Dry Eye Syndromes
Conditions
Keywords
dry eye disease, reproxalap, Aldeyra, ADX-102
Brief summary
A Randomized, Double-Masked, Vehicle-Controlled Crossover Clinical Trial to Assess Efficacy and Safety of 0.25% Reproxalap Ophthalmic Solution Compared to Vehicle in Subjects with Dry Eye Disease
Interventions
Reproxalap Ophthalmic Solution (0.25%) dosed six times over two consecutive days
DRUGVehicle Ophthalmic Solution
Vehicle Ophthalmic Solution dosed six times over two consecutive days
Sponsors
Aldeyra Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Eighteen (18) to 70 years of age at the time of screening (either gender and any race) 2. Ability to provide written informed consent 3. Reported history of dry eye for at least 6 months prior to screening 4. Reported history of the use of eye drops for dry eye disease between 2 weeks to 6 months prior to screening
Exclusion criteria
1. Diagnosis of an ongoing ocular infection (bacterial, viral, or fungal), active ocular inflammation, or history of inflammatory disease (that, in the opinion of the Investigator, could interfere with study conduct or assessments) at screening 2. Contact lens use within 7 days of screening or anticipate using contact lenses during the trial 3. Systemic corticosteroid or other immunomodulatory therapy (not including inhaled corticosteroids) within 60 days of screening, or any planned immunomodulatory therapy throughout the study period 4. Women of childbearing potential (WOCBP) who are pregnant and nursing 5. If participant is of childbearing potential (female or male), unwillingness to use an acceptable means of birth control. 6. Known allergy and/or sensitivity to reproxalap or the drug product vehicle 7. A condition that the investigator feels may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the trial 8. Inability or unwillingness to follow instructions, including participation in all study assessments/procedures and visits
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Conjunctival Redness Assessed Via Digital Photography Over 90 Minutes in the Dry Eye Chamber | The efficacy assessment period was during a 90-minute dry eye chamber; baseline was pre-dose #1 for each treatment period. | Change from baseline comparison of reproxalap to vehicle for conjunctival redness assessed on a 0 to 4 scale (0 = none, 4 = extremely severe). The least squares mean (95% confidence interval) was derived from mixed model repeated measure for change from baseline included baseline as a covariate, and treatment, period, sequence, and time point as factors. |
| Schirmer Test Mean Change From Baseline | The efficacy assessment period was assessed on the first day of two consecutive dosing days for both crossover periods; baseline was pre-dose #1 for each treatment period. | Change from baseline comparison of reproxalap to vehicle for schirmer test on a millimeter line (0 = none, 35 = maximum). The least squares mean (95% confidence interval) was derived from mixed model repeated measure for change from baseline included baseline as a covariate, and treatment, period, sequence, and time point as factors. |
Countries
Canada
Participant flow
Pre-assignment details
Sixty-three subjects were randomized in a crossover design.
Participants by arm
| Arm | Count |
|---|---|
| Reproxalap (0.25%) First, Then Vehicle Subjects received reproxalap six times over two consecutive days, followed by a 7-day washout, then subjects received vehicle six times over two consecutive days. | 32 |
| Vehicle First, Then Reproxalap (0.25%) Subjects received vehicle six times over two consecutive days, followed by a 7-day washout, then subjects received reproxalap six times over two consecutive days. | 31 |
| Total | 63 |
Baseline characteristics
| Characteristic | Reproxalap (0.25%) First, Then Vehicle | Vehicle First, Then Reproxalap (0.25%) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants | 29 Participants | 59 Participants |
| Age, Continuous | 47.0 years STANDARD_DEVIATION 13.12 | 51.2 years STANDARD_DEVIATION 12.14 | 49.1 years STANDARD_DEVIATION 12.72 |
| Intraocular Pressure (left eye) | 11.7 mmHg STANDARD_DEVIATION 1.97 | 11.6 mmHg STANDARD_DEVIATION 2.61 | 11.6 mmHg STANDARD_DEVIATION 2.29 |
| Intraocular Pressure (right eye) | 11.6 mmHg STANDARD_DEVIATION 2.08 | 12.0 mmHg STANDARD_DEVIATION 2.76 | 11.8 mmHg STANDARD_DEVIATION 2.42 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 6 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 19 Participants | 43 Participants |
| Sex: Female, Male Female | 17 Participants | 24 Participants | 41 Participants |
| Sex: Female, Male Male | 15 Participants | 7 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 61 | 0 / 60 |
| other Total, other adverse events | 56 / 61 | 2 / 60 |
| serious Total, serious adverse events | 0 / 61 | 0 / 60 |
Outcome results
Primary
Conjunctival Redness Assessed Via Digital Photography Over 90 Minutes in the Dry Eye Chamber
Change from baseline comparison of reproxalap to vehicle for conjunctival redness assessed on a 0 to 4 scale (0 = none, 4 = extremely severe). The least squares mean (95% confidence interval) was derived from mixed model repeated measure for change from baseline included baseline as a covariate, and treatment, period, sequence, and time point as factors.
Time frame: The efficacy assessment period was during a 90-minute dry eye chamber; baseline was pre-dose #1 for each treatment period.
Population: Intent-to-treat population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Reproxalap (0.25%) | Conjunctival Redness Assessed Via Digital Photography Over 90 Minutes in the Dry Eye Chamber | 0.33 score on a scale |
| Vehicle | Conjunctival Redness Assessed Via Digital Photography Over 90 Minutes in the Dry Eye Chamber | 0.44 score on a scale |
Primary
Schirmer Test Mean Change From Baseline
Change from baseline comparison of reproxalap to vehicle for schirmer test on a millimeter line (0 = none, 35 = maximum). The least squares mean (95% confidence interval) was derived from mixed model repeated measure for change from baseline included baseline as a covariate, and treatment, period, sequence, and time point as factors.
Time frame: The efficacy assessment period was assessed on the first day of two consecutive dosing days for both crossover periods; baseline was pre-dose #1 for each treatment period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Reproxalap (0.25%) | Schirmer Test Mean Change From Baseline | -0.06 score on a scale |
| Vehicle | Schirmer Test Mean Change From Baseline | -2.54 score on a scale |