Dry Eye Disease
Conditions
Brief summary
This will be a Phase 3, multicenter, vehicle-controlled, double-masked, randomized study conducted at approximately 20 sites in the United States. All subjects enrolled will have dry eye disease (DED). The study will consist of Screening (Day -14) and Baseline (Day 1) visits as well as visits at Day 7, Day 14, Day 28, and Day 90 (Study Exit) for an individual duration of participation of approximately 15 weeks.
Detailed description
At the end of the Screening Visit, all qualified subjects will be assigned to administer one drop of AR-15512 Vehicle twice a day to both eyes for approximately 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 enrolled in the study and randomized in a 1:1 ratio to receive 0.003% AR-15512 or AR-15512 Vehicle administered as 1 drop in each eye twice a day for 90 days. At the end of the Day 90 visit, subjects will exit the study. Aerie Pharmaceuticals was acquired by Alcon on November 22, 2022.
Interventions
Administered via topical ocular instillation
Inactive ingredients 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: * Signs and symptoms of dry eye disease (DED) at the Screening and Baseline visits; * Corrected visual acuity of +0.70 logarithm Minimum angle of resolution (LogMAR) or better in both eyes at 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; * Regular use of lid hygiene within 14 days prior to the Screening visit or any planned use during the study; * Use of artificial tears within 2 hours prior to the Screening visit or anticipated use during the study; * Medication use as specified in the protocol; * History or presence of significant systemic disease; * Other protocol-specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Who Achieved Equal to or Greater Than 10 Millimeter Increase From Pre-drop at Baseline to Post-drop on Day 14 in Study Eye Unanesthetized Schirmer Score | Baseline (Day 1) pre-drop; Day 14 post-drop | The Schirmer test measures tear production using a filter paper placed on the lower eyelid. The amount of wetting was recorded on a scale from 0 millimeters (mm) (no tear production) to 35 mm (maximum). The test was performed at Day 1 prior to drop exposure and at Day 14 following drop exposure. An increased score represents a positive outcome. One eye (study eye) contributed data to the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Least Squares Mean Change From Pre-drop Baseline in Unanesthetized Schirmer Score on Post-drop Day 14 (Study Eye) | Baseline (Day 1) pre-drop; Day 14 post-drop | The Schirmer test measures tear production using a filter paper placed on the lower eyelid. The amount of wetting was recorded on a scale from 0 millimeters (mm) (no tear production) to 35 mm (maximum). The test was performed at Day 1 prior to drop exposure and at Day 14 following drop exposure. The Day 14 value was compared to the Day 1 value. A positive change indicates a better outcome. One eye (study eye) contributed data to the analysis. |
| Percentage of Subjects Who Achieved Equal to or Greater Than 10 Millimeter Increase From Pre-drop at Baseline to Post-drop on Day 1 in Study Eye Unanesthetized Schirmer Score | Baseline (Day 1) pre-drop; Day 1 post-drop | The Schirmer test measures tear production using a filter paper placed on the lower eyelid. The amount of wetting was recorded on a scale from 0 millimeters (mm) (no tear production) to 35 mm (maximum). The test was performed at Day 1 prior to drop exposure and at Day 1 following drop exposure. The Day 1 post-drop score was compared to the Day 1 pre-drop score. An increased score represents a positive outcome. One eye (study eye) contributed data to the analysis. |
| Least Squares Mean Change From Pre-drop Baseline in Unanesthetized Schirmer Score on Post-drop Day 1 (Study Eye) | Baseline (Day 1) pre-drop; Day 1 post-drop | The Schirmer test measures tear production using a filter paper placed on the lower eyelid. The amount of wetting was recorded on a scale from 0 millimeters (mm) (no tear production) to 35 mm (maximum). The test was performed at Day 1 prior to drop exposure and at Day 1 following drop exposure. The Day 1 post-drop score was compared to the Day 1 pre-drop score. A positive change over time indicates a better outcome. One eye (study eye) contributed data to the analysis. |
| Percentage of Subjects Who Achieved Equal to or Greater Than 10 Millimeter Increase From Pre-drop at Baseline to Post-drop on Day 90 in Study Eye Unanesthetized Schirmer Score | Baseline (Day 1) pre-drop; Day 90 post-drop | The Schirmer test measures tear production using a filter paper placed on the lower eyelid. The amount of wetting was recorded on a scale from 0 millimeters (mm) (no tear production) to 35 mm (maximum). The test was performed at Day 1 prior to drop exposure and at Day 90 following drop exposure. The Day 90 post-drop score was compared to the Day 1 pre-drop score. An increased score represents a positive outcome. One eye (study eye) contributed data to the analysis. |
