Dry Eye Syndromes
Conditions
Brief summary
This study will evaluate the safety, efficacy, tolerability, and systemic pharmacokinetics of 3 different doses of topical ophthalmic AGN-223575 suspension compared to AGN-223575 vehicle in patients with dry eye disease.
Interventions
DRUGAGN-223575 ophthalmic solution
AGN-223575 ophthalmic solution once or twice daily
DRUGAGN-223575 vehicle ophthalmic solution
Vehicle to AGN22375 ophthalmic solution once or twice daily.
Sponsors
Allergan
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
No
Inclusion criteria
* Signs and symptoms of dry eye disease * Has used RESTASIS and/or artificial tears in both eyes twice a day for at least 60 days.
Exclusion criteria
* History of glaucoma, or ocular hypertension * Diagnosis of ocular infection * Use of contact lenses in the past 14 days or expected use during the study * Use of any topical ophthalmic medications in the past 30 days * Use of corticosteroids in the past 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Conjunctival Redness Score in the Study Eye Using a 5-Point Scale | Baseline, Day 14 | Nasal and temporal bulbar conjunctival hyperemia were graded separately in each eye by the investigator under slit-lamp magnification by assigning a score of 0 to 4 for each quadrant based on comparison to the Allergan Dry Eye Redness Scale with photographic reference where: 0=Normal, vessels of bulbar conjunctiva are easily observed; 1=Trace redness; 2=Mild redness; 3=Moderate redness; 4=Severe redness, and each score is associated with a reference photo. For each eye, the study quadrant was determined by the greater (more severe) of the baseline redness scores for nasal and temporal bulbar conjunctival hyperemia as assessed using the Allergan Dry Eye Redness Scale. If the temporal score was greater than the nasal score, then the temporal quadrant was the study quadrant for the eye and was used to assess primary efficacy; otherwise the nasal quadrant was the study quadrant. A negative change from baseline (less redness) indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Ocular Surface Disease Index (OSDI) Total Score Using a 5-Point Scale | Baseline, Day 14 | OSDI questionnaire consists of 12 questions regarding ocular symptoms, environmental triggers, and vision-related functioning in patients with dry eye disease. The participants rate each question on a 5-point scale where: 0=none of the time to 4=all of the time. The scores are totaled over the 12 questions and normalized/converted to a total score of 0=no disability to 100=complete disability. Higher OSDI scores are associated with greater severity. A negative change from Baseline indicates improvement. |
| Change From Baseline in Corneal Staining Score of the Study Eye Using a 6-Point Scale | Baseline, Day 14 | The cornea is the transparent front part of the eye which covers the iris and pupil. Staining of the cornea following ocular administration of fluorescein dye was graded using a 6-point scale where: 0=no staining to 5=diffuse staining. The higher the grade score, the worse the dry eye severity. A negative change from Baseline indicates improvement. |
| Percentage of Participants With Complete Redness Response (Yes/No) in the Study Eye | Day 14 | A participant was considered a redness responder if the study quadrant redness score based on the Allergan Dry Eye Redness Scale in the study eye was 0=Normal (no redness). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AGN-223575 Dose A 1 drop of AGN-223575 Dose A ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose A ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days. | 58 |
| AGN-223575 Dose B 1 drop of AGN-223575 Dose B ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose B ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days. | 59 |
| AGN-223575 Dose C 1 drop of AGN-223575 Dose C ophthalmic solution administered in each eye twice daily for 14 day followed by either 1 drop of AGN-223575 Dose C ophthalmic solution or 1 drop of vehicle to AGN-223575 in each eye once daily for 7 days. | 60 |
| AGN-223575 Vehicle 1 drop of Vehicle to AGN-223575 ophthalmic solution administered in each eye twice daily for 14 day followed by 1 drop of vehicle to AGN-223575 ophthalmic solution in each eye once daily for 7 days. | 59 |
| Total | 236 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Ocular Adverse Event | 1 | 0 | 0 | 0 |
| Overall Study | Other Miscellaneous Reason | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | AGN-223575 Dose A | AGN-223575 Dose B | AGN-223575 Dose C | AGN-223575 Vehicle | Total |
|---|---|---|---|---|---|
| Age, Continuous | 53.9 years STANDARD_DEVIATION 16.37 | 59.2 years STANDARD_DEVIATION 14.74 | 56.6 years STANDARD_DEVIATION 16.1 | 54.1 years STANDARD_DEVIATION 17.87 | 56.0 years STANDARD_DEVIATION 16.34 |
| Sex: Female, Male Female | 36 Participants | 47 Participants | 39 Participants | 46 Participants | 168 Participants |
| Sex: Female, Male Male | 22 Participants | 12 Participants | 21 Participants | 13 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 58 | 4 / 59 | 4 / 60 | 6 / 59 |
| serious Total, serious adverse events | 1 / 58 | 1 / 59 | 1 / 60 | 0 / 59 |
Outcome results
Primary
Change From Baseline in Conjunctival Redness Score in the Study Eye Using a 5-Point Scale
Nasal and temporal bulbar conjunctival hyperemia were graded separately in each eye by the investigator under slit-lamp magnification by assigning a score of 0 to 4 for each quadrant based on comparison to the Allergan Dry Eye Redness Scale with photographic reference where: 0=Normal, vessels of bulbar conjunctiva are easily observed; 1=Trace redness; 2=Mild redness; 3=Moderate redness; 4=Severe redness, and each score is associated with a reference photo. For each eye, the study quadrant was determined by the greater (more severe) of the baseline redness scores for nasal and temporal bulbar conjunctival hyperemia as assessed using the Allergan Dry Eye Redness Scale. If the temporal score was greater than the nasal score, then the temporal quadrant was the study quadrant for the eye and was used to assess primary efficacy; otherwise the nasal quadrant was the study quadrant. A negative change from baseline (less redness) indicates improvement.
