Study of Brimonidine Tartrate Nanoemulsion Eye Drop Solution in the Treatment of Dry Eye Disease (DED)

A Phase 3 Randomized, Placebo-Controlled, Double-Masked, Multicenter, Safety and Efficacy Study of Brimonidine Tartrate 0.2% Nanoemulsion Eye Drops in Patients With Dry Eye Disease (DED)

This study evaluates the use of Brimonidine tartrate nanoemulsion eye drop solution in the treatment of Dry Eye Disease (DED). Half of participants will receive Brimonidine and half will receive ophthalmic buffered saline (placebo).

Study Overview

• Status: Completed
• Conditions: Dry Eye
• Intervention / Treatment: Drug: Brimonidine Tartrate; Drug: Placebos

Detailed Description

Dry eye disease (DED) is a common ocular disorder involving the aberrant production and instability of tear film, which results in damage to the ocular surface and is correlated with symptoms of ocular discomfort.

This study will be a randomized, placebo-controlled, double-masked, multicenter phase 3 study in the United States conducted at approximately 25 centers. Upon meeting the eligibility criteria, enrolled subjects will be randomly assigned in a 1:1 (test:control) fashion to receive either Brimonidine Nanoemulsion Eye Drops 0.20% investigational product (test) or ophthalmic buffered saline (placebo).

• Study Type: Interventional
• Enrollment (Actual): 252
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Newport Beach, California, United States, 92663
      • Aesthetic Eye Care Institute/David Wirta, MD and Associates
    • Rancho Cordova, California, United States, 95670
      • Martel Medical Eye Group
  • Florida
    • Pompano Beach, Florida, United States, 33064
      • Rand Eye Institute
  • Illinois
    • Hoffman Estates, Illinois, United States, 60169
      • Chicago Cornea Consultants
  • Kansas
    • Mission, Kansas, United States, 66204
      • Heart of America Eye Care, P. A.
  • Missouri
    • Saint Louis, Missouri, United States, 63131
      • Ophthalmology Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45236
      • Apex Eye- Kenwood
    • Cincinnati, Ohio, United States, 45242
      • Apex Eye-Montgomery
    • Cleveland, Ohio, United States, 44115
      • Abrams Eye Center
  • Pennsylvania
    • Cranberry Township, Pennsylvania, United States, 16066
      • Scott and Christie Eyecare Associates
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Total Eye Care
    • Nashville, Tennessee, United States, 37215
      • Toyos Clinic
  • Texas
    • Houston, Texas, United States, 77004
      • Midtown Eye Physicans & Associates
    • Houston, Texas, United States, 77034
      • Advanced Laser Vision & Surgical Institute
    • Lakeway, Texas, United States, 78734
      • Revolution Research, Inc; Lake Travis Eye and Laser Center
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • The Eye Institute of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged 18 years or older.
2. Sign and date informed consent form approved by the IRB
3. History of Dry Eye Disease for ≥6 months

4. Demonstrate the following 2 signs of DED in the same eye at Screening and Baseline (Day 1):

   1. Conjunctival staining at ≥3 (out of a possible score of 6 per eye), and
   2. Schirmer test (with anesthesia) at ≥1 to ≤7mm in 5 minutes
5. Symptomatic evidence of DED by having a global symptom score (Overall SANDE) ≥40 mm at Screening and Baseline (Day 1) visit
6. Intraocular pressure (IOP) ≥ 5 mmHg and ≤22 mmHg in each eye
7. Women who satisfy one of the following:

8a. Are of child-bearing potential (WOCP) who are not pregnant or lactating and who are either abstinent or sexually active on an acceptable method of birth control for at least 4 weeks prior to Visit 1 and throughout the study (i.e., until Day 28), OR 8b. Are post-menopausal or have undergone a sterilization procedure

Exclusion Criteria:

1. Allergic to brimonidine or any similar products, or excipients of brimonidine
2. Use of contact lenses within 14 days prior to Screening visit or planned use during study
3. Currently receiving brimonidine or other treatment for glaucoma or ocular hypertension or history of glaucoma surgery.
4. Receiving or have received any experimental or investigational drug or device within 30 days prior to Screening visit
5. Intraocular pressure <5 mmHg or >22 mmHg in either eye
6. Active ocular infection or history of ocular herpetic keratitis
7. History of neurotrophic keratitis or ocular neuropathic pain
8. Any history of eyelid surgery or intraocular/ocular surgery within the past 3 months
9. Punctal occlusion within 3 months prior to Screening visit or during study
10. Corneal epithelial defect larger than 1 mm2 in either eye
11. Have active drug/alcohol dependence or abuse history
12. Are neonates, pregnant/lactating women, children, or others who may be considered vulnerable populations
13. Received corticosteroid-containing eye drops within 14 days prior to Screening visit or planned use during study
14. Any change in systemic corticosteroids/immunosuppressives, cyclosporine ophthalmic emulsion 0.05% (Restasis®), cyclosporine ophthalmic solution 0.09% (Cequa™), or lifitegrast ophthalmic solution 5% (Xiidra®) within 30 days prior to Screening visit or planned change during study
15. In the opinion of Investigator or Study Coordinator, be unwilling or unable to comply with study protocol or unable to successfully instill eye drops
16. Disease, condition, or disorder that in the judgement of Investigator could confound study assessments or limit compliance to study protocol