| Least Squares Mean Change From Pre-drop Baseline in Unanesthetized Schirmer Score on Post-drop Day 90 (Study Eye) | Baseline (Day 1) pre-drop; Day 90 post-drop | The Schirmer test measures tear production using a filter paper placed on the lower eyelid. The amount of wetting was recorded on a scale from 0 millimeters (mm) (no tear production) to 35 mm (maximum). The test was performed at Day 1 prior to drop exposure and at Day 90 following drop exposure. The Day 90 post-drop score was compared to the Day 1 pre-drop score. A positive change over time indicates a better outcome. One eye (study eye) contributed data to the analysis. |
| Least Squares Mean Change From Baseline in Global Symptom Assessment iN Dry Eye (SANDE) Score on Day 28 | Baseline (Day 1); Day 28 | The SANDE questionnaire assesses the frequency and severity of symptoms using 2 unique, 100 mm Visual Analog Scales to mark the frequency (0=rarely, 100=all the time) and severity (0=very mild, 100=very severe) of dry eye symptoms (prior to drop exposure). The 2 scores were multiplied and a square root was obtained for a resultant overall Global SANDE score of 0 to 100 where 0 represents no symptoms and 100 is maximum symptoms. A negative change indicates a better outcome. This was a subject based assessment (single score for both eyes). |
| Least Squares Mean Change From Baseline in SANDE Frequency Score on Day 90 | Baseline (Day 1); Day 90 | The SANDE questionnaire assesses the frequency of dry eye disease symptoms. Subjects used a 100 mm Visual Analog Scale (VAS) to mark the frequency of symptoms where 0=rarely and 100=all the time. A higher SANDE frequency score indicates greater symptoms of dryness and/or irritation. The questionnaire was completed at Day 1 and Day 90 prior to drop exposure (both visits). The Day 90 value was compared to the Day 1 value. A negative change indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Change From Baseline in SANDE Severity Score on Day 90 | Baseline (Day 1); Day 90 | The SANDE questionnaire assesses the severity of dry eye disease symptoms. Subjects used a 100 mm Visual Analog Scale (VAS) to mark the severity of symptoms where 0=very mild and 100=very severe. A higher SANDE severity score indicates greater symptoms of dryness and/or irritation. The questionnaire was completed at Day 1 and Day 90 prior to drop exposure (both visits). The Day 90 value was compared to the Day 1 value. A negative change indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Change From Baseline in Eye Dryness Score (EDS) on Day 90 | Baseline (Day 1); Day 90 | The subject used a 100 mm Visual Analog Scale (VAS) to mark their eye dryness, where 0=no eye dryness and 100=maximum eye dryness. Eye dryness was assessed at Day 1 and Day 90 prior to drop exposure (both visits). A higher eye dryness score indicates greater dryness. The Day 90 value was compared to the Day 1 value. A negative change indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Change From Baseline in Ocular Discomfort Score (ODS) on Day 90 | Baseline (Day 1); Day 90 | The subject used a 100 mm Visual Analog Scale (VAS) to mark their eye dryness, where 0=no ocular discomfort and 100 mm=maximum ocular discomfort. A higher ocular discomfort score indicates greater discomfort. Ocular discomfort was assessed at Day 1 and Day 90 prior to drop exposure (both visits). The Day 90 value was compared to the Day 1 value. A negative change indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes. |
| Least Squares Mean Change From Baseline in Global SANDE Score on Day 90 | Baseline (Day 1); Day 90 | The SANDE questionnaire assesses the frequency and severity of symptoms using 2 unique, 100 mm Visual Analog Scales to mark the frequency (0=rarely, 100=all the time) and severity (0=very mild, 100=very severe) of dry eye symptoms (prior to drop exposure). The 2 scores were multiplied and a square root was obtained for a resultant overall Global SANDE score of 0 to 100 where 0 represents no symptoms and 100 is maximum symptoms. A negative change indicates a better outcome. This was a subject based assessment (single score for both eyes). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from 23 investigative sites located in the United States.
Pre-assignment details
This reporting group includes all randomized participants.
