmic Suspension Compared to Vehicle in Subjects With Dry Eye Disease

Conditions
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Dry Eye Syndromes, Keratoconjunctivitis Sicca

Intervention / Treatment
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* Drug: KPI-121 0.25% Ophthalmic Suspension
* Drug: Vehicle of KPI-121 0.25% Ophthalmic Suspension


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a documented clinical diagnosis of dry eye disease in both eyes Exclusion Criteria: Known hypersensitivity or contraindication to the investigational product(s) or components History of glaucoma, IOP>21 mmHg at the screening or randomization visits, or being treated for glaucoma in either eye. Diagnosis of: ongoing ocular infection; severe/serious ocular condition that in judgment of Investigator could confound study assessments or limit compliance; or have been exposed to an investigational drug within 30 days prior to screening. In the opinion of the Investigator or study coordinator, be unwilling or unable to comply with study protocol or unable to successfully instill eye drops.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: KPI-121 0.25% Ophthalmic Suspension<br> | Drug: KPI-121 0.25% Ophthalmic Suspension<br> <br> * Other names: Loteprednol etabonate;|
| Placebo Comparator: Vehicle of KPI-121 0.25% Ophthalmic Suspension<br> | Drug: Vehicle of KPI-121 0.25% Ophthalmic Suspension<br> <br> * Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline/Visit 2 (Day 1) in Bulbar Conjunctival Hyperemia at Visit 4 (Day 15) | Comparison of mean change from baseline for bulbar conjunctival hyperemia in the study eye between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-4 grading scale. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe. | Baseline/Visit 2 (Day 1) - Visit 4 (Day 15) | 
| Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity at Visit 4 (Day 15) | Comparison of mean ocular discomfort between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse. | Baseline/Visit 2 (Day 1) - Visit 4 (Day 15) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects With ≥ 1 Unit Improvement From Baseline/Visit 2 (Day 1) in Bulbar Conjunctival Hyperemia Worst Region at Visit 4 (Day 15) | Proportion of subjects with ≥1 improvement from baseline in conjunctival hyperemia scores in the study eye. The grading scale was based on the Cornea and Contact Lens Research Unit Grading Scale where 0 = none, 1 = very slight, 2 = slight, 3 = moderate and 4 = severe. | Baseline/Visit 2 (Day 1) - Visit 4 (Day 15) | 
| Change From Baseline/ Visit 2 (Day 1) in Ocular Discomfort Severity Scores at Visit 3 (Day 8) | Comparison of ocular discomfort scores between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse using 3-day mean scores. | Baseline/Visit 2 (Day 1) - Visit 3 (Day 8) | 
| Change From Baseline/Week 2 (Day 1) in Ocular Discomfort Scores to Day 4 | Comparison of mean ocular discomfort between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse. | Baseline/Visit 2 (Day 1) - Day 4 | 
| Change From Baseline/Week 2 (Day 1) in Ocular Discomfort Severity at Visit 4 (Day 15) in a Subgroup | Comparison of mean ocular discomfort between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse, in a sub-group of participants with more severe ocular discomfort at baseline, using 3 day means. | Baseline/Visit 2 (Day 1) - Visit 4 (Day 15) | 
| Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Severity Scores at Day 3 (Diary) | Comparison of mean ocular discomfort severity between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse. | Baseline/Visit 2 (Day 1) - Day 3 | 
| Change From Baseline/Visit 2 (Day 1) in Eye Dryness Scores at Visit 4 (Day 15) | Comparison of mean eye dryness between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse. | Baseline/Visit 2 (Day 1) - Visit 4 (Day 15) | 
| Change From Baseline/Visit 2 (Day 1) in Eye Dryness Scores at Visit 3 (Day 8) | Comparison of mean eye dryness between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse. | Baseline/Visit 2 (Day 1) - Visit 3 (Day 8) | 
| Ocular Discomfort Severity Scores on Day 2 (Diary) Minus Baseline/Visit 2 (Day 1) | Comparison of mean ocular discomfort between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse. | Baseline/Visit 2 (Day 1) - Day 1 | 
| Change From Baseline/Visit 2 (Day 1) in Ocular Discomfort Frequency Scores at Visit 4 (Day 15) | Comparison of mean ocular discomfort frequency between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse. | Baseline/Visit 2 (Day 1) - Visit 4 (Day 15) | 
| Change From Baseline/Visit 2 (Day 1) in Subject-rated Ocular Discomfort Frequency Scores at Visit 3 (Day 8) | Comparison of mean ocular discomfort frequency between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using a 0-100 visual analog grading scale where 0 was better and 100 was worse. | Baseline/Visit 2 (Day 1) - Visit 3 (Day 8) | 
| Change From Baseline/Visit 2 (Day 1) in Inferior Corneal Fluorescein Staining Score at Visit 4 (Day 15) | Comparison of mean corneal fluorescein staining in the study eye between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using methods developed by the National Eye Institute (NEI) Dry Eye Workshop in evaluating 5 regions of the cornea (superior, inferior, nasal, temporal and central) using a 0-3 grading scale, where 0 = no visible staining, 1 = Mild, 2 = moderate and 3 = severe. | Baseline/Visit 2 (Day 1) - Visit 4 (Day 15) | 
| Change From Baseline/Visit 2 (Day 1) in Nasal Corneal Fluorescein Staining Score at Visit 4 (Day 15) | Comparison of mean nasal corneal fluorescein staining in the study eye between the KPI-121 0.25% ophthalmic suspension group and the vehicle group using methods developed by the National Eye Institute (NEI) Dry Eye Workshop in evaluating 5 regions of the cornea (superior, inferior, nasal, temporal and central) using a 0-3 grading scale, where 0 = no visible staining, 1 = Mild, 2 = moderate and 3 = severe. | Baseline/Visit 2 (Day 1) - Visit 4 (Day 15) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ocular Discomfort, Pain, Corticosteroid, Hyperemia, Dry Eye