Trial Outcomes & Findings for Study Evaluating the Safety and Efficacy of AR-15512 (NCT NCT05285644)

NCT ID: NCT05285644

Last Updated: 2025-07-23

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 465 participants
• Primary outcome timeframe: Baseline (Day 1) pre-drop; Day 14 post-drop
• Results posted on: 2025-07-23

Participant Flow

Participants were recruited from 23 investigative sites located in the United States.

This reporting group includes all randomized participants.

Unit of analysis: eyes

Participant milestones

Measure	0.003% AR-15512 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 90 days	AR-15512 Vehicle AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 90 days
Overall Study STARTED	230 460	235 470
Overall Study ITT Population	230 460	235 470
Overall Study Safety Population	230 460	235 470
Overall Study COMPLETED	210 420	213 426
Overall Study NOT COMPLETED	20 40	22 44

Reasons for withdrawal

Measure	0.003% AR-15512 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 90 days	AR-15512 Vehicle AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 90 days
Overall Study Adverse Event	3	3
Overall Study Withdrawal of Consent	2	5
Overall Study Noncompliance	0	4
Overall Study Lost to Follow-up	4	6
Overall Study Disallowed Concurrent Medication	1	1
Overall Study Investigator Decision	2	0
Overall Study Protocol Deviation	1	0
Overall Study As specified in the Clinical Study Report	7	3

Baseline Characteristics

Study Evaluating the Safety and Efficacy of AR-15512

Baseline characteristics by cohort

Measure	0.003% AR-15512 n=230 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 90 days	AR-15512 Vehicle n=235 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 90 days	Total n=465 Participants Total of all reporting groups
Age, Continuous	59.5 years STANDARD_DEVIATION 13.04 • n=5 Participants	59.6 years STANDARD_DEVIATION 13.43 • n=7 Participants	59.6 years STANDARD_DEVIATION 13.23 • n=5 Participants
Sex: Female, Male Female	173 Participants n=5 Participants	180 Participants n=7 Participants	353 Participants n=5 Participants
Sex: Female, Male Male	57 Participants n=5 Participants	55 Participants n=7 Participants	112 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	31 Participants n=5 Participants	34 Participants n=7 Participants	65 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	199 Participants n=5 Participants	201 Participants n=7 Participants	400 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian / Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	24 Participants n=5 Participants	21 Participants n=7 Participants	45 Participants n=5 Participants
Race/Ethnicity, Customized Black / African American	35 Participants n=5 Participants	32 Participants n=7 Participants	67 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White	168 Participants n=5 Participants	179 Participants n=7 Participants	347 Participants n=5 Participants
Race/Ethnicity, Customized Multi-racial	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	230 participants n=5 Participants	235 participants n=7 Participants	465 participants n=5 Participants
Unanesthetized Schirmer Test Pre-Drop at Baseline (Day 1)	6.2 milllimeter STANDARD_DEVIATION 5.49 • n=5 Participants	5.9 milllimeter STANDARD_DEVIATION 5.41 • n=7 Participants	6.1 milllimeter STANDARD_DEVIATION 5.45 • n=5 Participants
Global SANDE Score at Baseline (Day 1)	72.7 millimeter STANDARD_DEVIATION 12.16 • n=5 Participants	72.7 millimeter STANDARD_DEVIATION 11.74 • n=7 Participants	72.7 millimeter STANDARD_DEVIATION 11.94 • n=5 Participants
SANDE Frequency Score at Baseline (Day 1)	75.2 millimeter STANDARD_DEVIATION 13.77 • n=5 Participants	75.0 millimeter STANDARD_DEVIATION 13.74 • n=7 Participants	75.1 millimeter STANDARD_DEVIATION 13.74 • n=5 Participants
SANDE Severity Score at Baseline (Day 1)	71.1 millimeter STANDARD_DEVIATION 13.28 • n=5 Participants	71.3 millimeter STANDARD_DEVIATION 12.64 • n=7 Participants	71.2 millimeter STANDARD_DEVIATION 12.95 • n=5 Participants
Eye Dryness Score at Baseline (Day 1)	72.8 millimeter STANDARD_DEVIATION 14.77 • n=5 Participants	71.5 millimeter STANDARD_DEVIATION 13.54 • n=7 Participants	72.2 millimeter STANDARD_DEVIATION 14.16 • n=5 Participants
Ocular Discomfort Score at Baseline (Day 1)	74.4 millimeter STANDARD_DEVIATION 12.67 • n=5 Participants	73.4 millimeter STANDARD_DEVIATION 12.11 • n=7 Participants	73.9 millimeter STANDARD_DEVIATION 12.39 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) pre-drop; Day 14 post-drop

Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.

