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

• ClinicalTrials.gov Identifier: NCT03785340
• Recruitment Status: Completed
• First Posted: December 24, 2018
• Results First Posted: June 6, 2022
• Last Update Posted: June 30, 2022
• Sponsor: Ocugen
• Information provided by (Responsible Party): Ocugen

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Dry Eye	Drug: Brimonidine Tartrate; Drug: Placebos	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 252 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: December 3, 2018
• Actual Primary Completion Date: February 25, 2019
• Actual Study Completion Date: February 25, 2019

Arms and Interventions

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 Name: 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 Name: Ophthalmic buffered saline solution

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline to 4 Weeks (Day 28) in Symptom Assessment in Dry Eye (SANDE) Questionnaire Score [ Time Frame: Baseline, 4 weeks (Day 28) ]
   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.
2. Change From Baseline to 4 Weeks (Day 28) in Lissamine Green Conjunctival Staining Scores [ Time Frame: Baseline, 4 Weeks (Day 28) ]
   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.

Secondary Outcome Measures :

1. Change From Baseline to 2 Weeks (Day 14) in SANDE Score [ Time Frame: Baseline, 2 weeks (Day 14) ]
   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.
2. Change From Baseline to 2 Weeks (Day 14) in Lissamine Green Conjunctival Staining Scores [ Time Frame: Baseline, 2 Weeks (Day 14) ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Aesthetic Eye Care Institute/David Wirta, MD and Associates

Newport Beach, California, United States, 92663

Martel Medical Eye Group

Rancho Cordova, California, United States, 95670

United States, Florida

Rand Eye Institute

Pompano Beach, Florida, United States, 33064

United States, Illinois

Chicago Cornea Consultants

Hoffman Estates, Illinois, United States, 60169

United States, Kansas

Heart of America Eye Care, P. A.

Mission, Kansas, United States, 66204

United States, Missouri

Ophthalmology Associates

Saint Louis, Missouri, United States, 63131

United States, Ohio

Apex Eye- Kenwood

Cincinnati, Ohio, United States, 45236

Apex Eye-Montgomery

Cincinnati, Ohio, United States, 45242

Abrams Eye Center

Cleveland, Ohio, United States, 44115

United States, Pennsylvania

Scott and Christie Eyecare Associates

Cranberry Township, Pennsylvania, United States, 16066

United States, Tennessee

Total Eye Care

Memphis, Tennessee, United States, 38119

Toyos Clinic

Nashville, Tennessee, United States, 37215

United States, Texas

Midtown Eye Physicans & Associates

Houston, Texas, United States, 77004

Advanced Laser Vision & Surgical Institute

Houston, Texas, United States, 77034

Revolution Research, Inc; Lake Travis Eye and Laser Center

Lakeway, Texas, United States, 78734

United States, Utah

The Eye Institute of Utah

Salt Lake City, Utah, United States, 84107

Sponsors and Collaborators

Ocugen

  Study Documents (Full-Text)

Documents provided by Ocugen:

Study Protocol, Statistical Analysis Plan, and Informed Consent Form  [PDF] August 12, 2018

More Information

• Responsible Party: Ocugen
• ClinicalTrials.gov Identifier: NCT03785340
• Other Study ID Numbers: OCU-310-301
• First Posted: December 24, 2018
• Results First Posted: June 6, 2022
• Last Update Posted: June 30, 2022
• Last Verified: June 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ocugen:

Dry Eye Disease

Additional relevant MeSH terms:

Dry Eye Syndromes; Keratoconjunctivitis Sicca; Eye Diseases; Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Brimonidine Tartrate; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs