Dry Eye Disease
Conditions
Brief summary
This is a Phase 2b, multicenter, vehicle-controlled, double-masked, randomized study. All subjects enrolled will have dry eye disease. The study consists of Screening and Baseline visits to determine eligibility, followed by efficacy assessments at Day 14 (Visit 3), 28 (Visit 4) and 84 (Visit 5/Study Exit). Safety will be assessed at all study visits.
Detailed description
At the end of the Screening Visit, all qualified subjects will be assigned to administer AR-15512 vehicle twice a day to both eyes for 14 days (vehicle run-in period). After the vehicle run-in period, subjects will be re-evaluated for signs and symptoms of Dry Eye Disease (DED). Subjects who requalify based on inclusion/exclusion criteria will be randomized in a 1:1:1 ratio to receive AR-15512 0.0014% (lower dose), AR-15512 0.003% (higher dose) or AR-15512 vehicle administered as 1 drop in each eye twice daily for 84 days. This study will utilize a Controlled Adverse Environment (CAE) chamber, which serves to (1) minimize the factors that could impact the evaluation (temperature, humidity, and airflow) and (2) stress the ocular surface in a safe, standardized, controlled, and reproducible manner. Subjects will be exposed to the CAE for approximately 90 minutes during each CAE visit. Subjects will be exposed to the CAE at the Screening and Baseline visits as well as on Day 28 (Visit 4) and Day 84 (Visit 5). Efficacy endpoints will be evaluated pre- and post- exposure to the CAE. Aerie Pharmaceuticals was acquired by Alcon on November 22, 2022.
Interventions
DRUGAR-15512 Ophthalmic Solution
Ophthalmic solution administered via topical ocular instillation in one of two dose concentrations: 0.0014% (lower dose) or 0.003% (higher dose)
DRUGAR-15512 Ophthalmic Solution Vehicle
Ophthalmic solution vehicle administered via topical ocular instillation
Sponsors
Aerie Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Previous history of dry eye disease (DED) within the previous 6 months; * Have used and/or desired to use artificial tears for DED symptoms within 2 months prior to the Screening visit; * Signs and symptoms of DED at the Screening and Baseline visits; * Best Corrected Visual Acuity (BCVA) of 20/200 (+0.70 LogMAR) or better in both eyes at both the Screening and Baseline visits; * Other protocol-specified inclusion criteria may apply. Key
Exclusion criteria
* History or presence of any ocular disorder or condition (other than DED) in either eye that would, in the opinion of the investigator, likely interfere with the interpretation of the study results or subject safety; * Current evidence of other significant ophthalmic diseases which, in the opinion of the investigator, may interfere with study findings or interpretation; * Use of contact lenses in either eye within 7 days prior to the Screening visit or planned use during the study; * Regular use of ocular medications or nutritional supplements as specified in the protocol within 30 days prior to the Screening visit; * Positive pregnancy test at Screening or Baseline visits or currently breastfeeding. * Other protocol-specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Mean Change From Baseline in Pre-CAE (Controlled Adverse Environment) Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 28 | Baseline (Day 1) (pre-treatment), Day 28 | Ocular discomfort was assessed using a Visual Analogue Scale (VAS) that ranged from 0 millimeters (mm) (no ocular discomfort) to 100 mm (maximum ocular discomfort). Ocular discomfort was assessed at Baseline prior to CAE exposure and at Day 28 prior to CAE exposure. The Day 28 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. This is a co-primary endpoint. |
| Least Squares Mean Change From Baseline in Pre-CAE Anesthetized Schirmer Test Score at Day 28 | Baseline (Day 1) (pre-treatment), Day 28 | The Schirmer test measures tear production. Following instillation of topical anesthetic drops, Schirmer strips were placed on the lower eye lids, eyes were closed, and strips remained in place for 5 minutes or until both strips reached a maximum score. The strips were removed, and the amount of wetting was recorded on a scale from 0 mm (no tear production) to 35 mm (maximum tear production). The test was performed at Baseline prior to CAE exposure and at Day 28 prior to CAE exposure. The Day 28 value was subtracted from the Baseline value. A more positive change value indicates a better outcome. One eye (study eye) contributed data to the analysis. This is a co-primary endpoint. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 84 | Day 84 | Ocular discomfort was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular discomfort) to 100 mm (maximum ocular discomfort) prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Change From Baseline in Pre-CAE Anesthetized Schirmer Test Score at Day 84 | Baseline (Day 1) (pre-treatment), Day 84 | The Schirmer test measures tear production. Following instillation of topical anesthetic drops, Schirmer strips were the placed on the lower eye lids, eyes were closed, and strips remained in place for 5 minutes or until both strips reached a maximum score. The strips were removed, and the amount of wetting was recorded on a scale from 0 mm (no tear production) to 35 mm (maximum tear production). The test was performed at Baseline prior to CAE exposure and at Day 84 prior to CAE exposure. The Day 84 value was subtracted from the Baseline value. A more positive change value indicates a better outcome. One eye (study eye) contributed data to the analysis. |
| Least Squares Mean Pre-CAE Anesthetized Schirmer Test Score at Day 84 | Day 84 | The Schirmer test measures tear production. Following instillation of topical anesthetic drops, Schirmer strips were the placed on the lower eye lids, eyes were closed, and strips remained in place for 5 minutes or until both strips reached a maximum score. The strips were removed, and the amount of wetting was recorded on a scale from 0 mm (no tear production) to 35 mm (maximum tear production). A higher score indicates a better outcome. The test was performed prior to CAE exposure. One eye (study eye) contributed data to the analysis. |
| Least Squares Mean Pre-CAE Anesthetized Schirmer Test Score at Day 28 | Day 28 | The Schirmer test measures tear production. Following instillation of topical anesthetic drops, Schirmer strips were the placed on the lower eye lids, eyes were closed, and strips remained in place for 5 minutes or until both strips reached a maximum score. The strips were removed, and the amount of wetting was recorded on a scale from 0 mm (no tear production) to 35 mm (maximum tear production). A higher score indicates a better outcome. The test was performed prior to CAE exposure. One eye (study eye) contributed data to the analysis. |
| Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 84 | Baseline (Day 1) (pre-treatment), Day 84 | Ocular pain was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain). Ocular pain was assessed at Baseline prior to CAE exposure and at Day 84 prior to CAE exposure. The Day 84 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 84 | Day 84 | Ocular pain was assessed prior to CAE exposure using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain) prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 28 | Baseline (Day 1) (pre-treatment), Day 28 | Ocular pain was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain). Ocular pain was assessed at Baseline prior to CAE exposure and at Day 28 prior to CAE exposure. The Day 28 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 28 | Day 28 | Ocular pain was assessed prior to CAE exposure using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain) prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Change From Baseline in Post-CAE Pain Score on a Visual Analogue Scale at Day 84 | Baseline (Day 1) (pre-treatment), Day 84 | Ocular pain was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain). Ocular pain was assessed at Baseline prior to CAE exposure and at Day 84 following CAE exposure. The Day 84 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Post-CAE Pain Score on a Visual Analogue Scale at Day 84 | Day 84 | Ocular pain was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain) following CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Change From Baseline in Post-CAE Pain Score on a Visual Analogue Scale at Day 28 | Baseline (Day 1) (pre-treatment), Day 28 | Ocular pain was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain). Ocular pain was assessed at Baseline prior to CAE exposure and at Day 28 following CAE exposure. The Day 28 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Post-CAE Pain Score on a Visual Analogue Scale at Day 28 | Day 28 | Ocular pain was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain) following CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 28 | Baseline (Day 1) (pre-treatment), Day 28 | The SANDE questionnaire assesses the frequency and severity of dry eye disease symptoms. Subjects used 2 unique, 100 mm Visual Analogue Scales (VAS) to mark the frequency of symptoms (0=rarely, 100=all the time) and the severity of symptoms (0=very mild, 100=very severe) for both eyes together. The Global SANDE score was calculated by multiplying the frequency score by the severity score and obtaining the square root. The final value was rounded nearest whole number. The SANDE questionnaire was completed at Baseline prior to CAE exposure and at Day 28 prior to CAE exposure. The Day 28 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 28 | Day 28 | The SANDE questionnaire assesses the frequency and severity of dry eye disease symptoms. Subjects used 2 unique, 100 mm Visual Analogue Scales (VAS) to mark the frequency of symptoms (0=rarely, 100=all the time) and the severity of symptoms (0=very mild, 100=very severe) for both eyes together. The Global SANDE score was calculated by multiplying the frequency score by the severity score and obtaining the square root. The final value was rounded nearest whole number. The SANDE questionnaire was completed prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 84 | Baseline (Day 1) (pre-treatment), Day 84 | The SANDE questionnaire assesses the frequency and severity of dry eye disease symptoms. Subjects used 2 unique, 100 mm Visual Analogue Scales (VAS) to mark the frequency of symptoms (0=rarely, 100=all the time) and the severity of symptoms (0=very mild, 100=very severe) for both eyes together. The Global SANDE score was calculated by multiplying the frequency score by the severity score and obtaining the square root. The final value was rounded nearest whole number. The SANDE questionnaire was completed at Baseline prior to CAE exposure and at Day 84 prior to CAE exposure. The Day 84 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 84 | Day 84 | The SANDE questionnaire assesses the frequency and severity of dry eye disease symptoms. Subjects used 2 unique, 100 mm Visual Analogue Scales (VAS) to mark the frequency of symptoms (0=rarely, 100=all the time) and the severity of symptoms (0=very mild, 100=very severe) for both eyes together. The Global SANDE score was calculated by multiplying the frequency score by the severity score and obtaining the square root. The final value was rounded nearest whole number. The SANDE questionnaire was completed prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 28 | Baseline (Day 1) (pre-treatment), Day 28 | Eye dryness was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no eye dryness) to 100 mm (maximum eye dryness). Eye dryness was assessed at Baseline prior to CAE exposure and at Day 28 prior to CAE exposure. The Day 28 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 28 | Day 28 | Ocular discomfort was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular discomfort) to 100 mm (maximum ocular discomfort) prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 84 | Baseline (Day 1) (pre-treatment), Day 84 | Eye dryness was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no eye dryness) to 100 mm (maximum eye dryness). Eye dryness was assessed at Baseline prior to CAE exposure and at Day 84 prior to CAE exposure. The Day 84 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 84 | Day 84 | Eye dryness was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no eye dryness) to 100 mm (maximum eye dryness) prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Change From Baseline in Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 14 | Baseline (Day 1) (pre-treatment), Day 14 | Ocular discomfort was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular discomfort) to 100 mm (maximum ocular discomfort). Ocular discomfort was assessed at Baseline prior to CAE exposure and at Day 14 prior to CAE exposure. The Day 14 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Mean Change From Baseline in Pre-CAE Ora Calibra® Ocular Discomfort Score (ODS) at Day 28 | Baseline (Day 1) (pre-treatment), Day 28 | Ocular discomfort was assessed using a 5-point proprietary scale where 0=no discomfort and 4=constant discomfort. Ocular discomfort was assessed at Baseline prior to CAE exposure and at Day 28 prior to CAE exposure. The Day 28 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. One eye (study eye) contributed data to the analysis. |
| Mean Change From Baseline in Pre-CAE Ora Calibra® Ocular Discomfort Score (ODS) at Day 84 | Baseline (Day 1) (pre-treatment), Day 84 | Ocular discomfort was assessed using a 5-point proprietary scale where 0=no discomfort and 4=constant discomfort. Ocular discomfort was assessed at Baseline prior to CAE exposure and at Day 84 prior to CAE exposure. The Day 84 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. One eye (study eye) contributed data to the analysis. |
| Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 14 | Day 14 | Ocular discomfort was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular discomfort) to 100 mm (maximum ocular discomfort) prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 14 | Baseline (Day 1) (pre-treatment), Day 14 | Ocular pain was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain). Ocular pain was assessed at Baseline prior to CAE exposure and at Day 14 prior to CAE exposure. The Day 14 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 14 | Day 14 | Ocular pain was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain) prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 14 | Baseline (Day 1) (pre-treatment), Day 14 | The SANDE questionnaire assesses the frequency and severity of dry eye disease symptoms. Subjects used 2 unique, 100 mm Visual Analogue Scales (VAS) to mark the frequency of symptoms (0=rarely, 100=all the time) and the severity of symptoms (0=very mild, 100=very severe) for both eyes together. The Global SANDE score was calculated by multiplying the frequency score by the severity score and obtaining the square root. The final value was rounded nearest whole number. The SANDE questionnaire was completed at Baseline prior to CAE exposure and at Day 14 prior to CAE exposure. The Day 14 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 14 | Day 14 | The SANDE questionnaire assesses the frequency and severity of dry eye disease symptoms. Subjects used 2 unique, 100 mm Visual Analogue Scales (VAS) to mark the frequency of symptoms (0=rarely, 100=all the time) and the severity of symptoms (0=very mild, 100=very severe) for both eyes together. The Global SANDE score was calculated by multiplying the frequency score by the severity score and obtaining the square root. The final value was rounded nearest whole number. The SANDE questionnaire was completed prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 14 | Baseline (Day 1) (pre-treatment), Day 14 | Eye dryness was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no eye dryness) to 100 mm (maximum eye dryness). Eye dryness was assessed at Baseline prior to CAE exposure and at Day 14 prior to CAE exposure. The Day 14 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 14 | Day 14 | Eye dryness was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no eye dryness) to 100 mm (maximum eye dryness) prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Percentage of Subjects With a Baseline Anesthetized Schirmer Score Equal to or Less That 5 mm That Achieved an Anesthetized Schirmer Score of Equal to or Greater Than 10 mm at Day 84 | Baseline (Day 1) (pre-treatment), Day 84 | The Schirmer test measures tear production. Following instillation of topical anesthetic drops, Schirmer strips were the placed on the lower eye lids, eyes were closed, and strips remained in place for 5 minutes or until both strips reached a maximum score. The strips were removed, and the amount of wetting was recorded on a scale from 0 mm (no tear production) to 35 mm (maximum tear production). The test was performed at Baseline prior to CAE exposure and at Day 84 prior to CAE exposure. A higher percentage indicates a better outcome. One eye (study eye) contributed data to the analysis. |
| Percentage of Subjects That Achieved at Least a 10 mm Increase in Pre-CAE Anesthetized Schirmer Score Relative to Baseline at Day 84 | Baseline (Day 1) (pre-treatment), Day 84 | The Schirmer test measures tear production. Following instillation of topical anesthetic drops, Schirmer strips were the placed on the lower eye lids, eyes were closed, and strips remained in place for 5 minutes or until both strips reached a maximum score. The strips were removed, and the amount of wetting was recorded on a scale from 0 mm (no tear production) to 35 mm (maximum tear production). The test was performed at Baseline prior to CAE exposure and at Day 84 prior to CAE exposure. A higher percentage indicates a better outcome. One eye (study eye) contributed data to the analysis. |
| Percentage of Subjects With a Baseline Anesthetized Schirmer Score Equal to or Less That 5 mm That Achieved an Anesthetized Schirmer Score of Equal to or Greater Than 10 mm at Day 28 | Baseline (Day 1) (pre-treatment), Day 28 | The Schirmer test measures tear production. Following instillation of topical anesthetic drops, Schirmer strips were the placed on the lower eye lids, eyes were closed, and strips remained in place for 5 minutes or until both strips reached a maximum score. The strips were removed, and the amount of wetting was recorded on a scale from 0 mm (no tear production) to 35 mm (maximum tear production). The test was performed at Baseline prior to CAE exposure and at Day 28 prior to CAE exposure. A higher percentage indicates a better outcome. One eye (study eye) contributed data to the analysis. |
| Percentage of Subjects That Achieved at Least a 10 mm Increase in Pre-CAE Anesthetized Schirmer Score Relative to Baseline at Day 28 | Baseline (Day 1) (pre-treatment), Day 28 | The Schirmer test measures tear production. Following instillation of topical anesthetic drops, Schirmer strips were the placed on the lower eye lids, eyes were closed, and strips remained in place for 5 minutes or until both strips reached a maximum score. The strips were removed, and the amount of wetting was recorded on a scale from 0 mm (no tear production) to 35 mm (maximum tear production). The test was performed at Baseline prior to CAE exposure and at Day 28 prior to CAE exposure. A higher percentage indicates a better outcome. One eye (study eye) contributed data to the analysis. |
| Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 28 | Day 28 | Eye dryness was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no eye dryness) to 100 mm (maximum eye dryness) prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Change From Baseline in Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 84 | Baseline (Day 1) (pre-treatment), Day 84 | Ocular discomfort was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular discomfort) to 100 mm (maximum ocular discomfort). Ocular discomfort was assessed at Baseline prior to CAE exposure and at Day 84 prior to CAE exposure. The Day 84 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from 15 clinical sites located in the United States.
Pre-assignment details
This reporting group includes all randomized participants.
Participants by arm
| Arm | Count |
|---|---|
| AR-15512 Ophthalmic Solution Higher Dose AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated. | 122 |
| AR-15512 Ophthalmic Solution Lower Dose AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated. | 121 |
| Vehicle AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated. | 126 |
| Total | 369 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 2 |
| Overall Study | Investigator Decision | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Non-Compliant | 1 | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 | 2 |
| Overall Study | Withdrawal of Consent | 3 | 4 | 3 |
Baseline characteristics
| Characteristic | AR-15512 Ophthalmic Solution Higher Dose | AR-15512 Ophthalmic Solution Lower Dose | Vehicle | Total |
|---|---|---|---|---|
| Age, Continuous | 62.6 years STANDARD_DEVIATION 13.01 | 65.5 years STANDARD_DEVIATION 10.89 | 63.1 years STANDARD_DEVIATION 11.9 | 63.7 years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 4 Participants | 10 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 116 Participants | 117 Participants | 116 Participants | 349 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian / Alaska Native | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Asian | 11 Participants | 8 Participants | 7 Participants | 26 Participants |
| Race/Ethnicity, Customized Black / African American | 18 Participants | 15 Participants | 18 Participants | 51 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 92 Participants | 97 Participants | 99 Participants | 288 Participants |
| Sex: Female, Male Female | 92 Participants | 82 Participants | 92 Participants | 266 Participants |
| Sex: Female, Male Male | 30 Participants | 39 Participants | 34 Participants | 103 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 369 | 0 / 122 | 0 / 122 | 0 / 121 | 0 / 121 | 0 / 126 | 0 / 126 |
| other Total, other adverse events | 11 / 369 | 53 / 122 | 0 / 122 | 45 / 121 | 0 / 121 | 4 / 126 | 0 / 126 |
| serious Total, serious adverse events | 0 / 369 | 0 / 122 | 1 / 122 | 0 / 121 | 1 / 121 | 0 / 126 | 2 / 126 |
Outcome results
Primary
Least Squares Mean Change From Baseline in Pre-CAE Anesthetized Schirmer Test Score at Day 28
The Schirmer test measures tear production. Following instillation of topical anesthetic drops, Schirmer strips were placed on the lower eye lids, eyes were closed, and strips remained in place for 5 minutes or until both strips reached a maximum score. The strips were removed, and the amount of wetting was recorded on a scale from 0 mm (no tear production) to 35 mm (maximum tear production). The test was performed at Baseline prior to CAE exposure and at Day 28 prior to CAE exposure. The Day 28 value was subtracted from the Baseline value. A more positive change value indicates a better outcome. One eye (study eye) contributed data to the analysis. This is a co-primary endpoint.