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OCU-310; Brimonidine Tartrate Nanoemulsion Eye Drops 0.20% given 2 times a day for 4 weeks	Drug: Brimonidine Tartrate; Brimonidine Tartrate Nanoemulsion Eye Drops 0.20% given 2 times a day for 4 weeks.; Other Names: OCU-310
Placebo Comparator: Placebos; Ophthalmic buffered saline Eye Drops given 2 times a day for 4 weeks	Drug: Placebos; Ophthalmic buffered saline Eye Drops given 2 times a day for 4 weeks.; Other Names: Ophthalmic buffered saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to 4 Weeks (Day 28) in Symptom Assessment in Dry Eye (SANDE) Questionnaire Score	The SANDE questionnaire is a short Visual Analog Scale (VAS) assessment that quantifies both severity and frequency of current dry eye symptoms. The SANDE is comprised of two questions, and each question employs a 100-mm horizontal linear VAS. The measurement of symptom frequency ranges from "rarely" to "all of the time", and the symptom severity from "very mild" to "very severe". Data collected from the SANDE questionnaire was calculated by multiplying the frequency score by the severity score and obtaining the square root. The result is the Overall SANDE score which ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.	Baseline, 4 weeks (Day 28)
Change From Baseline to 4 Weeks (Day 28) in Lissamine Green Conjunctival Staining Scores	Conjunctival staining with Lissamine Green dye (1%; LG) staining in each eye was conducted using the slit lamp. A single drop of 1% Lissamine Green dye was applied to the inferior conjunctival fornix of both eyes. The conjunctivae was examined with the slit lamp at ×10 magnification, using a neutral-density filter. The conjunctiva was graded for each eye from 0 to 3 based on the density of punctate staining in the nasal-bulbar and temporal-bulbar zones. Total scores ranged from 0 (no staining) to 6 (most severe staining) with a lower score representing a more desirable outcome.	Baseline, 4 Weeks (Day 28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to 2 Weeks (Day 14) in SANDE Score	The SANDE questionnaire is a short Visual Analog Scale (VAS) assessment that quantifies both severity and frequency of current dry eye symptoms. The SANDE is comprised of two questions, and each question employs a 100-mm horizontal linear VAS. The measurement of symptom frequency ranges from "rarely" to "all of the time", and the symptom severity from "very mild" to "very severe". Data collected from the SANDE questionnaire was calculated by multiplying the frequency score by the severity score and obtaining the square root. The result is the Overall SANDE score which ranges from 0 to 100 with 100 being the maximal amount of dry eye symptoms and 0 being the minimal amount of dry eye symptoms.	Baseline, 2 weeks (Day 14)
Change From Baseline to 2 Weeks (Day 14) in Lissamine Green Conjunctival Staining Scores	Conjunctival staining with Lissamine Green dye (1%; LG) staining in each eye was conducted using the slit lamp. A single drop of 1% Lissamine Green dye was applied to the inferior conjunctival fornix of both eyes. The conjunctivae was examined with the slit lamp at ×10 magnification, using a neutral-density filter. The conjunctiva was graded for each eye from 0 to 3 based on the density of punctate staining in the nasal-bulbar and temporal-bulbar zones. Total scores ranged from 0 (no staining) to 6 (most severe staining) with a lower score representing a more desirable outcome.	Baseline, 2 Weeks (Day 14)

Collaborators and Investigators

• Sponsor: Ocugen

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2018
• Primary Completion (Actual): February 25, 2019
• Study Completion (Actual): February 25, 2019

Study Registration Dates

• First Submitted: December 20, 2018
• First Submitted That Met QC Criteria: December 20, 2018
• First Posted (Actual): December 24, 2018

Study Record Updates

• Last Update Posted (Actual): July 18, 2022
• Last Update Submitted That Met QC Criteria: June 29, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Dry Eye Disease
• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Brimonidine Tartrate
• Other Study ID Numbers: OCU-310-301

Drug and device information, study documents

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