Trial Outcomes & Findings for A Phase 2b Study Evaluating the Safety and Efficacy of AR-15512 Ophthalmic Solution for the Treatment of Dry Eye Disease (NCT NCT04498182)

NCT ID: NCT04498182

Last Updated: 2024-08-28

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 369 participants
• Primary outcome timeframe: Baseline (Day 1) (pre-treatment), Day 28
• Results posted on: 2024-08-28

Participant Flow

Participants were recruited from 15 clinical sites located in the United States.

This reporting group includes all randomized participants.

Unit of analysis: eyes

Participant milestones

Measure	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.	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.	Vehicle AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Overall Study STARTED	122 244	121 242	126 252
Overall Study COMPLETED	115 230	114 228	116 232
Overall Study NOT COMPLETED	7 14	7 14	10 20

Reasons for withdrawal

Measure	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.	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.	Vehicle AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Overall Study Adverse Event	2	3	2
Overall Study Withdrawal of Consent	3	4	3
Overall Study Non-Compliant	1	0	1
Overall Study Lost to Follow-up	0	0	1
Overall Study Investigator Decision	0	0	1
Overall Study Protocol Violation	1	0	2

Baseline Characteristics

A Phase 2b Study Evaluating the Safety and Efficacy of AR-15512 Ophthalmic Solution for the Treatment of Dry Eye Disease

Baseline characteristics by cohort

Measure	AR-15512 Ophthalmic Solution Higher Dose n=122 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=121 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=126 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.	Total n=369 Participants Total of all reporting groups
Age, Continuous	62.6 years STANDARD_DEVIATION 13.01 • n=5 Participants	65.5 years STANDARD_DEVIATION 10.89 • n=7 Participants	63.1 years STANDARD_DEVIATION 11.90 • n=5 Participants	63.7 years STANDARD_DEVIATION 12.00 • n=4 Participants
Sex: Female, Male Female	92 Participants n=5 Participants	82 Participants n=7 Participants	92 Participants n=5 Participants	266 Participants n=4 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	39 Participants n=7 Participants	34 Participants n=5 Participants	103 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants	20 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	116 Participants n=5 Participants	117 Participants n=7 Participants	116 Participants n=5 Participants	349 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized American Indian / Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Asian	11 Participants n=5 Participants	8 Participants n=7 Participants	7 Participants n=5 Participants	26 Participants n=4 Participants
Race/Ethnicity, Customized Black / African American	18 Participants n=5 Participants	15 Participants n=7 Participants	18 Participants n=5 Participants	51 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized White	92 Participants n=5 Participants	97 Participants n=7 Participants	99 Participants n=5 Participants	288 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 28

Population: Intent-to-Treat (ITT) with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=118 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=119 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=119 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
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	-11.0 millimeter (mm) Standard Error 2.12	-11.9 millimeter (mm) Standard Error 2.15

PRIMARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 28

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=117 eyes AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=116 eyes AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=118 eyes AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Change From Baseline in Pre-CAE Anesthetized Schirmer Test Score at Day 28	2.2 mm Standard Error 0.53	3.0 mm Standard Error 0.53	2.7 mm Standard Error 0.53

SECONDARY outcome

Timeframe: Day 28

Population: ITT with data at visit

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=118 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=119 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=119 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 28	57.8 mm Standard Error 2.14	62.1 mm Standard Error 2.12	61.2 mm Standard Error 2.15

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 84

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=115 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=114 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=116 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
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 2.40	-13.3 mm Standard Error 2.40	-13.6 mm Standard Error 2.42

SECONDARY outcome

Timeframe: Day 84

Population: ITT with data at visit

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=115 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=114 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=116 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 84	52.4 mm Standard Error 2.40	59.7 mm Standard Error 2.40	59.4 mm Standard Error 2.42

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 84

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=115 eyes AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=114 eyes AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=116 eyes AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Change From Baseline in Pre-CAE Anesthetized Schirmer Test Score at Day 84	2.9 mm Standard Error 0.57	3.2 mm Standard Error 0.56	2.9 mm Standard Error 0.57