Time frame: Baseline (Day 1) (pre-treatment), Day 28
Population: ITT with data at both visits
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Change From Baseline in Pre-CAE Anesthetized Schirmer Test Score at Day 28 | 2.2 mm | Standard Error 0.53 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Change From Baseline in Pre-CAE Anesthetized Schirmer Test Score at Day 28 | 3.0 mm | Standard Error 0.53 |
| Vehicle | Least Squares Mean Change From Baseline in Pre-CAE Anesthetized Schirmer Test Score at Day 28 | 2.7 mm | Standard Error 0.53 |
p-value: 0.493695% CI: [-1.9, 0.9]ANCOVA
p-value: 0.713195% CI: [-1.1, 1.6]ANCOVA
Primary
Least Squares Mean Change From Baseline in Pre-CAE (Controlled Adverse Environment) Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 28
Ocular discomfort was assessed using a Visual Analogue Scale (VAS) that ranged from 0 millimeters (mm) (no ocular discomfort) to 100 mm (maximum ocular discomfort). Ocular discomfort was assessed at Baseline prior to CAE exposure and at Day 28 prior to CAE exposure. The Day 28 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. This is a co-primary endpoint.
Time frame: Baseline (Day 1) (pre-treatment), Day 28
Population: Intent-to-Treat (ITT) with data at both visits
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Change From Baseline in Pre-CAE (Controlled Adverse Environment) Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 28 | -15.3 millimeter (mm) | Standard Error 2.14 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Change From Baseline in Pre-CAE (Controlled Adverse Environment) Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 28 | -11.0 millimeter (mm) | Standard Error 2.12 |
| Vehicle | Least Squares Mean Change From Baseline in Pre-CAE (Controlled Adverse Environment) Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 28 | -11.9 millimeter (mm) | Standard Error 2.15 |
p-value: 0.230595% CI: [-8.9, 2.2]ANCOVA
p-value: 0.743695% CI: [-4.6, 6.4]ANCOVA
Secondary
Least Squares Mean Change From Baseline in Post-CAE Pain Score on a Visual Analogue Scale at Day 28
Ocular pain was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain). Ocular pain was assessed at Baseline prior to CAE exposure and at Day 28 following CAE exposure. The Day 28 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Baseline (Day 1) (pre-treatment), Day 28
Population: ITT with data at both visits
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Change From Baseline in Post-CAE Pain Score on a Visual Analogue Scale at Day 28 | -7.5 mm | Standard Error 2.64 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Change From Baseline in Post-CAE Pain Score on a Visual Analogue Scale at Day 28 | -7.2 mm | Standard Error 2.7 |
| Vehicle | Least Squares Mean Change From Baseline in Post-CAE Pain Score on a Visual Analogue Scale at Day 28 | -6.4 mm | Standard Error 2.71 |
p-value: 0.75695% CI: [-8.1, 5.9]ANCOVA
p-value: 0.830895% CI: [-7.9, 6.4]ANCOVA
Secondary
Least Squares Mean Change From Baseline in Post-CAE Pain Score on a Visual Analogue Scale at Day 84
Ocular pain was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain). Ocular pain was assessed at Baseline prior to CAE exposure and at Day 84 following CAE exposure. The Day 84 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Baseline (Day 1) (pre-treatment), Day 84
Population: ITT with data at both visits
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Change From Baseline in Post-CAE Pain Score on a Visual Analogue Scale at Day 84 | -17.6 mm | Standard Error 2.77 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Change From Baseline in Post-CAE Pain Score on a Visual Analogue Scale at Day 84 | -8.9 mm | Standard Error 2.85 |
| Vehicle | Least Squares Mean Change From Baseline in Post-CAE Pain Score on a Visual Analogue Scale at Day 84 | -12.1 mm | Standard Error 2.93 |
p-value: 0.151895% CI: [-13, 2]ANCOVA
p-value: 0.40795% CI: [-4.4, 10.8]ANCOVA
Secondary
Least Squares Mean Change From Baseline in Pre-CAE Anesthetized Schirmer Test Score at Day 84
The Schirmer test measures tear production. Following instillation of topical anesthetic drops, Schirmer strips were the placed on the lower eye lids, eyes were closed, and strips remained in place for 5 minutes or until both strips reached a maximum score. The strips were removed, and the amount of wetting was recorded on a scale from 0 mm (no tear production) to 35 mm (maximum tear production). The test was performed at Baseline prior to CAE exposure and at Day 84 prior to CAE exposure. The Day 84 value was subtracted from the Baseline value. A more positive change value indicates a better outcome. One eye (study eye) contributed data to the analysis.
Time frame: Baseline (Day 1) (pre-treatment), Day 84
Population: ITT with data at both visits
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Change From Baseline in Pre-CAE Anesthetized Schirmer Test Score at Day 84 | 2.9 mm | Standard Error 0.57 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Change From Baseline in Pre-CAE Anesthetized Schirmer Test Score at Day 84 | 3.2 mm | Standard Error 0.56 |
| Vehicle | Least Squares Mean Change From Baseline in Pre-CAE Anesthetized Schirmer Test Score at Day 84 | 2.9 mm | Standard Error 0.57 |
p-value: 0.984695% CI: [-1.5, 1.5]ANCOVA
p-value: 0.650895% CI: [-1.1, 1.8]ANCOVA
Secondary
Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 14
Eye dryness was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no eye dryness) to 100 mm (maximum eye dryness). Eye dryness was assessed at Baseline prior to CAE exposure and at Day 14 prior to CAE exposure. The Day 14 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Baseline (Day 1) (pre-treatment), Day 14
Population: ITT with data at both visits
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 14 | -8.8 mm | Standard Error 1.56 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 14 | -4.9 mm | Standard Error 1.56 |
| Vehicle | Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 14 | -4.9 mm | Standard Error 1.56 |
p-value: 0.057395% CI: [-8, 0.1]ANCOVA
p-value: 0.99395% CI: [-4, 4.1]ANCOVA
Secondary
Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 28
Eye dryness was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no eye dryness) to 100 mm (maximum eye dryness). Eye dryness was assessed at Baseline prior to CAE exposure and at Day 28 prior to CAE exposure. The Day 28 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Baseline (Day 1) (pre-treatment), Day 28
Population: ITT with data at both visits
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 28 | -11.3 mm | Standard Error 1.91 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 28 | -8.2 mm | Standard Error 1.9 |
| Vehicle | Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 28 | -7.8 mm | Standard Error 1.91 |
p-value: 0.15295% CI: [-8.5, 1.3]ANCOVA
p-value: 0.851595% CI: [-5.4, 4.4]ANCOVA
Secondary
Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 84
Eye dryness was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no eye dryness) to 100 mm (maximum eye dryness). Eye dryness was assessed at Baseline prior to CAE exposure and at Day 84 prior to CAE exposure. The Day 84 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Baseline (Day 1) (pre-treatment), Day 84
Population: ITT with data at both visits
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 84 | -17.1 mm | Standard Error 2.2 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 84 | -11.5 mm | Standard Error 2.21 |
| Vehicle | Least Squares Mean Change From Baseline in Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 84 | -10.8 mm | Standard Error 2.22 |
p-value: 0.030295% CI: [-12.1, -0.6]ANCOVA
p-value: 0.801395% CI: [-6.5, 5]ANCOVA
Secondary
Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 14
The SANDE questionnaire assesses the frequency and severity of dry eye disease symptoms. Subjects used 2 unique, 100 mm Visual Analogue Scales (VAS) to mark the frequency of symptoms (0=rarely, 100=all the time) and the severity of symptoms (0=very mild, 100=very severe) for both eyes together. The Global SANDE score was calculated by multiplying the frequency score by the severity score and obtaining the square root. The final value was rounded nearest whole number. The SANDE questionnaire was completed at Baseline prior to CAE exposure and at Day 14 prior to CAE exposure. The Day 14 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Baseline (Day 1) (pre-treatment), Day 14
Population: ITT with data at both visits
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 14 | -7.4 mm | Standard Error 1.5 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 14 | -5.9 mm | Standard Error 1.51 |
| Vehicle | Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 14 | -2.9 mm | Standard Error 1.5 |
p-value: 0.025495% CI: [-8.4, -0.6]ANCOVA
p-value: 0.136295% CI: [-6.9, 0.9]ANCOVA
Secondary
Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 28
The SANDE questionnaire assesses the frequency and severity of dry eye disease symptoms. Subjects used 2 unique, 100 mm Visual Analogue Scales (VAS) to mark the frequency of symptoms (0=rarely, 100=all the time) and the severity of symptoms (0=very mild, 100=very severe) for both eyes together. The Global SANDE score was calculated by multiplying the frequency score by the severity score and obtaining the square root. The final value was rounded nearest whole number. The SANDE questionnaire was completed at Baseline prior to CAE exposure and at Day 28 prior to CAE exposure. The Day 28 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Baseline (Day 1) (pre-treatment), Day 28
Population: ITT with data at both visits
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 28 | -12.9 mm | Standard Error 1.7 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 28 | -9.3 mm | Standard Error 1.69 |
| Vehicle | Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 28 | -5.0 mm | Standard Error 1.72 |
p-value: 0.000595% CI: [-12.4, -3.5]ANCOVA
p-value: 0.058595% CI: [-8.7, 0.2]ANCOVA
Secondary
Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 84
The SANDE questionnaire assesses the frequency and severity of dry eye disease symptoms. Subjects used 2 unique, 100 mm Visual Analogue Scales (VAS) to mark the frequency of symptoms (0=rarely, 100=all the time) and the severity of symptoms (0=very mild, 100=very severe) for both eyes together. The Global SANDE score was calculated by multiplying the frequency score by the severity score and obtaining the square root. The final value was rounded nearest whole number. The SANDE questionnaire was completed at Baseline prior to CAE exposure and at Day 84 prior to CAE exposure. The Day 84 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Baseline (Day 1) (pre-treatment), Day 84
Population: ITT with data at both visits
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 84 | -17.2 mm | Standard Error 2.09 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 84 | -9.5 mm | Standard Error 2.09 |
| Vehicle | Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 84 | -8.3 mm | Standard Error 2.12 |
p-value: 0.001595% CI: [-14.3, -3.4]ANCOVA
p-value: 0.681295% CI: [-6.6, 4.3]ANCOVA
Secondary
Least Squares Mean Change From Baseline in Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 14
Ocular discomfort was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular discomfort) to 100 mm (maximum ocular discomfort). Ocular discomfort was assessed at Baseline prior to CAE exposure and at Day 14 prior to CAE exposure. The Day 14 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Baseline (Day 1) (pre-treatment), Day 14
Population: ITT with data at both visits
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Change From Baseline in Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 14 | -10.1 mm | Standard Error 1.92 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Change From Baseline in Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 14 | -8.2 mm | Standard Error 1.92 |
| Vehicle | Least Squares Mean Change From Baseline in Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 14 | -10.7 mm | Standard Error 1.9 |
p-value: 0.816695% CI: [-4.4, 5.5]ANCOVA
p-value: 0.337195% CI: [-2.5, 7.4]ANCOVA
Secondary
Least Squares Mean Change From Baseline in Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 84
Ocular discomfort was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular discomfort) to 100 mm (maximum ocular discomfort). Ocular discomfort was assessed at Baseline prior to CAE exposure and at Day 84 prior to CAE exposure. The Day 84 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Baseline (Day 1) (pre-treatment), Day 84
Population: ITT with data at both visits
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Change From Baseline in Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 84 | -20.6 mm | Standard Error 2.4 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Change From Baseline in Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 84 | -13.3 mm | Standard Error 2.4 |
| Vehicle | Least Squares Mean Change From Baseline in Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 84 | -13.6 mm | Standard Error 2.42 |
p-value: 0.028195% CI: [-13.2, -0.8]ANCOVA
p-value: 0.918695% CI: [-5.9, 6.6]ANCOVA
Secondary
Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 14
Ocular pain was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain). Ocular pain was assessed at Baseline prior to CAE exposure and at Day 14 prior to CAE exposure. The Day 14 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Baseline (Day 1) (pre-treatment), Day 14
Population: ITT with data at both visits
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 14 | -4.3 mm | Standard Error 2.13 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 14 | -1.8 mm | Standard Error 2.14 |
| Vehicle | Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 14 | -6.1 mm | Standard Error 2.11 |
p-value: 0.521595% CI: [-3.7, 7.3]ANCOVA
p-value: 0.131295% CI: [-1.3, 9.8]ANCOVA
Secondary
Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 28
Ocular pain was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain). Ocular pain was assessed at Baseline prior to CAE exposure and at Day 28 prior to CAE exposure. The Day 28 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Baseline (Day 1) (pre-treatment), Day 28
Population: ITT with data at both visits
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 28 | -11.6 mm | Standard Error 2.39 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 28 | -6.6 mm | Standard Error 2.39 |
| Vehicle | Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 28 | -6.6 mm | Standard Error 2.41 |
p-value: 0.115395% CI: [-11.2, 1.2]ANCOVA
p-value: 0.997595% CI: [-6.2, 6.2]ANCOVA
Secondary
Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 84
Ocular pain was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain). Ocular pain was assessed at Baseline prior to CAE exposure and at Day 84 prior to CAE exposure. The Day 84 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Baseline (Day 1) (pre-treatment), Day 84
Population: ITT with data at both visits
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 84 | -18.3 mm | Standard Error 2.55 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 84 | -12.6 mm | Standard Error 2.57 |
| Vehicle | Least Squares Mean Change From Baseline in Pre-CAE Pain Score on a Visual Analogue Scale at Day 84 | -12.4 mm | Standard Error 2.58 |
p-value: 0.078695% CI: [-12.6, 0.7]ANCOVA
p-value: 0.947795% CI: [-6.9, 6.5]ANCOVA
Secondary
Least Squares Mean Post-CAE Pain Score on a Visual Analogue Scale at Day 28
Ocular pain was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain) following CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Day 28
Population: ITT with data at visit
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Post-CAE Pain Score on a Visual Analogue Scale at Day 28 | 59.7 mm | Standard Error 2.64 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Post-CAE Pain Score on a Visual Analogue Scale at Day 28 | 60.0 mm | Standard Error 2.7 |
| Vehicle | Least Squares Mean Post-CAE Pain Score on a Visual Analogue Scale at Day 28 | 60.8 mm | Standard Error 2.71 |
p-value: 0.75695% CI: [-8.1, 5.9]ANCOVA
p-value: 0.830895% CI: [-7.9, 6.4]ANCOVA
Secondary
Least Squares Mean Post-CAE Pain Score on a Visual Analogue Scale at Day 84
Ocular pain was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain) following CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Day 84
Population: ITT with data at visit
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Post-CAE Pain Score on a Visual Analogue Scale at Day 84 | 50.0 mm | Standard Error 2.77 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Post-CAE Pain Score on a Visual Analogue Scale at Day 84 | 58.7 mm | Standard Error 2.85 |
| Vehicle | Least Squares Mean Post-CAE Pain Score on a Visual Analogue Scale at Day 84 | 55.5 mm | Standard Error 2.93 |
p-value: 0.151895% CI: [-13, 2]ANCOVA
p-value: 0.40795% CI: [-4.4, 10.8]ANCOVA
Secondary
Least Squares Mean Pre-CAE Anesthetized Schirmer Test Score at Day 28
The Schirmer test measures tear production. Following instillation of topical anesthetic drops, Schirmer strips were the placed on the lower eye lids, eyes were closed, and strips remained in place for 5 minutes or until both strips reached a maximum score. The strips were removed, and the amount of wetting was recorded on a scale from 0 mm (no tear production) to 35 mm (maximum tear production). A higher score indicates a better outcome. The test was performed prior to CAE exposure. One eye (study eye) contributed data to the analysis.
