Dry Eye
Conditions
Brief summary
To evaluate the tolerability and preliminary efficacy of Brimonidine eye drops (with and without corticosteroid eye drops) for the treatment of Dry Eye Disease (DED).
Detailed description
Subjects will assess their tolerance to the administration of the study drug, utilizing a Visual Analog Scale (VAS). The VAS is a 100-mm horizontal line with verbal descriptors at either end. The VAS ratings will be completed after administration of the study drug on Day 1 (post-dose), Day 28, Day 56, Day 84, and Day 105. Subjects will place a single slash mark across the horizontal line between the end labeled completely intolerable (0 mm) and easily tolerable (100mm).
Interventions
DRUGBrimonidine
Two products delivered in sequence twice daily.
DRUGBrimonidine Mono Therapy
Brimonidine given twice daily along with placebo drops
Placebo given twice daily.
DRUGCorticosteroid Eye Drop
Eye drop to be administered after Brimonidine in treatment arm 1
Sponsors
Ocugen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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 4. Objective evidence of DED in at least one eye by having 2 or more of the following 4 signs in the same eye at Screening and Baseline (Day 1) visits: i. Conjunctival staining at \>/= 1 (out of a possible score of 6 per eye) ii. Corneal staining at \>/= 2 (out of a possible score of 15 per eye) iii. Noninvasive Tear Break-Up Time (NITBUT) at \</= 7 seconds iv. Schirmer test at \<10mm in 5 minutes 5. Symptomatic evidence of DED by having a global symptom score (SANDE) \>/= 25 mm at both Screening and Baseline (Day 1) visits 6. Intraocular pressure (IOP) \>/= 5 mmHg and \</= 22 mmHg in each eye 7. Women who satisfy one of the following: 1. 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, OR 2. Are post-menopausal or have undergone a sterilization procedure
Exclusion criteria
1. Allergic to brimonidine, corticosteroids or any similar products, or excipients of brimonidine including benzalkonium chloride (BAK) 2. Use of contact lenses 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, institutionalized individuals, or others who may be considered vulnerable populations 13. Received corticosteroid-containing eye drops within the past 7 days or systemic corticosteroids/immunosuppressives within the past 3 months 14. Received cyclosporine ophthalmic emulsion 0.05% (Restasis®) or lifitegrast ophthalmic solution 5% (Xiidra™) within 30 days prior to Screening visit 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerance of Test Substance Visual Analogue Scale (VAS) Score | Days 1, 28, 56, and 84 | Participants assessed their tolerance to the administration of the study drug, utilizing a VAS. The VAS is a 100-mm horizontal line with verbal descriptors at either end. Participants placed a single slash mark across the horizontal line between the end labeled completely intolerable (0 mm) and easily tolerable (100mm). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Brimonidine and Corticosteroid Combination Therapy Brimonidine (0.2%) administered as eye drops, followed by loteprednol ophthalmic suspension (0.2%) BID for 12 weeks | 29 |
| Brimonidine Monotherapy Brimonidine (0.2%) administered as eye drops followed by placebo BID for 12 weeks | 28 |
| Placebo Sodium carboxymethylcellulose (0.25%) administered as eye drops followed by a second application BID for 12 weeks | 27 |
| Total | 84 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Brimonidine and Corticosteroid Combination Therapy | Brimonidine Monotherapy | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 62.1 years STANDARD_DEVIATION 11.41 | 60.4 years STANDARD_DEVIATION 13.88 | 59.2 years STANDARD_DEVIATION 14.23 | 60.6 years STANDARD_DEVIATION 13.09 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 25 Participants | 25 Participants | 79 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 28 Participants | 27 Participants | 26 Participants | 81 Participants |
| Sex: Female, Male Female | 26 Participants | 25 Participants | 18 Participants | 69 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants | 9 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 28 | 0 / 27 |
| other Total, other adverse events | 0 / 29 | 0 / 28 | 0 / 27 |
| serious Total, serious adverse events | 1 / 29 | 0 / 28 | 1 / 27 |
Outcome results
Primary
Tolerance of Test Substance Visual Analogue Scale (VAS) Score
Participants assessed their tolerance to the administration of the study drug, utilizing a VAS. The VAS is a 100-mm horizontal line with verbal descriptors at either end. Participants placed a single slash mark across the horizontal line between the end labeled completely intolerable (0 mm) and easily tolerable (100mm).
Time frame: Days 1, 28, 56, and 84
Population: Safety population that included all randomized participants who received at least one dose of study medication. Here, the overall number of participants analyzed are those evaluable for this Outcome Measure and the Number Analyzed per Row is the number of participants with evaluable data at each time point.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Brimonidine and Corticosteroid Combination Therapy | Tolerance of Test Substance Visual Analogue Scale (VAS) Score | Day 1 | 82.1 score on a scale |
| Brimonidine and Corticosteroid Combination Therapy | Tolerance of Test Substance Visual Analogue Scale (VAS) Score | Day 28 | 91.1 score on a scale |
| Brimonidine and Corticosteroid Combination Therapy | Tolerance of Test Substance Visual Analogue Scale (VAS) Score | Day 56 | 92.0 score on a scale |
| Brimonidine and Corticosteroid Combination Therapy | Tolerance of Test Substance Visual Analogue Scale (VAS) Score | Day 84 | 87.8 score on a scale |
| Brimonidine Monotherapy | Tolerance of Test Substance Visual Analogue Scale (VAS) Score | Day 84 | 85.9 score on a scale |
| Brimonidine Monotherapy | Tolerance of Test Substance Visual Analogue Scale (VAS) Score | Day 1 | 87.0 score on a scale |
| Brimonidine Monotherapy | Tolerance of Test Substance Visual Analogue Scale (VAS) Score | Day 56 | 85.6 score on a scale |
| Brimonidine Monotherapy | Tolerance of Test Substance Visual Analogue Scale (VAS) Score | Day 28 | 87.4 score on a scale |
| Placebo | Tolerance of Test Substance Visual Analogue Scale (VAS) Score | Day 84 | 94.8 score on a scale |
| Placebo | Tolerance of Test Substance Visual Analogue Scale (VAS) Score | Day 28 | 88.2 score on a scale |
| Placebo | Tolerance of Test Substance Visual Analogue Scale (VAS) Score | Day 56 | 91.0 score on a scale |
| Placebo | Tolerance of Test Substance Visual Analogue Scale (VAS) Score | Day 1 | 95.0 score on a scale |