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

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

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

Study Overview

• Status: Terminated
• Conditions: Dry Eye Disease
• Intervention / Treatment: Drug: P-321 Ophthalmic Solution; Drug: P-321 Ophthalmic Solution placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Artesia, California, United States, 90701
      • Sall Research Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Tauber Eye Center
    • Saint Louis, Missouri, United States, 63131
      • Ophthalmology Associates
    • Washington, Missouri, United States, 63090
      • Comprehensive Eye Care, Ltd.
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • UNC Kittner Eye Center
  • Texas
    • Houston, Texas, United States, 77030
      • Ocular Surface Center, Baylor College of Medicine
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Eye Consultants

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provide written informed consent
2. Male or female subjects aged 18 to 80 years, inclusive
3. Have a history of dry eye disease (DED) in both eyes
4. Be on stable regimens of other needed medications
5. Have a BCVA of +0.7 or better as assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS)
6. Have reported symptoms
7. 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.
8. Have normal lid anatomy

Exclusion Criteria:

1. Have undergone refractive eye surgery in the past 12 months
2. Have undergone previous eyelid surgery in either eye (External blepharoplasty not resulting in exposure or abnormal blinking is allowed)
3. Have lid irregularities or deformities
4. 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)
5. Have any clinically significant, uncontrolled, or unstable medical or surgical conditions that could affect his or her ability to participate
6. 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.
7. Have clinical findings of severe Meibomian Gland Dysfunction (MGD) in the Study Eye
8. Are pregnant or breast feeding
9. Use of any investigational product or device within 28 days prior to the Screening Visit or during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.017% P-321 Ophthalmic Solution; 0.017% P-321 Ophthalmic Solution TID for 28 days.	Drug: P-321 Ophthalmic Solution; P-321 Ophthalmic Solution 0.017%; Other Names: P-321
Placebo Comparator: Placebo; P-321 Ophthalmic Solution Placebo TID for 28 days.	Drug: P-321 Ophthalmic Solution placebo; Placebo to match P-321 Ophthalmic Solution; Other Names: Placebo

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Parion Sciences
• Investigators: Study Director: Jose Boyer, Parion Sciences

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: July 1, 2016
• First Submitted That Met QC Criteria: July 10, 2016
• First Posted (Estimate): July 13, 2016

Study Record Updates

• Last Update Posted (Actual): October 11, 2018
• Last Update Submitted That Met QC Criteria: September 12, 2018
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Ophthalmic Solutions; Pharmaceutical Solutions
• Other Study ID Numbers: P-321-202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No