Time frame: Day 28
Population: ITT with data at visit
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Pre-CAE Anesthetized Schirmer Test Score at Day 28 | 7.2 mm | Standard Error 0.53 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Pre-CAE Anesthetized Schirmer Test Score at Day 28 | 7.9 mm | Standard Error 0.53 |
| Vehicle | Least Squares Mean Pre-CAE Anesthetized Schirmer Test Score at Day 28 | 7.7 mm | Standard Error 0.53 |
p-value: 0.493695% CI: [-1.9, 0.9]ANCOVA
p-value: 0.713195% CI: [-1.1, 1.6]ANCOVA
Secondary
Least Squares Mean Pre-CAE Anesthetized Schirmer Test Score at Day 84
The Schirmer test measures tear production. Following instillation of topical anesthetic drops, Schirmer strips were the placed on the lower eye lids, eyes were closed, and strips remained in place for 5 minutes or until both strips reached a maximum score. The strips were removed, and the amount of wetting was recorded on a scale from 0 mm (no tear production) to 35 mm (maximum tear production). A higher score indicates a better outcome. The test was performed prior to CAE exposure. One eye (study eye) contributed data to the analysis.
Time frame: Day 84
Population: ITT with data at both visits
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Pre-CAE Anesthetized Schirmer Test Score at Day 84 | 7.9 mm | Standard Error 0.57 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Pre-CAE Anesthetized Schirmer Test Score at Day 84 | 8.2 mm | Standard Error 0.56 |
| Vehicle | Least Squares Mean Pre-CAE Anesthetized Schirmer Test Score at Day 84 | 7.9 mm | Standard Error 0.57 |
p-value: 0.984695% CI: [-1.5, 1.5]ANCOVA
p-value: 0.650895% CI: [-1.1, 1.8]ANCOVA
Secondary
Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 14
Eye dryness was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no eye dryness) to 100 mm (maximum eye dryness) prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Day 14
Population: ITT with data at visit
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 14 | 65.7 mm | Standard Error 1.56 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 14 | 69.7 mm | Standard Error 1.56 |
| Vehicle | Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 14 | 69.7 mm | Standard Error 1.56 |
p-value: 0.057395% CI: [-8, 0.1]ANCOVA
p-value: 0.99395% CI: [-4, 4.1]ANCOVA
Secondary
Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 28
Eye dryness was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no eye dryness) to 100 mm (maximum eye dryness) prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Day 28
Population: ITT with data at visit
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 28 | 63.4 mm | Standard Error 1.91 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 28 | 66.5 mm | Standard Error 1.9 |
| Vehicle | Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 28 | 66.9 mm | Standard Error 1.91 |
p-value: 0.15295% CI: [-8.5, 1.3]ANCOVA
p-value: 0.851595% CI: [-5.4, 4.4]ANCOVA
Secondary
Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 84
Eye dryness was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no eye dryness) to 100 mm (maximum eye dryness) prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Day 84
Population: ITT with data at visit
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 84 | 57.4 mm | Standard Error 2.2 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 84 | 63.0 mm | Standard Error 2.21 |
| Vehicle | Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 84 | 63.7 mm | Standard Error 2.22 |
p-value: 0.030295% CI: [-12.1, -0.6]ANCOVA
p-value: 0.801395% CI: [-6.5, 5]ANCOVA
Secondary
Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 14
The SANDE questionnaire assesses the frequency and severity of dry eye disease symptoms. Subjects used 2 unique, 100 mm Visual Analogue Scales (VAS) to mark the frequency of symptoms (0=rarely, 100=all the time) and the severity of symptoms (0=very mild, 100=very severe) for both eyes together. The Global SANDE score was calculated by multiplying the frequency score by the severity score and obtaining the square root. The final value was rounded nearest whole number. The SANDE questionnaire was completed prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Day 14
Population: ITT with data at visit
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 14 | 68.3 mm | Standard Error 1.5 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 14 | 69.8 mm | Standard Error 1.51 |
| Vehicle | Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 14 | 72.8 mm | Standard Error 1.5 |
p-value: 0.025495% CI: [-8.4, -0.6]ANCOVA
p-value: 0.136295% CI: [-6.9, 0.9]ANCOVA
Secondary
Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 28
The SANDE questionnaire assesses the frequency and severity of dry eye disease symptoms. Subjects used 2 unique, 100 mm Visual Analogue Scales (VAS) to mark the frequency of symptoms (0=rarely, 100=all the time) and the severity of symptoms (0=very mild, 100=very severe) for both eyes together. The Global SANDE score was calculated by multiplying the frequency score by the severity score and obtaining the square root. The final value was rounded nearest whole number. The SANDE questionnaire was completed prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Day 28
Population: ITT with data at visit
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 28 | 62.8 mm | Standard Error 1.7 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 28 | 66.5 mm | Standard Error 1.69 |
| Vehicle | Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 28 | 70.8 mm | Standard Error 1.72 |
p-value: 0.000595% CI: [-12.4, -3.5]ANCOVA
p-value: 0.058595% CI: [-8.7, 0.2]ANCOVA
Secondary
Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 84
The SANDE questionnaire assesses the frequency and severity of dry eye disease symptoms. Subjects used 2 unique, 100 mm Visual Analogue Scales (VAS) to mark the frequency of symptoms (0=rarely, 100=all the time) and the severity of symptoms (0=very mild, 100=very severe) for both eyes together. The Global SANDE score was calculated by multiplying the frequency score by the severity score and obtaining the square root. The final value was rounded nearest whole number. The SANDE questionnaire was completed prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Day 84
Population: ITT with data at visit
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 84 | 58.6 mm | Standard Error 2.09 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 84 | 66.3 mm | Standard Error 2.09 |
| Vehicle | Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 84 | 67.5 mm | Standard Error 2.12 |
p-value: 0.001595% CI: [-14.3, -3.4]ANCOVA
p-value: 0.681295% CI: [-6.6, 4.3]ANCOVA
Secondary
Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 14
Ocular discomfort was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular discomfort) to 100 mm (maximum ocular discomfort) prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Day 14
Population: ITT with data at visit
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 14 | 63.0 mm | Standard Error 1.92 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 14 | 64.8 mm | Standard Error 1.92 |
| Vehicle | Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 14 | 62.4 mm | Standard Error 1.9 |
p-value: 0.816695% CI: [-4.4, 5.5]ANCOVA
p-value: 0.337195% CI: [-2.5, 7.4]ANCOVA
Secondary
Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 28
Ocular discomfort was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular discomfort) to 100 mm (maximum ocular discomfort) prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Day 28
Population: ITT with data at visit
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 28 | 57.8 mm | Standard Error 2.14 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 28 | 62.1 mm | Standard Error 2.12 |
| Vehicle | Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 28 | 61.2 mm | Standard Error 2.15 |
p-value: 0.230595% CI: [-8.9, 2.2]ANCOVA
p-value: 0.743695% CI: [-4.6, 6.4]ANCOVA
Secondary
Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 84
Ocular discomfort was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular discomfort) to 100 mm (maximum ocular discomfort) prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Day 84
Population: ITT with data at visit
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 84 | 52.4 mm | Standard Error 2.4 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 84 | 59.7 mm | Standard Error 2.4 |
| Vehicle | Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 84 | 59.4 mm | Standard Error 2.42 |
p-value: 0.028195% CI: [-13.2, -0.8]ANCOVA
p-value: 0.918695% CI: [-5.9, 6.6]ANCOVA
Secondary
Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 14
Ocular pain was assessed using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain) prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Day 14
Population: ITT with data at visit
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 14 | 50.3 mm | Standard Error 2.13 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 14 | 52.8 mm | Standard Error 2.14 |
| Vehicle | Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 14 | 48.5 mm | Standard Error 2.11 |
p-value: 0.521595% CI: [-3.7, 7.3]ANCOVA
p-value: 0.131295% CI: [-1.3, 9.8]ANCOVA
Secondary
Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 28
Ocular pain was assessed prior to CAE exposure using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain) prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Day 28
Population: ITT with data at visit
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 28 | 43.0 mm | Standard Error 2.39 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 28 | 48.0 mm | Standard Error 2.39 |
| Vehicle | Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 28 | 48.0 mm | Standard Error 2.41 |
p-value: 0.115395% CI: [-11.2, 1.2]ANCOVA
p-value: 0.997595% CI: [-6.2, 6.2]ANCOVA
Secondary
Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 84
Ocular pain was assessed prior to CAE exposure using a Visual Analogue Scale (VAS) that ranged from 0 mm (no ocular pain) to 100 mm (maximum ocular pain) prior to CAE exposure. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Day 84
Population: ITT with data at visit
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 84 | 36.1 mm | Standard Error 2.55 |
| AR-15512 Ophthalmic Solution Lower Dose | Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 84 | 41.8 mm | Standard Error 2.57 |
| Vehicle | Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 84 | 42.1 mm | Standard Error 2.58 |
p-value: 0.078695% CI: [-12.6, 0.7]ANCOVA
p-value: 0.947795% CI: [-6.9, 6.5]ANCOVA
Secondary
Mean Change From Baseline in Pre-CAE Ora Calibra® Ocular Discomfort Score (ODS) at Day 28
Ocular discomfort was assessed using a 5-point proprietary scale where 0=no discomfort and 4=constant discomfort. Ocular discomfort was assessed at Baseline prior to CAE exposure and at Day 28 prior to CAE exposure. The Day 28 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. One eye (study eye) contributed data to the analysis.
Time frame: Baseline (Day 1) (pre-treatment), Day 28
Population: ITT with data at both visits
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Mean Change From Baseline in Pre-CAE Ora Calibra® Ocular Discomfort Score (ODS) at Day 28 | -0.4 score on a scale | Standard Deviation 1.03 |
| AR-15512 Ophthalmic Solution Lower Dose | Mean Change From Baseline in Pre-CAE Ora Calibra® Ocular Discomfort Score (ODS) at Day 28 | -0.4 score on a scale | Standard Deviation 1.02 |
| Vehicle | Mean Change From Baseline in Pre-CAE Ora Calibra® Ocular Discomfort Score (ODS) at Day 28 | -0.3 score on a scale | Standard Deviation 1.11 |
p-value: 0.3365Wilcoxon (Mann-Whitney)
p-value: 0.7323Wilcoxon (Mann-Whitney)
Secondary
Mean Change From Baseline in Pre-CAE Ora Calibra® Ocular Discomfort Score (ODS) at Day 84
Ocular discomfort was assessed using a 5-point proprietary scale where 0=no discomfort and 4=constant discomfort. Ocular discomfort was assessed at Baseline prior to CAE exposure and at Day 84 prior to CAE exposure. The Day 84 value was subtracted from the Baseline value. A more negative change value indicates a better outcome. One eye (study eye) contributed data to the analysis.
Time frame: Baseline (Day 1) (pre-treatment), Day 84
Population: ITT with data at both visits
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Mean Change From Baseline in Pre-CAE Ora Calibra® Ocular Discomfort Score (ODS) at Day 84 | -0.8 score on a scale | Standard Deviation 1.22 |
| AR-15512 Ophthalmic Solution Lower Dose | Mean Change From Baseline in Pre-CAE Ora Calibra® Ocular Discomfort Score (ODS) at Day 84 | -0.5 score on a scale | Standard Deviation 1.16 |
| Vehicle | Mean Change From Baseline in Pre-CAE Ora Calibra® Ocular Discomfort Score (ODS) at Day 84 | -0.5 score on a scale | Standard Deviation 1.34 |
p-value: 0.1557Wilcoxon (Mann-Whitney)
p-value: 0.6845Wilcoxon (Mann-Whitney)
Secondary
Percentage of Subjects That Achieved at Least a 10 mm Increase in Pre-CAE Anesthetized Schirmer Score Relative to Baseline at Day 28
The Schirmer test measures tear production. Following instillation of topical anesthetic drops, Schirmer strips were the placed on the lower eye lids, eyes were closed, and strips remained in place for 5 minutes or until both strips reached a maximum score. The strips were removed, and the amount of wetting was recorded on a scale from 0 mm (no tear production) to 35 mm (maximum tear production). The test was performed at Baseline prior to CAE exposure and at Day 28 prior to CAE exposure. A higher percentage indicates a better outcome. One eye (study eye) contributed data to the analysis.
