Dry Eye Disease
Conditions
Keywords
Dry eye, ocular discomfort
Brief summary
The purpose of this study was to determine if difluprednate ophthalmic emulsion is effective in reducing the ocular symptoms of dry eye disease, as measured by a global Visual Analog Scale (VAS) discomfort score.
Detailed description
Following Run-In, patients qualifying for treatment were randomized 1:1 to receive Durezol (experimental group) or Vehicle (control group) for 5 weeks.
Interventions
Topical ocular steroid
OTHERDifluprednate vehicle
Inactive ingredients used as Run-In and placebo comparator
Sponsors
Alcon Research
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
Normal subjects: * No known history of dry eye disease. * Non-contact lens wearer. * No current use of artificial tears or any other dry eye treatment. OR Dry eye patients: * At least a 6 month history of dry eye. * Non-contact lens wearer. * Uses artificial tears. * Experiences persistent ocular discomfort. * Other protocol-defined inclusion criteria may apply.
Exclusion criteria
* The presence of any acute infectious or non-infectious ocular conditions in either eye within 1 month of Visit 1. * Severe Sjogren's Syndrome. * Lid function abnormalities. * Use of steroids, tetracycline, doxycycline, etc., within 30 days of Visit 1. * History of corneal surgery including refractive surgeries. * History of glaucoma or ocular hypertension * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline (Week 0) in Visual Analog Scale (VAS) Global Ocular Discomfort Score Over 4 Weeks | Baseline, up to 4 weeks | A Visual Analog Scale (VAS) was used by the subject to assess ocular discomfort, both frequency and severity, at baseline (pre-treatment) and weekly thereafter for 4 additional weeks. Each scale was 100 millimeters (mm) in length. The VAS score was calculated by measuring the length in mm from the start of the line to the intersection point of the vertical mark made by the subject. The Global Ocular Discomfort Score is a composite of the two VAS scores, ranging from 0 (very mildly) to 100 (very severely uncomfortable). |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from 25 investigative sites located within the US. Participant flow data is presented for all all subjects exposed to product.
Pre-assignment details
Of the 722 enrolled, 433 subjects did not qualify for Run-In and were exited without exposure to product. Of the 289 entering Run-In, 78 did not qualify for treatment. The 211 patients qualifying for treatment were randomized 1:1 to receive either Durezol or Vehicle.
Participants by arm
| Arm | Count |
|---|---|
| Run-In Only Difluprednate vehicle | 78 |
| Durezol Difluprednate vehicle (Run-in), followed by difluprednate 0.05% ophthalmic emulsion (treatment) | 107 |
| Vehicle Difluprednate vehicle (Run-In), followed by difluprednate vehicle (treatment) | 104 |
| Total | 289 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 4 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Other | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 0 |
| Overall Study | Pt Decision Unrelated to Adverse Event | 3 | 0 | 0 |
Baseline characteristics
| Characteristic | Run-In Only | Durezol | Vehicle | Total |
|---|---|---|---|---|
| Age Continuous | 61.9 years STANDARD_DEVIATION 12.7 | 54.4 years STANDARD_DEVIATION 14.8 | 60.1 years STANDARD_DEVIATION 13.8 | 58.5 years STANDARD_DEVIATION 14.2 |
| Region of Enrollment United States | 78 participants | 107 participants | 104 participants | 289 participants |
| Sex: Female, Male Female | 67 Participants | 90 Participants | 85 Participants | 242 Participants |
| Sex: Female, Male Male | 11 Participants | 17 Participants | 19 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 47 / 289 | 12 / 107 | 3 / 104 |
| serious Total, serious adverse events | 0 / 289 | 1 / 107 | 1 / 104 |
Outcome results
Primary
Mean Change From Baseline (Week 0) in Visual Analog Scale (VAS) Global Ocular Discomfort Score Over 4 Weeks
A Visual Analog Scale (VAS) was used by the subject to assess ocular discomfort, both frequency and severity, at baseline (pre-treatment) and weekly thereafter for 4 additional weeks. Each scale was 100 millimeters (mm) in length. The VAS score was calculated by measuring the length in mm from the start of the line to the intersection point of the vertical mark made by the subject. The Global Ocular Discomfort Score is a composite of the two VAS scores, ranging from 0 (very mildly) to 100 (very severely uncomfortable).
Time frame: Baseline, up to 4 weeks
Population: All subjects randomized to treatment and receiving at least 1 administration of study medication (ITT). Mixed model repeated measure (MMRM) approach was used to handle missing data during randomized treatment period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Durezol | Mean Change From Baseline (Week 0) in Visual Analog Scale (VAS) Global Ocular Discomfort Score Over 4 Weeks | Change from Baseline to Week 1 | -1.1 units on a scale | Standard Deviation 8.8 |
| Durezol | Mean Change From Baseline (Week 0) in Visual Analog Scale (VAS) Global Ocular Discomfort Score Over 4 Weeks | Change from Baseline to Week 3 | -4.5 units on a scale | Standard Deviation 13.4 |
| Durezol | Mean Change From Baseline (Week 0) in Visual Analog Scale (VAS) Global Ocular Discomfort Score Over 4 Weeks | Change from Baseline to Week 2 | -4.4 units on a scale | Standard Deviation 10.9 |
| Durezol | Mean Change From Baseline (Week 0) in Visual Analog Scale (VAS) Global Ocular Discomfort Score Over 4 Weeks | Change from Baseline to Week 4 | -6.2 units on a scale | Standard Deviation 15.1 |
| Durezol | Mean Change From Baseline (Week 0) in Visual Analog Scale (VAS) Global Ocular Discomfort Score Over 4 Weeks | Baseline (Week 0) | 78.3 units on a scale | Standard Deviation 14.4 |
| Vehicle | Mean Change From Baseline (Week 0) in Visual Analog Scale (VAS) Global Ocular Discomfort Score Over 4 Weeks | Change from Baseline to Week 4 | -4.7 units on a scale | Standard Deviation 16.1 |
| Vehicle | Mean Change From Baseline (Week 0) in Visual Analog Scale (VAS) Global Ocular Discomfort Score Over 4 Weeks | Baseline (Week 0) | 76.8 units on a scale | Standard Deviation 13.8 |
| Vehicle | Mean Change From Baseline (Week 0) in Visual Analog Scale (VAS) Global Ocular Discomfort Score Over 4 Weeks | Change from Baseline to Week 1 | -1.7 units on a scale | Standard Deviation 12.4 |
| Vehicle | Mean Change From Baseline (Week 0) in Visual Analog Scale (VAS) Global Ocular Discomfort Score Over 4 Weeks | Change from Baseline to Week 2 | -4.2 units on a scale | Standard Deviation 14.7 |
| Vehicle | Mean Change From Baseline (Week 0) in Visual Analog Scale (VAS) Global Ocular Discomfort Score Over 4 Weeks | Change from Baseline to Week 3 | -4.8 units on a scale | Standard Deviation 16.2 |