SECONDARY outcome

Timeframe: Day 84

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=115 eyes AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=114 eyes AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=116 eyes AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Pre-CAE Anesthetized Schirmer Test Score at Day 84	7.9 mm Standard Error 0.57	8.2 mm Standard Error 0.56	7.9 mm Standard Error 0.57

SECONDARY outcome

Timeframe: Day 28

Population: ITT with data at visit

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=117 eyes AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=116 eyes AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=118 eyes AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Pre-CAE Anesthetized Schirmer Test Score at Day 28	7.2 mm Standard Error 0.53	7.9 mm Standard Error 0.53	7.7 mm Standard Error 0.53

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 84

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=115 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=114 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=116 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
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	-12.6 mm Standard Error 2.57	-12.4 mm Standard Error 2.58

SECONDARY outcome

Timeframe: Day 84

Population: ITT with data at visit

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=115 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=114 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=116 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 84	36.1 mm Standard Error 2.55	41.8 mm Standard Error 2.57	42.1 mm Standard Error 2.58

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 28

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=118 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=119 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=119 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
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	-6.6 mm Standard Error 2.39	-6.6 mm Standard Error 2.41

SECONDARY outcome

Timeframe: Day 28

Population: ITT with data at visit

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=118 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=119 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=119 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 28	43.0 mm Standard Error 2.39	48.0 mm Standard Error 2.39	48.0 mm Standard Error 2.41

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 84

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=103 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=97 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=94 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
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	-8.9 mm Standard Error 2.85	-12.1 mm Standard Error 2.93

SECONDARY outcome

Timeframe: Day 84

Population: ITT with data at visit

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=103 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=97 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=94 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Post-CAE Pain Score on a Visual Analogue Scale at Day 84	50.0 mm Standard Error 2.77	58.7 mm Standard Error 2.85	55.5 mm Standard Error 2.93

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 28

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=104 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=97 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=101 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
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	-7.2 mm Standard Error 2.70	-6.4 mm Standard Error 2.71

SECONDARY outcome

Timeframe: Day 28

Population: ITT with data at visit

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=104 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=97 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=101 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Post-CAE Pain Score on a Visual Analogue Scale at Day 28	59.7 mm Standard Error 2.64	60.0 mm Standard Error 2.70	60.8 mm Standard Error 2.71

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 28

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=118 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=119 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=117 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 28	-12.9 mm Standard Error 1.70	-9.3 mm Standard Error 1.69	-5.0 mm Standard Error 1.72

SECONDARY outcome

Timeframe: Day 28

Population: ITT with data at visit

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=118 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=119 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=118 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 28	62.8 mm Standard Error 1.70	66.5 mm Standard Error 1.69	70.8 mm Standard Error 1.72

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 84

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=115 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=114 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=115 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 84	-17.2 mm Standard Error 2.09	-9.5 mm Standard Error 2.09	-8.3 mm Standard Error 2.12

SECONDARY outcome

Timeframe: Day 84

Population: ITT with data at visit

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=115 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=114 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=116 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 84	58.6 mm Standard Error 2.09	66.3 mm Standard Error 2.09	67.5 mm Standard Error 2.12

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 28

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=117 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=118 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=119 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
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	-8.2 mm Standard Error 1.90	-7.8 mm Standard Error 1.91

SECONDARY outcome

Timeframe: Day 28

Population: ITT with data at visit

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=117 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=118 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=119 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 28	63.4 mm Standard Error 1.91	66.5 mm Standard Error 1.90	66.9 mm Standard Error 1.91

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 84

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=115 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=114 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=116 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
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 2.20	-11.5 mm Standard Error 2.21	-10.8 mm Standard Error 2.22

SECONDARY outcome

Timeframe: Day 84

Population: ITT with data at visit

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=115 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=114 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=116 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 84	57.4 mm Standard Error 2.20	63.0 mm Standard Error 2.21	63.7 mm Standard Error 2.22