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.

Outcome measures

Measure	0.003% AR-15512 n=230 eyes 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 90 days	AR-15512 Vehicle n=235 eyes AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 90 days
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	8.2 percentage of subjects

SECONDARY outcome

Timeframe: Baseline (Day 1); Day 28

Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.

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).

Outcome measures

Measure	0.003% AR-15512 n=230 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 90 days	AR-15512 Vehicle n=235 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 90 days
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	-14.7 millimeter Standard Error 1.58

SECONDARY outcome

Timeframe: Baseline (Day 1) pre-drop; Day 14 post-drop

Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.

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.

Outcome measures

Measure	0.003% AR-15512 n=230 eyes 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 90 days	AR-15512 Vehicle n=235 eyes AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 90 days
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	2.6 millimeter Standard Error 0.54

SECONDARY outcome

Timeframe: Baseline (Day 1) pre-drop; Day 1 post-drop

Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.

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.

Outcome measures

Measure	0.003% AR-15512 n=230 eyes 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 90 days	AR-15512 Vehicle n=235 eyes AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 90 days
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	9.4 percentage of subjects

SECONDARY outcome

Timeframe: Baseline (Day 1) pre-drop; Day 1 post-drop

Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.

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.

Outcome measures

Measure	0.003% AR-15512 n=230 eyes 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 90 days	AR-15512 Vehicle n=235 eyes AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 90 days
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	2.7 millimeter Standard Deviation 0.52

SECONDARY outcome

Timeframe: Baseline (Day 1) pre-drop; Day 90 post-drop

Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.

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.

Outcome measures

Measure	0.003% AR-15512 n=230 eyes 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 90 days	AR-15512 Vehicle n=235 eyes AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 90 days
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	13.6 percentage of subjects

SECONDARY outcome

Timeframe: Baseline (Day 1) pre-drop; Day 90 post-drop

Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.

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.

Outcome measures

Measure	0.003% AR-15512 n=230 eyes 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 90 days	AR-15512 Vehicle n=235 eyes AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 90 days
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	3.1 millimeter Standard Error 0.57

SECONDARY outcome

Timeframe: Baseline (Day 1); Day 90

Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.

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).

Outcome measures

Measure	0.003% AR-15512 n=230 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 90 days	AR-15512 Vehicle n=235 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 90 days
Least Squares Mean Change From Baseline in Global SANDE Score on Day 90	-23.5 millimeter Standard Error 1.78	-20.7 millimeter Standard Error 1.77

SECONDARY outcome

Timeframe: Baseline (Day 1); Day 90

Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.

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.

Outcome measures

Measure	0.003% AR-15512 n=230 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 90 days	AR-15512 Vehicle n=235 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 90 days
Least Squares Mean Change From Baseline in SANDE Frequency Score on Day 90	-22.8 millimeter Standard Error 1.89	-20.1 millimeter Standard Error 1.89

SECONDARY outcome

Timeframe: Baseline (Day 1); Day 90

Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.

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.

Outcome measures

Measure	0.003% AR-15512 n=230 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 90 days	AR-15512 Vehicle n=235 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 90 days
Least Squares Mean Change From Baseline in SANDE Severity Score on Day 90	-23.1 millimeter Standard Error 1.87	-20.5 millimeter Standard Error 1.84

SECONDARY outcome

Timeframe: Baseline (Day 1); Day 90

Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.

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.

Outcome measures

Measure	0.003% AR-15512 n=230 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 90 days	AR-15512 Vehicle n=235 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 90 days
Least Squares Mean Change From Baseline in Eye Dryness Score (EDS) on Day 90	-22.5 millimeter Standard Error 1.89	-19.1 millimeter Standard Error 1.84

SECONDARY outcome

Timeframe: Baseline (Day 1); Day 90

Population: ITT population comprising all randomized subjects. This analysis uses multiple imputation methodology.