Participants by arm
| Arm | Count |
|---|---|
| 0.003% AR-15512 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 90 days | 230 |
| AR-15512 Vehicle AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 90 days | 235 |
| Total | 465 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 |
| Overall Study | As specified in the Clinical Study Report | 7 | 3 |
| Overall Study | Disallowed Concurrent Medication | 1 | 1 |
| Overall Study | Investigator Decision | 2 | 0 |
| Overall Study | Lost to Follow-up | 4 | 6 |
| Overall Study | Noncompliance | 0 | 4 |
| Overall Study | Protocol Deviation | 1 | 0 |
| Overall Study | Withdrawal of Consent | 2 | 5 |
Baseline characteristics
| Characteristic | Total | AR-15512 Vehicle | 0.003% AR-15512 |
|---|---|---|---|
| Age, Continuous | 59.6 years STANDARD_DEVIATION 13.23 | 59.6 years STANDARD_DEVIATION 13.43 | 59.5 years STANDARD_DEVIATION 13.04 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 65 Participants | 34 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 400 Participants | 201 Participants | 199 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Eye Dryness Score at Baseline (Day 1) | 72.2 millimeter STANDARD_DEVIATION 14.16 | 71.5 millimeter STANDARD_DEVIATION 13.54 | 72.8 millimeter STANDARD_DEVIATION 14.77 |
| Global SANDE Score at Baseline (Day 1) | 72.7 millimeter STANDARD_DEVIATION 11.94 | 72.7 millimeter STANDARD_DEVIATION 11.74 | 72.7 millimeter STANDARD_DEVIATION 12.16 |
| Ocular Discomfort Score at Baseline (Day 1) | 73.9 millimeter STANDARD_DEVIATION 12.39 | 73.4 millimeter STANDARD_DEVIATION 12.11 | 74.4 millimeter STANDARD_DEVIATION 12.67 |
| Race/Ethnicity, Customized American Indian / Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 45 Participants | 21 Participants | 24 Participants |
| Race/Ethnicity, Customized Black / African American | 67 Participants | 32 Participants | 35 Participants |
| Race/Ethnicity, Customized Multi-racial | 3 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 347 Participants | 179 Participants | 168 Participants |
| Region of Enrollment United States | 465 participants | 235 participants | 230 participants |
| SANDE Frequency Score at Baseline (Day 1) | 75.1 millimeter STANDARD_DEVIATION 13.74 | 75.0 millimeter STANDARD_DEVIATION 13.74 | 75.2 millimeter STANDARD_DEVIATION 13.77 |
| SANDE Severity Score at Baseline (Day 1) | 71.2 millimeter STANDARD_DEVIATION 12.95 | 71.3 millimeter STANDARD_DEVIATION 12.64 | 71.1 millimeter STANDARD_DEVIATION 13.28 |
| Sex: Female, Male Female | 353 Participants | 180 Participants | 173 Participants |
| Sex: Female, Male Male | 112 Participants | 55 Participants | 57 Participants |
| Unanesthetized Schirmer Test Pre-Drop at Baseline (Day 1) | 6.1 milllimeter STANDARD_DEVIATION 5.45 | 5.9 milllimeter STANDARD_DEVIATION 5.41 | 6.2 milllimeter STANDARD_DEVIATION 5.49 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 465 | 0 / 0 | 0 / 230 | 0 / 0 | 0 / 235 |
| other Total, other adverse events | 4 / 465 | 120 / 230 | 0 / 230 | 10 / 235 | 0 / 235 |
| serious Total, serious adverse events | 1 / 465 | 0 / 230 | 1 / 230 | 0 / 235 | 6 / 235 |
Outcome results
Primary
Percentage of Subjects Who Achieved Equal to or Greater Than 10 Millimeter Increase From Pre-drop at Baseline to Post-drop on Day 14 in Study Eye Unanesthetized Schirmer Score
The Schirmer test measures tear production using a filter paper placed on the lower eyelid. The amount of wetting was recorded on a scale from 0 millimeters (mm) (no tear production) to 35 mm (maximum). The test was performed at Day 1 prior to drop exposure and at Day 14 following drop exposure. An increased score represents a positive outcome. One eye (study eye) contributed data to the analysis.