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 14

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=120 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=120 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=124 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
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	-8.2 mm Standard Error 1.92	-10.7 mm Standard Error 1.90

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 28

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=117 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=116 eyes AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=118 eyes AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
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	-0.4 score on a scale Standard Deviation 1.02	-0.3 score on a scale Standard Deviation 1.11

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 84

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=115 eyes AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=114 eyes AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=116 eyes AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
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	-0.5 score on a scale Standard Deviation 1.16	-0.5 score on a scale Standard Deviation 1.34

SECONDARY outcome

Timeframe: Day 14

Population: ITT with data at visit

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=120 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=120 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=124 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Pre-CAE Ocular Discomfort Score (ODS) on a Visual Analogue Scale at Day 14	63.0 mm Standard Error 1.92	64.8 mm Standard Error 1.92	62.4 mm Standard Error 1.90

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 14

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=120 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=120 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=124 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
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	-1.8 mm Standard Error 2.14	-6.1 mm Standard Error 2.11

SECONDARY outcome

Timeframe: Day 14

Population: ITT with data at visit

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=120 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=120 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=124 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Pre-CAE Pain Score on a Visual Analogue Scale at Day 14	50.3 mm Standard Error 2.13	52.8 mm Standard Error 2.14	48.5 mm Standard Error 2.11

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 14

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=120 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=120 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=123 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Change From Baseline in Pre-CAE Global SANDE Questionnaire Score at Day 14	-7.4 mm Standard Error 1.50	-5.9 mm Standard Error 1.51	-2.9 mm Standard Error 1.50

SECONDARY outcome

Timeframe: Day 14

Population: ITT with data at visit

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=120 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=120 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=124 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Pre-CAE Global SANDE Questionnaire Score at Day 14	68.3 mm Standard Error 1.50	69.8 mm Standard Error 1.51	72.8 mm Standard Error 1.50

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 14

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=120 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=120 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=123 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
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	-4.9 mm Standard Error 1.56	-4.9 mm Standard Error 1.56

SECONDARY outcome

Timeframe: Day 14

Population: ITT with data at visit

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=120 Participants AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=120 Participants AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=123 Participants AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
Least Squares Mean Pre-CAE Eye Dryness Score on a Visual Analogue Scale at Day 14	65.7 mm Standard Error 1.56	69.7 mm Standard Error 1.56	69.7 mm Standard Error 1.56

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 84

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=115 eyes AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=114 eyes AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=116 eyes AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
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	13.2 percentage of subjects	12.1 percentage of subjects

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 28

Population: ITT with data at both visit

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=117 eyes AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=116 eyes AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=118 eyes AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
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	9.5 percentage of subjects	13.6 percentage of subjects

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 28

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=117 eyes AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=116 eyes AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=118 eyes AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
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	9.5 percentage of subjects	7.6 percentage of subjects

SECONDARY outcome

Timeframe: Baseline (Day 1) (pre-treatment), Day 84

Population: ITT with data at both visits

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.

Outcome measures

Measure	AR-15512 Ophthalmic Solution Higher Dose n=115 eyes AR-15512 Ophthalmic Solution 0.003%, one drop in each eye twice daily for 84 days. Both eyes were treated.	AR-15512 Ophthalmic Solution Lower Dose n=114 eyes AR-15512 Ophthalmic Solution 0.0014%, one drop in each eye twice daily for 84 days. Both eyes were treated.	Vehicle n=116 eyes AR-15512 Ophthalmic Solution Vehicle, one drop in each eye twice daily for 84 days. Both eyes were treated.
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	13.2 percentage of subjects	11.2 percentage of subjects

