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

Dry Eye Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03785340
• Other study ID #: OCU-310-301
• Status: Completed
• Phase: Phase 3
• Start date: December 3, 2018
• Est. completion date: February 25, 2019

Study information

• Verified date: June 2022
• Source: Ocugen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 252
• Est. completion date: February 25, 2019
• Est. primary completion date: February 25, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Dry Eye
• Dry Eye Syndromes
• Eye Diseases
• Keratoconjunctivitis Sicca

Intervention

Drug:
• Brimonidine Tartrate
Brimonidine Tartrate Nanoemulsion Eye Drops 0.20% given 2 times a day for 4 weeks.
• Placebos
Ophthalmic buffered saline Eye Drops given 2 times a day for 4 weeks.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Ocugen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	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)
Secondary	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)