Time frame: Baseline (Day 1) pre-drop; Day 14 post-drop
Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.003% AR-15512 | Percentage of Subjects Who Achieved Equal to or Greater Than 10 Millimeter Increase From Pre-drop at Baseline to Post-drop on Day 14 in Study Eye Unanesthetized Schirmer Score | 42.6 percentage of subjects |
| AR-15512 Vehicle | Percentage of Subjects Who Achieved Equal to or Greater Than 10 Millimeter Increase From Pre-drop at Baseline to Post-drop on Day 14 in Study Eye Unanesthetized Schirmer Score | 8.2 percentage of subjects |
Comparison: The primary estimand targeted the treatment effect attributable to the randomly assigned treatment, regardless of compliance to study treatment and assuming subjects who discontinued due to lack of efficacy, AEs, or disallowed concurrent treatments followed the behavior of subjects in the reference arm for the duration of the study and subjects who discontinued for other reasons would have followed the behavior of subjects who were still in the study under same randomly assigned treatment.p-value: <0.000195% CI: [26.9, 42]Pearson's Chi-squared test
Secondary
Least Squares Mean Change From Baseline in Eye Dryness Score (EDS) on Day 90
The subject used a 100 mm Visual Analog Scale (VAS) to mark their eye dryness, where 0=no eye dryness and 100=maximum eye dryness. Eye dryness was assessed at Day 1 and Day 90 prior to drop exposure (both visits). A higher eye dryness score indicates greater dryness. The Day 90 value was compared to the Day 1 value. A negative change indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Baseline (Day 1); Day 90
Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.003% AR-15512 | Least Squares Mean Change From Baseline in Eye Dryness Score (EDS) on Day 90 | -22.5 millimeter | Standard Error 1.89 |
| AR-15512 Vehicle | Least Squares Mean Change From Baseline in Eye Dryness Score (EDS) on Day 90 | -19.1 millimeter | Standard Error 1.84 |
Comparison: The primary estimand targeted the treatment effect attributable to the randomly assigned treatment, regardless of compliance to study treatment and assuming subjects who discontinued due to lack of efficacy, AEs, or disallowed concurrent treatments followed the behavior of subjects in the reference arm for the duration of the study and subjects who discontinued for other reasons would have followed the behavior of subjects who were still in the study under same randomly assigned treatment.p-value: 0.15995% CI: [-8.2, 1.3]ANCOVA
Secondary
Least Squares Mean Change From Baseline in Global SANDE Score on Day 90
The SANDE questionnaire assesses the frequency and severity of symptoms using 2 unique, 100 mm Visual Analog Scales to mark the frequency (0=rarely, 100=all the time) and severity (0=very mild, 100=very severe) of dry eye symptoms (prior to drop exposure). The 2 scores were multiplied and a square root was obtained for a resultant overall Global SANDE score of 0 to 100 where 0 represents no symptoms and 100 is maximum symptoms. A negative change indicates a better outcome. This was a subject based assessment (single score for both eyes).
Time frame: Baseline (Day 1); Day 90
Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.003% AR-15512 | Least Squares Mean Change From Baseline in Global SANDE Score on Day 90 | -23.5 millimeter | Standard Error 1.78 |
| AR-15512 Vehicle | Least Squares Mean Change From Baseline in Global SANDE Score on Day 90 | -20.7 millimeter | Standard Error 1.77 |
Comparison: The primary estimand targeted the treatment effect attributable to the randomly assigned treatment, regardless of compliance to study treatment and assuming subjects who discontinued due to lack of efficacy, AEs, or disallowed concurrent treatments followed the behavior of subjects in the reference arm for the duration of the study and subjects who discontinued for other reasons would have followed the behavior of subjects who were still in the study under same randomly assigned treatment.p-value: 0.218495% CI: [-7.3, 1.7]ANCOVA
Secondary
Least Squares Mean Change From Baseline in Global Symptom Assessment iN Dry Eye (SANDE) Score on Day 28
The SANDE questionnaire assesses the frequency and severity of symptoms using 2 unique, 100 mm Visual Analog Scales to mark the frequency (0=rarely, 100=all the time) and severity (0=very mild, 100=very severe) of dry eye symptoms (prior to drop exposure). The 2 scores were multiplied and a square root was obtained for a resultant overall Global SANDE score of 0 to 100 where 0 represents no symptoms and 100 is maximum symptoms. A negative change indicates a better outcome. This was a subject based assessment (single score for both eyes).