Time frame: Baseline (Day 1) (pre-treatment), Day 28
Population: ITT with data at both visits
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Percentage of Subjects That Achieved at Least a 10 mm Increase in Pre-CAE Anesthetized Schirmer Score Relative to Baseline at Day 28 | 11.1 percentage of subjects |
| AR-15512 Ophthalmic Solution Lower Dose | Percentage of Subjects That Achieved at Least a 10 mm Increase in Pre-CAE Anesthetized Schirmer Score Relative to Baseline at Day 28 | 9.5 percentage of subjects |
| Vehicle | Percentage of Subjects That Achieved at Least a 10 mm Increase in Pre-CAE Anesthetized Schirmer Score Relative to Baseline at Day 28 | 7.6 percentage of subjects |
p-value: 0.437595% CI: [0.58, 3.58]Cochran-Mantel-Haenszel
p-value: 0.58495% CI: [0.51, 3.27]Cochran-Mantel-Haenszel
Secondary
Percentage of Subjects That Achieved at Least a 10 mm Increase in Pre-CAE Anesthetized Schirmer Score Relative to Baseline at Day 84
The Schirmer test measures tear production. Following instillation of topical anesthetic drops, Schirmer strips were the placed on the lower eye lids, eyes were closed, and strips remained in place for 5 minutes or until both strips reached a maximum score. The strips were removed, and the amount of wetting was recorded on a scale from 0 mm (no tear production) to 35 mm (maximum tear production). The test was performed at Baseline prior to CAE exposure and at Day 84 prior to CAE exposure. A higher percentage indicates a better outcome. One eye (study eye) contributed data to the analysis.
Time frame: Baseline (Day 1) (pre-treatment), Day 84
Population: ITT with data at both visits
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Percentage of Subjects That Achieved at Least a 10 mm Increase in Pre-CAE Anesthetized Schirmer Score Relative to Baseline at Day 84 | 7.8 percentage of subjects |
| AR-15512 Ophthalmic Solution Lower Dose | Percentage of Subjects That Achieved at Least a 10 mm Increase in Pre-CAE Anesthetized Schirmer Score Relative to Baseline at Day 84 | 13.2 percentage of subjects |
| Vehicle | Percentage of Subjects That Achieved at Least a 10 mm Increase in Pre-CAE Anesthetized Schirmer Score Relative to Baseline at Day 84 | 11.2 percentage of subjects |
p-value: 0.504695% CI: [0.29, 1.84]Cochran-Mantel-Haenszel
p-value: 0.575195% CI: [0.56, 2.88]Cochran-Mantel-Haenszel
Secondary
Percentage of Subjects With a Baseline Anesthetized Schirmer Score Equal to or Less That 5 mm That Achieved an Anesthetized Schirmer Score of Equal to or Greater Than 10 mm at Day 28
The Schirmer test measures tear production. Following instillation of topical anesthetic drops, Schirmer strips were the placed on the lower eye lids, eyes were closed, and strips remained in place for 5 minutes or until both strips reached a maximum score. The strips were removed, and the amount of wetting was recorded on a scale from 0 mm (no tear production) to 35 mm (maximum tear production). The test was performed at Baseline prior to CAE exposure and at Day 28 prior to CAE exposure. A higher percentage indicates a better outcome. One eye (study eye) contributed data to the analysis.
Time frame: Baseline (Day 1) (pre-treatment), Day 28
Population: ITT with data at both visit
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Percentage of Subjects With a Baseline Anesthetized Schirmer Score Equal to or Less That 5 mm That Achieved an Anesthetized Schirmer Score of Equal to or Greater Than 10 mm at Day 28 | 10.3 percentage of subjects |
| AR-15512 Ophthalmic Solution Lower Dose | Percentage of Subjects With a Baseline Anesthetized Schirmer Score Equal to or Less That 5 mm That Achieved an Anesthetized Schirmer Score of Equal to or Greater Than 10 mm at Day 28 | 9.5 percentage of subjects |
| Vehicle | Percentage of Subjects With a Baseline Anesthetized Schirmer Score Equal to or Less That 5 mm That Achieved an Anesthetized Schirmer Score of Equal to or Greater Than 10 mm at Day 28 | 13.6 percentage of subjects |
p-value: 0.286795% CI: [0.28, 1.46]Cochran-Mantel-Haenszel
p-value: 0.380395% CI: [0.32, 1.57]Cochran-Mantel-Haenszel
Secondary
Percentage of Subjects With a Baseline Anesthetized Schirmer Score Equal to or Less That 5 mm That Achieved an Anesthetized Schirmer Score of Equal to or Greater Than 10 mm at Day 84
The Schirmer test measures tear production. Following instillation of topical anesthetic drops, Schirmer strips were the placed on the lower eye lids, eyes were closed, and strips remained in place for 5 minutes or until both strips reached a maximum score. The strips were removed, and the amount of wetting was recorded on a scale from 0 mm (no tear production) to 35 mm (maximum tear production). The test was performed at Baseline prior to CAE exposure and at Day 84 prior to CAE exposure. A higher percentage indicates a better outcome. One eye (study eye) contributed data to the analysis.
Time frame: Baseline (Day 1) (pre-treatment), Day 84
Population: ITT with data at both visits
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| AR-15512 Ophthalmic Solution Higher Dose | Percentage of Subjects With a Baseline Anesthetized Schirmer Score Equal to or Less That 5 mm That Achieved an Anesthetized Schirmer Score of Equal to or Greater Than 10 mm at Day 84 | 16.5 percentage of subjects |
| AR-15512 Ophthalmic Solution Lower Dose | Percentage of Subjects With a Baseline Anesthetized Schirmer Score Equal to or Less That 5 mm That Achieved an Anesthetized Schirmer Score of Equal to or Greater Than 10 mm at Day 84 | 13.2 percentage of subjects |
| Vehicle | Percentage of Subjects With a Baseline Anesthetized Schirmer Score Equal to or Less That 5 mm That Achieved an Anesthetized Schirmer Score of Equal to or Greater Than 10 mm at Day 84 | 12.1 percentage of subjects |
p-value: 0.306895% CI: [0.7, 3.15]Cochran-Mantel-Haenszel
p-value: 0.616795% CI: [0.56, 2.68]Cochran-Mantel-Haenszel