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.

Outcome measures

Measure	0.003% AR-15512 n=230 Participants 0.003% AR-15512 ophthalmic solution, one drop in each eye twice a day for 90 days	AR-15512 Vehicle n=235 Participants AR-15512 vehicle ophthalmic solution, one drop in each eye twice a day for 90 days
Least Squares Mean Change From Baseline in Ocular Discomfort Score (ODS) on Day 90	-32.2 millimeter Standard Error 2.06	-28.2 millimeter Standard Error 2.04

Adverse Events

Pretreatment

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

0.003% AR-15512 Ocular

Serious events: 0 serious events

Other events: 120 other events

Deaths: 0 deaths

0.003% AR-15512 Nonocular

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

AR-15512 Vehicle Ocular

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

AR-15512 Vehicle Nonocular

Serious events: 6 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Pretreatment n=465 participants at risk AEs reported in this group occurred prior to treatment with the study drug and include the 2-week vehicle run-in.	0.003% AR-15512 Ocular n=230 participants at risk AEs reported in this group occurred during the 0.003% AR-15512 ophthalmic solution treatment period.	0.003% AR-15512 Nonocular n=230 participants at risk AEs reported in this group occurred during the 0.003% AR-15512 ophthalmic solution treatment period.	AR-15512 Vehicle Ocular n=235 participants at risk AEs reported in this group occurred during the AR-15512 vehicle ophthalmic solution treatment period.	AR-15512 Vehicle Nonocular n=235 participants at risk AEs reported in this group occurred during the AR-15512 vehicle ophthalmic solution treatment period.
Cardiac disorders Coronary artery occlusion	0.00% 0/465 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/230 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.43% 1/235 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.
Gastrointestinal disorders Constipation	0.00% 0/465 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/230 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.43% 1/235 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.
Gastrointestinal disorders Haemorrhoidal haemorrhage	0.00% 0/465 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/230 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.43% 1/235 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.
Gastrointestinal disorders Volvulus	0.00% 0/465 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/230 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.43% 1/235 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.
Infections and infestations Norovirus infection	0.00% 0/465 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/230 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.43% 1/235 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.
Infections and infestations Pneumonia influenzal	0.00% 0/465 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/230 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.43% 1/235 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.
Injury, poisoning and procedural complications Cartilage injury	0.00% 0/465 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.43% 1/230 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/235 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/465 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/230 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.43% 1/235 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.
Nervous system disorders Migraine	0.00% 0/465 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/230 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.43% 1/235 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.
Nervous system disorders Seizure	0.22% 1/465 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/230 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/235 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.
Psychiatric disorders Alcohol withdrawal syndrome	0.00% 0/465 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.00% 0/230 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	0.43% 1/235 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.

Other adverse events

Measure	Pretreatment n=465 participants at risk AEs reported in this group occurred prior to treatment with the study drug and include the 2-week vehicle run-in.	0.003% AR-15512 Ocular n=230 participants at risk AEs reported in this group occurred during the 0.003% AR-15512 ophthalmic solution treatment period.	0.003% AR-15512 Nonocular n=230 participants at risk AEs reported in this group occurred during the 0.003% AR-15512 ophthalmic solution treatment period.	AR-15512 Vehicle Ocular n=235 participants at risk AEs reported in this group occurred during the AR-15512 vehicle ophthalmic solution treatment period.	AR-15512 Vehicle Nonocular n=235 participants at risk AEs reported in this group occurred during the AR-15512 vehicle ophthalmic solution treatment period.
General disorders Instillation site pain	0.86% 4/465 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	52.2% 120/230 • Number of events 125 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	4.3% 10/235 • Number of events 10 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.	— 0/0 • 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 15 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. All participants were monitored for serious and other ocular and nonocular AEs. All-Cause Mortality was not monitored for the ocular arms. However, the nonocular AE arms were not considered at Risk for ocular adverse event terms as the arms are reporting nonocular-specific AEs. Similarly, the ocular AE arms were not considered at Risk for nonocular adverse event terms as the arms are reporting ocular-specific AEs.

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