Time frame: Baseline (Day 1); Day 28
Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.003% AR-15512 | Least Squares Mean Change From Baseline in Global Symptom Assessment iN Dry Eye (SANDE) Score on Day 28 | -19.7 millimeter | Standard Error 1.61 |
| AR-15512 Vehicle | Least Squares Mean Change From Baseline in Global Symptom Assessment iN Dry Eye (SANDE) Score on Day 28 | -14.7 millimeter | Standard Error 1.58 |
Comparison: The primary estimand targeted the treatment effect attributable to the randomly assigned treatment, regardless of compliance to study treatment and assuming subjects who discontinued due to lack of efficacy, AEs, or disallowed concurrent treatments followed the behavior of subjects in the reference arm for the duration of the study and subjects who discontinued for other reasons would have followed the behavior of subjects who were still in the study under same randomly assigned treatment.p-value: 0.013895% CI: [-9.1, -1]ANCOVA
Secondary
Least Squares Mean Change From Baseline in Ocular Discomfort Score (ODS) on Day 90
The subject used a 100 mm Visual Analog Scale (VAS) to mark their eye dryness, where 0=no ocular discomfort and 100 mm=maximum ocular discomfort. A higher ocular discomfort score indicates greater discomfort. Ocular discomfort was assessed at Day 1 and Day 90 prior to drop exposure (both visits). The Day 90 value was compared to the Day 1 value. A negative change indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Baseline (Day 1); Day 90
Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.003% AR-15512 | Least Squares Mean Change From Baseline in Ocular Discomfort Score (ODS) on Day 90 | -32.2 millimeter | Standard Error 2.06 |
| AR-15512 Vehicle | Least Squares Mean Change From Baseline in Ocular Discomfort Score (ODS) on Day 90 | -28.2 millimeter | Standard Error 2.04 |
Comparison: The primary estimand targeted the treatment effect attributable to the randomly assigned treatment, regardless of compliance to study treatment and assuming subjects who discontinued due to lack of efficacy, AEs, or disallowed concurrent treatments followed the behavior of subjects in the reference arm for the duration of the study and subjects who discontinued for other reasons would have followed the behavior of subjects who were still in the study under same randomly assigned treatment.p-value: 0.136995% CI: [-9.2, 1.3]ANCOVA
Secondary
Least Squares Mean Change From Baseline in SANDE Frequency Score on Day 90
The SANDE questionnaire assesses the frequency of dry eye disease symptoms. Subjects used a 100 mm Visual Analog Scale (VAS) to mark the frequency of symptoms where 0=rarely and 100=all the time. A higher SANDE frequency score indicates greater symptoms of dryness and/or irritation. The questionnaire was completed at Day 1 and Day 90 prior to drop exposure (both visits). The Day 90 value was compared to the Day 1 value. A negative change indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Baseline (Day 1); Day 90
Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.003% AR-15512 | Least Squares Mean Change From Baseline in SANDE Frequency Score on Day 90 | -22.8 millimeter | Standard Error 1.89 |
| AR-15512 Vehicle | Least Squares Mean Change From Baseline in SANDE Frequency Score on Day 90 | -20.1 millimeter | Standard Error 1.89 |
Comparison: The primary estimand targeted the treatment effect attributable to the randomly assigned treatment, regardless of compliance to study treatment and assuming subjects who discontinued due to lack of efficacy, AEs, or disallowed concurrent treatments followed the behavior of subjects in the reference arm for the duration of the study and subjects who discontinued for other reasons would have followed the behavior of subjects who were still in the study under same randomly assigned treatment.p-value: 0.26694% CI: [-7.5, 2.1]ANCOVA
Secondary
Least Squares Mean Change From Baseline in SANDE Severity Score on Day 90
The SANDE questionnaire assesses the severity of dry eye disease symptoms. Subjects used a 100 mm Visual Analog Scale (VAS) to mark the severity of symptoms where 0=very mild and 100=very severe. A higher SANDE severity score indicates greater symptoms of dryness and/or irritation. The questionnaire was completed at Day 1 and Day 90 prior to drop exposure (both visits). The Day 90 value was compared to the Day 1 value. A negative change indicates a better outcome. This was a subject based assessment, and subject assigned a single score for both eyes.
