Evaluation of P-321 Ophthalmic Solution Compared to Placebo in Subjects With Dry Eye Disease

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of treatment with 0.017% P-321 on Dry Eye Symptoms.

Detailed Description
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This is a multi-center, randomized, double-masked, placebo-controlled, parallel group Phase 2b trial designed to evaluate symptoms and signs in subjects with mild to moderate dry eye disease. Eligible patients, will be treated with placebo during 2-week placebo run-in period. Subjects will then be randomly assigned in a double-masked, 1:1 ratio to either 0.017% P-321 Ophthalmic Solution or placebo TID for 28 days. This study is designed to evaluate the changes in symptoms. Safety will be assessed throughout the study by adverse events.

Official Title
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Randomized, Double-Masked, Parallel Group Study of P-321 Ophthalmic Solution Compared to Placebo in Subjects With Dry Eye Disease Assessing Safety and Efficacy Over 28 Days

Conditions
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Dry Eye Disease

Intervention / Treatment
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* Drug: P-321 Ophthalmic Solution
* Drug: P-321 Ophthalmic Solution placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent Male or female subjects aged 18 to 80 years, inclusive Have a history of dry eye disease (DED) in both eyes Be on stable regimens of other needed medications Have a BCVA of +0.7 or better as assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS) Have reported symptoms Have the following signs in at least one eye: Schirmer score without anesthesia of >1 and <10 mm at 5 minutes and staining of conjunctival and corneal areas of the eye. Have normal lid anatomy Exclusion Criteria: Have undergone refractive eye surgery in the past 12 months Have undergone previous eyelid surgery in either eye (External blepharoplasty not resulting in exposure or abnormal blinking is allowed) Have lid irregularities or deformities Have a history of glaucoma, a history of an elevated lOP within the past year, or an lOP in either eye > 25 mmHg at the Screening Visit (Visit 1) Have any clinically significant, uncontrolled, or unstable medical or surgical conditions that could affect his or her ability to participate Have permanent punctal plugs, punctal occlusion, or history of nasolacrimal duct obstruction. Removable punctal plugs are allowed if they have been used regularly for at least 60 days prior to the screening visit. However, if a plug comes out during the study it must be promptly replaced. Have clinical findings of severe Meibomian Gland Dysfunction (MGD) in the Study Eye Are pregnant or breast feeding Use of any investigational product or device within 28 days prior to the Screening Visit or during the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: 0.017% P-321 Ophthalmic Solution<br>0.017% P-321 Ophthalmic Solution TID for 28 days. | Drug: P-321 Ophthalmic Solution<br>* P-321 Ophthalmic Solution 0.017%<br>* Other names: P-321;|
| Placebo Comparator: Placebo<br>P-321 Ophthalmic Solution Placebo TID for 28 days. | Drug: P-321 Ophthalmic Solution placebo<br>* Placebo to match P-321 Ophthalmic Solution<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) to Day 29 (Visit 4) in the Subject-reported Dry Eye Symptom Questionnaire. | Dry Eye symptoms were obtained using the Symptom Assessment in Dry Eye (SANDE) questionnaire. The questionnaire utilizes separate Visual Analog Scales (VAS) for the frequency and the Severity of symptoms. The scores range from 0 to 100 where 0 = Rarely or Very Mild, and 100 = All the Time or Very Severe for the Frequency and Severity of the symptoms, respectively. The Global Score as reported in the Primary Outcome is obtained by taking the square root of the product of the frequency score multiplied by the severity score. Negative change from baseline indicates improvement. | Baseline to Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline (Visit 2) to Day 29 in Symptom Frequency Scores | Dry Eye symptom frequency was obtained using the Symptom Assessment in Dry Eye (SANDE) questionnaire. The questionnaire utilizes a 100 mm horizontal Visual Analog Scale (VAS). The scores range from 0 to 100 where 0 = Rarely and 100 = All the Time. A negative change from baseline indicates improvement. | Baseline to Day 29 | 
| Change From Baseline (Visit 2) to Day 29 in Symptom Severity Scores | Dry Eye symptom severity was obtained using the Symptom Assessment in Dry Eye (SANDE) questionnaire. The questionnaire utilizes a 100 mm horizontal Visual Analog Scales (VAS). The scores range from 0 to 100 where 0 = Very Mild and 100 = Very Severe. A negative change from baseline indicates improvement. | Baseline to Day 29 | 
| Change From Baseline to Day 29 in Fluorescein Staining of the Cornea. | Corneal staining was performed to grade the corneal epithelial cell injury as measured by fluorescence using slit lamp examination. The staining was graded with the NEI scale. The corneal surface is divided into 5 corneal regions (1, Central; 2, Inferior; 3, Nasal; 4, Temporal; 5, Superior). The scores for each of these 5 regions ranged from 0 to 3 (0=no staining; 1=staining with low density; 2=staining with moderate density; 3=staining with severe density). The total staining score (sum of all regions, maximal score =15) is reported. A negative change from baseline indicates improvement. | Baseline to Day 29 | 
| Change From Baseline to Day 29 in Lissamine Green Staining of the Conjunctiva. | Conjunctival staining was performed to grade the conjunctival epithelial cell injury as measured by Lissamine Green using slit-lamp examination. The staining was graded with the NEI scale. The bulbar conjunctival surface is divided into 6 regions (1, Temporal; 2 Temporal Superior; 3, Temporal Inferior; 4, Nasal Superior; 5, Nasal Inferior; 6, Nasal). The scores for each of these 6 regions ranged from 0 to 3 (0=no staining; 1=staining with low density; 2=staining with moderate density; 3=staining with severe density). The total staining score (sum of all regions, maximal score =18) is reported. A negative change from baseline indicates improvement. | Baseline to Day 29 | 
| Number of Participants With at Least 20% Improvement in Symptoms From Baseline to Day 29 | Improvement in symptoms was evaluated using the Symptom Assessment in Dry Eye (SANDE) questionnaire. The questionnaire utilizes separate Visual Analog Scales (VAS) for the frequency and the Severity of symptoms. The scores range from 0 to 100 where 0 = Rarely or Very Mild, and 100 = All the Time or Very Severe for the Frequency and Severity of the symptoms, respectively. The Global Score is obtained by taking the square root of the product of the frequency score multiplied by the severity score. Lower scores indicate improvement in symptoms. | Baseline to Day 29 | 
| Change From Baseline (Visit 2) to Day 15 (Visit 3) in the Subject-reported Dry Eye Symptom Score. | Dry Eye symptoms were obtained using the Symptom Assessment in Dry Eye (SANDE) questionnaire. The questionnaire utilizes separate Visual Analog Scales (VAS) for the frequency and the Severity of symptoms. The scores range from 0 to 100 where 0 = Rarely or Very Mild, and 100 = All the Time or Very Severe for the Frequency and Severity of the symptoms, respectively. The Global Score as reported in the Primary Outcome is obtained by taking the square root of the product of the frequency score multiplied by the severity score. A negative change from baseline indicates improvement. | Baseline to Day 15 |