Time frame: Baseline, Day 14
Population: Modified Intent-to-treat (mITT) population, consisted of all randomized and treated patients who had a baseline and at least 1 post-baseline assessment of nasal or temporal redness using the Allergan Dry Eye Redness Scale. n in the category is the number of participants with data available at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AGN-223575 Dose A | Change From Baseline in Conjunctival Redness Score in the Study Eye Using a 5-Point Scale | Baseline | 1.9 score on a scale | Standard Deviation 0.68 |
| AGN-223575 Dose A | Change From Baseline in Conjunctival Redness Score in the Study Eye Using a 5-Point Scale | Change from Baseline at Day 14 | -0.7 score on a scale | Standard Deviation 0.8 |
| AGN-223575 Dose B | Change From Baseline in Conjunctival Redness Score in the Study Eye Using a 5-Point Scale | Change from Baseline at Day 14 | -0.9 score on a scale | Standard Deviation 0.76 |
| AGN-223575 Dose B | Change From Baseline in Conjunctival Redness Score in the Study Eye Using a 5-Point Scale | Baseline | 2.2 score on a scale | Standard Deviation 0.69 |
| AGN-223575 Dose C | Change From Baseline in Conjunctival Redness Score in the Study Eye Using a 5-Point Scale | Baseline | 2.0 score on a scale | Standard Deviation 0.7 |
| AGN-223575 Dose C | Change From Baseline in Conjunctival Redness Score in the Study Eye Using a 5-Point Scale | Change from Baseline at Day 14 | -0.8 score on a scale | Standard Deviation 0.76 |
| AGN-223575 Vehicle | Change From Baseline in Conjunctival Redness Score in the Study Eye Using a 5-Point Scale | Baseline | 2.1 score on a scale | Standard Deviation 0.72 |
| AGN-223575 Vehicle | Change From Baseline in Conjunctival Redness Score in the Study Eye Using a 5-Point Scale | Change from Baseline at Day 14 | -0.6 score on a scale | Standard Deviation 0.84 |
Secondary
Change From Baseline in Corneal Staining Score of the Study Eye Using a 6-Point Scale
The cornea is the transparent front part of the eye which covers the iris and pupil. Staining of the cornea following ocular administration of fluorescein dye was graded using a 6-point scale where: 0=no staining to 5=diffuse staining. The higher the grade score, the worse the dry eye severity. A negative change from Baseline indicates improvement.
Time frame: Baseline, Day 14
Population: mITT population, consisted of all randomized and treated participants who had a baseline and at least 1 post-baseline assessment of nasal or temporal redness using the Allergan Dry Eye Redness Scale. n in the category is the number of participants with data available at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AGN-223575 Dose A | Change From Baseline in Corneal Staining Score of the Study Eye Using a 6-Point Scale | Baseline | 1.7 score on a scale | Standard Deviation 0.76 |
| AGN-223575 Dose A | Change From Baseline in Corneal Staining Score of the Study Eye Using a 6-Point Scale | Change from Baseline at Day 14 | -0.6 score on a scale | Standard Deviation 0.82 |
| AGN-223575 Dose B | Change From Baseline in Corneal Staining Score of the Study Eye Using a 6-Point Scale | Change from Baseline at Day 14 | -0.6 score on a scale | Standard Deviation 0.8 |
| AGN-223575 Dose B | Change From Baseline in Corneal Staining Score of the Study Eye Using a 6-Point Scale | Baseline | 1.9 score on a scale | Standard Deviation 0.85 |
| AGN-223575 Dose C | Change From Baseline in Corneal Staining Score of the Study Eye Using a 6-Point Scale | Baseline | 1.8 score on a scale | Standard Deviation 0.88 |
| AGN-223575 Dose C | Change From Baseline in Corneal Staining Score of the Study Eye Using a 6-Point Scale | Change from Baseline at Day 14 | -0.6 score on a scale | Standard Deviation 0.97 |
| AGN-223575 Vehicle | Change From Baseline in Corneal Staining Score of the Study Eye Using a 6-Point Scale | Baseline | 1.8 score on a scale | Standard Deviation 0.75 |
| AGN-223575 Vehicle | Change From Baseline in Corneal Staining Score of the Study Eye Using a 6-Point Scale | Change from Baseline at Day 14 | -0.5 score on a scale | Standard Deviation 0.89 |
Secondary
Change From Baseline in Ocular Surface Disease Index (OSDI) Total Score Using a 5-Point Scale
OSDI questionnaire consists of 12 questions regarding ocular symptoms, environmental triggers, and vision-related functioning in patients with dry eye disease. The participants rate each question on a 5-point scale where: 0=none of the time to 4=all of the time. The scores are totaled over the 12 questions and normalized/converted to a total score of 0=no disability to 100=complete disability. Higher OSDI scores are associated with greater severity. A negative change from Baseline indicates improvement.