Time frame: Baseline (Day 1); Day 90
Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.003% AR-15512 | Least Squares Mean Change From Baseline in SANDE Severity Score on Day 90 | -23.1 millimeter | Standard Error 1.87 |
| AR-15512 Vehicle | Least Squares Mean Change From Baseline in SANDE Severity Score on Day 90 | -20.5 millimeter | Standard Error 1.84 |
Comparison: The primary estimand targeted the treatment effect attributable to the randomly assigned treatment, regardless of compliance to study treatment and assuming subjects who discontinued due to lack of efficacy, AEs, or disallowed concurrent treatments followed the behavior of subjects in the reference arm for the duration of the study and subjects who discontinued for other reasons would have followed the behavior of subjects who were still in the study under same randomly assigned treatment.p-value: 0.274195% CI: [-7.2, 2]ANCOVA
Secondary
Least Squares Mean Change From Pre-drop Baseline in Unanesthetized Schirmer Score on Post-drop Day 14 (Study Eye)
The Schirmer test measures tear production using a filter paper placed on the lower eyelid. The amount of wetting was recorded on a scale from 0 millimeters (mm) (no tear production) to 35 mm (maximum). The test was performed at Day 1 prior to drop exposure and at Day 14 following drop exposure. The Day 14 value was compared to the Day 1 value. A positive change indicates a better outcome. One eye (study eye) contributed data to the analysis.
Time frame: Baseline (Day 1) pre-drop; Day 14 post-drop
Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.003% AR-15512 | Least Squares Mean Change From Pre-drop Baseline in Unanesthetized Schirmer Score on Post-drop Day 14 (Study Eye) | 9.8 millimeter | Standard Error 0.55 |
| AR-15512 Vehicle | Least Squares Mean Change From Pre-drop Baseline in Unanesthetized Schirmer Score on Post-drop Day 14 (Study Eye) | 2.6 millimeter | Standard Error 0.54 |
Comparison: The primary estimand targeted the treatment effect attributable to the randomly assigned treatment, regardless of compliance to study treatment and assuming subjects who discontinued due to lack of efficacy, AEs, or disallowed concurrent treatments followed the behavior of subjects in the reference arm for the duration of the study and subjects who discontinued for other reasons would have followed the behavior of subjects who were still in the study under same randomly assigned treatment.p-value: <0.000195% CI: [5.8, 8.6]ANCOVA
Secondary
Least Squares Mean Change From Pre-drop Baseline in Unanesthetized Schirmer Score on Post-drop Day 1 (Study Eye)
The Schirmer test measures tear production using a filter paper placed on the lower eyelid. The amount of wetting was recorded on a scale from 0 millimeters (mm) (no tear production) to 35 mm (maximum). The test was performed at Day 1 prior to drop exposure and at Day 1 following drop exposure. The Day 1 post-drop score was compared to the Day 1 pre-drop score. A positive change over time indicates a better outcome. One eye (study eye) contributed data to the analysis.
Time frame: Baseline (Day 1) pre-drop; Day 1 post-drop
Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.003% AR-15512 | Least Squares Mean Change From Pre-drop Baseline in Unanesthetized Schirmer Score on Post-drop Day 1 (Study Eye) | 8.9 millimeter | Standard Deviation 0.53 |
| AR-15512 Vehicle | Least Squares Mean Change From Pre-drop Baseline in Unanesthetized Schirmer Score on Post-drop Day 1 (Study Eye) | 2.7 millimeter | Standard Deviation 0.52 |
Comparison: The primary estimand targeted the treatment effect attributable to the randomly assigned treatment, regardless of compliance to study treatment and assuming subjects who discontinued due to lack of efficacy, AEs, or disallowed concurrent treatments followed the behavior of subjects in the reference arm for the duration of the study and subjects who discontinued for other reasons would have followed the behavior of subjects who were still in the study under same randomly assigned treatment.p-value: <0.000195% CI: [4.9, 7.5]ANCOVA
Secondary
Least Squares Mean Change From Pre-drop Baseline in Unanesthetized Schirmer Score on Post-drop Day 90 (Study Eye)
The Schirmer test measures tear production using a filter paper placed on the lower eyelid. The amount of wetting was recorded on a scale from 0 millimeters (mm) (no tear production) to 35 mm (maximum). The test was performed at Day 1 prior to drop exposure and at Day 90 following drop exposure. The Day 90 post-drop score was compared to the Day 1 pre-drop score. A positive change over time indicates a better outcome. One eye (study eye) contributed data to the analysis.