Adverse Events

Pretreatment

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

AR-15512 Ophthalmic Solution Higher Dose - Ocular

Serious events: 0 serious events

Other events: 53 other events

Deaths: 0 deaths

AR-15512 Ophthalmic Solution Higher Dose - Nonocular

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

AR-15512 Ophthalmic Solution Lower Dose - Ocular

Serious events: 0 serious events

Other events: 45 other events

Deaths: 0 deaths

AR-15512 Ophthalmic Solution Lower Dose - Nonocular

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Vehicle - Ocular

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Vehicle - Nonocular

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pretreatment n=369 participants at risk AEs reported in this group occurred prior to treatment with the study drug.	AR-15512 Ophthalmic Solution Higher Dose - Ocular n=122 participants at risk AEs reported in this group occurred during the AR-15512 Ophthalmic Solution 0.003% treatment period.	AR-15512 Ophthalmic Solution Higher Dose - Nonocular n=122 participants at risk AEs reported in this group occurred during the AR-15512 Ophthalmic Solution 0.003% treatment period.	AR-15512 Ophthalmic Solution Lower Dose - Ocular n=121 participants at risk AEs reported in this group occurred during the AR-15512 Ophthalmic Solution 0.0014% treatment period.	AR-15512 Ophthalmic Solution Lower Dose - Nonocular n=121 participants at risk AEs reported in this group occurred during the AR-15512 Ophthalmic Solution 0.0014% treatment period.	Vehicle - Ocular n=126 participants at risk AEs reported in this group occurred during the Vehicle treatment period.	Vehicle - Nonocular n=126 participants at risk AEs reported in this group occurred during the Vehicle treatment period.
Infections and infestations Clostridium difficile infection	0.00% 0/369 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/122 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/122 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/121 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.83% 1/121 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/126 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/126 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.
Infections and infestations Corona virus infection	0.00% 0/369 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/122 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/122 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/121 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/121 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/126 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.79% 1/126 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/369 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/122 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/122 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/121 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/121 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/126 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.79% 1/126 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.
Vascular disorders Peripheral embolism	0.00% 0/369 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/122 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.82% 1/122 • Number of events 1 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/121 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/121 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/126 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/126 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.

Other adverse events

Measure	Pretreatment n=369 participants at risk AEs reported in this group occurred prior to treatment with the study drug.	AR-15512 Ophthalmic Solution Higher Dose - Ocular n=122 participants at risk AEs reported in this group occurred during the AR-15512 Ophthalmic Solution 0.003% treatment period.	AR-15512 Ophthalmic Solution Higher Dose - Nonocular n=122 participants at risk AEs reported in this group occurred during the AR-15512 Ophthalmic Solution 0.003% treatment period.	AR-15512 Ophthalmic Solution Lower Dose - Ocular n=121 participants at risk AEs reported in this group occurred during the AR-15512 Ophthalmic Solution 0.0014% treatment period.	AR-15512 Ophthalmic Solution Lower Dose - Nonocular n=121 participants at risk AEs reported in this group occurred during the AR-15512 Ophthalmic Solution 0.0014% treatment period.	Vehicle - Ocular n=126 participants at risk AEs reported in this group occurred during the Vehicle treatment period.	Vehicle - Nonocular n=126 participants at risk AEs reported in this group occurred during the Vehicle treatment period.
General disorders Instillation site pain	3.0% 11/369 • Number of events 11 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	43.4% 53/122 • Number of events 54 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/122 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	37.2% 45/121 • Number of events 45 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/121 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	3.2% 4/126 • Number of events 4 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.	0.00% 0/126 • An adverse event was (AE) defined as any untoward medical occurrence associated with the administration of the drug in humans, whether or not considered drug related. AE's were collected from time of consent until study exit, approximately 14 weeks. The safety population includes all randomized subjects who have received at least one dose of the investigational product. AEs were obtained through solicited and spontaneous comments from subjects and through observations by the Investigator. The Other (Not Including Serious) Adverse Event table reports only the AEs that occurred above a 5% threshold in one or more arms.

Additional Information

Scientific Advisor, Clinical Research and Development

Alcon Research, LLC

Phone: 1-888-451-3937

Email: alcon.medinfo@alcon.com

Results disclosure agreements

• Principal investigator is a sponsor employee Sponsor reserves the right of prior review of any publication or presentation of information related to the study.
• Publication restrictions are in place

Restriction type: OTHER