Time frame: Baseline, Day 14
Population: mITT population, consisted of all randomized and treated participants who had a baseline and at least 1 post-baseline assessment of nasal or temporal redness using the Allergan Dry Eye Redness Scale. n in the category is the number of participants with data available at the given time-point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AGN-223575 Dose A | Change From Baseline in Ocular Surface Disease Index (OSDI) Total Score Using a 5-Point Scale | Baseline | 49.65 score on a scale | Standard Deviation 16.51 |
| AGN-223575 Dose A | Change From Baseline in Ocular Surface Disease Index (OSDI) Total Score Using a 5-Point Scale | Change from Baseline at Day 14 | -14.64 score on a scale | Standard Deviation 16.647 |
| AGN-223575 Dose B | Change From Baseline in Ocular Surface Disease Index (OSDI) Total Score Using a 5-Point Scale | Change from Baseline at Day 14 | -15.92 score on a scale | Standard Deviation 16.329 |
| AGN-223575 Dose B | Change From Baseline in Ocular Surface Disease Index (OSDI) Total Score Using a 5-Point Scale | Baseline | 51.00 score on a scale | Standard Deviation 18.908 |
| AGN-223575 Dose C | Change From Baseline in Ocular Surface Disease Index (OSDI) Total Score Using a 5-Point Scale | Baseline | 48.95 score on a scale | Standard Deviation 16.472 |
| AGN-223575 Dose C | Change From Baseline in Ocular Surface Disease Index (OSDI) Total Score Using a 5-Point Scale | Change from Baseline at Day 14 | -15.27 score on a scale | Standard Deviation 17.305 |
| AGN-223575 Vehicle | Change From Baseline in Ocular Surface Disease Index (OSDI) Total Score Using a 5-Point Scale | Baseline | 52.63 score on a scale | Standard Deviation 19.204 |
| AGN-223575 Vehicle | Change From Baseline in Ocular Surface Disease Index (OSDI) Total Score Using a 5-Point Scale | Change from Baseline at Day 14 | -14.76 score on a scale | Standard Deviation 17.297 |
Secondary
Percentage of Participants With Complete Redness Response (Yes/No) in the Study Eye
A participant was considered a redness responder if the study quadrant redness score based on the Allergan Dry Eye Redness Scale in the study eye was 0=Normal (no redness).
Time frame: Day 14
Population: Participants from the mITT population, all randomized and treated participants who had a baseline and at least 1 post-baseline assessment of nasal or temporal redness using the Allergan Dry Eye Redness Scale. with data available for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AGN-223575 Dose A | Percentage of Participants With Complete Redness Response (Yes/No) in the Study Eye | Yes | 10.7 percentage of participants |
| AGN-223575 Dose A | Percentage of Participants With Complete Redness Response (Yes/No) in the Study Eye | No | 89.3 percentage of participants |
| AGN-223575 Dose B | Percentage of Participants With Complete Redness Response (Yes/No) in the Study Eye | No | 87.9 percentage of participants |
| AGN-223575 Dose B | Percentage of Participants With Complete Redness Response (Yes/No) in the Study Eye | Yes | 12.1 percentage of participants |
| AGN-223575 Dose C | Percentage of Participants With Complete Redness Response (Yes/No) in the Study Eye | Yes | 15.0 percentage of participants |
| AGN-223575 Dose C | Percentage of Participants With Complete Redness Response (Yes/No) in the Study Eye | No | 85.0 percentage of participants |
| AGN-223575 Vehicle | Percentage of Participants With Complete Redness Response (Yes/No) in the Study Eye | Yes | 10.5 percentage of participants |
| AGN-223575 Vehicle | Percentage of Participants With Complete Redness Response (Yes/No) in the Study Eye | No | 89.5 percentage of participants |