Time frame: Baseline (Day 1) pre-drop; Day 90 post-drop
Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 0.003% AR-15512 | Least Squares Mean Change From Pre-drop Baseline in Unanesthetized Schirmer Score on Post-drop Day 90 (Study Eye) | 10.7 millimeter | Standard Error 0.59 |
| AR-15512 Vehicle | Least Squares Mean Change From Pre-drop Baseline in Unanesthetized Schirmer Score on Post-drop Day 90 (Study Eye) | 3.1 millimeter | Standard Error 0.57 |
Comparison: The primary estimand targeted the treatment effect attributable to the randomly assigned treatment, regardless of compliance to study treatment and assuming subjects who discontinued due to lack of efficacy, AEs, or disallowed concurrent treatments followed the behavior of subjects in the reference arm for the duration of the study and subjects who discontinued for other reasons would have followed the behavior of subjects who were still in the study under same randomly assigned treatment.p-value: <0.000195% CI: [6, 9]ANCOVA
Secondary
Percentage of Subjects Who Achieved Equal to or Greater Than 10 Millimeter Increase From Pre-drop at Baseline to Post-drop on Day 1 in Study Eye Unanesthetized Schirmer Score
The Schirmer test measures tear production using a filter paper placed on the lower eyelid. The amount of wetting was recorded on a scale from 0 millimeters (mm) (no tear production) to 35 mm (maximum). The test was performed at Day 1 prior to drop exposure and at Day 1 following drop exposure. The Day 1 post-drop score was compared to the Day 1 pre-drop score. An increased score represents a positive outcome. One eye (study eye) contributed data to the analysis.
Time frame: Baseline (Day 1) pre-drop; Day 1 post-drop
Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.003% AR-15512 | Percentage of Subjects Who Achieved Equal to or Greater Than 10 Millimeter Increase From Pre-drop at Baseline to Post-drop on Day 1 in Study Eye Unanesthetized Schirmer Score | 36.1 percentage of subjects |
| AR-15512 Vehicle | Percentage of Subjects Who Achieved Equal to or Greater Than 10 Millimeter Increase From Pre-drop at Baseline to Post-drop on Day 1 in Study Eye Unanesthetized Schirmer Score | 9.4 percentage of subjects |
Comparison: The primary estimand targeted the treatment effect attributable to the randomly assigned treatment, regardless of compliance to study treatment and assuming subjects who discontinued due to lack of efficacy, AEs, or disallowed concurrent treatments followed the behavior of subjects in the reference arm for the duration of the study and subjects who discontinued for other reasons would have followed the behavior of subjects who were still in the study under same randomly assigned treatment.p-value: <0.000195% CI: [19.5, 34]Pearson's Chi-squared test
Secondary
Percentage of Subjects Who Achieved Equal to or Greater Than 10 Millimeter Increase From Pre-drop at Baseline to Post-drop on Day 90 in Study Eye Unanesthetized Schirmer Score
The Schirmer test measures tear production using a filter paper placed on the lower eyelid. The amount of wetting was recorded on a scale from 0 millimeters (mm) (no tear production) to 35 mm (maximum). The test was performed at Day 1 prior to drop exposure and at Day 90 following drop exposure. The Day 90 post-drop score was compared to the Day 1 pre-drop score. An increased score represents a positive outcome. One eye (study eye) contributed data to the analysis.
Time frame: Baseline (Day 1) pre-drop; Day 90 post-drop
Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 0.003% AR-15512 | Percentage of Subjects Who Achieved Equal to or Greater Than 10 Millimeter Increase From Pre-drop at Baseline to Post-drop on Day 90 in Study Eye Unanesthetized Schirmer Score | 46.7 percentage of subjects |
| AR-15512 Vehicle | Percentage of Subjects Who Achieved Equal to or Greater Than 10 Millimeter Increase From Pre-drop at Baseline to Post-drop on Day 90 in Study Eye Unanesthetized Schirmer Score | 13.6 percentage of subjects |
Comparison: The primary estimand targeted the treatment effect attributable to the randomly assigned treatment, regardless of compliance to study treatment and assuming subjects who discontinued due to lack of efficacy, AEs, or disallowed concurrent treatments followed the behavior of subjects in the reference arm for the duration of the study and subjects who discontinued for other reasons would have followed the behavior of subjects who were still in the study under same randomly assigned treatment.p-value: <0.000195% CI: [24.8, 41.4]Pearson's Chi-squared test