Trial Outcomes & Findings for Study Comparing the Safety and Efficacy of BOL-303259-X to Latanoprost in Subjects With Glaucoma or Ocular Hypertension (NCT NCT01223378)

Last Updated: 2018-07-24

Results Overview

Determine the most effective drug concentration(s) of BOL-303259-X in the reduction of intraocular pressure (IOP) and compared to latanoprost

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

413 participants

Primary outcome timeframe

Baseline and Visit 6 (Day 28)

Results posted on

2018-07-24

Participant Flow

First subject enrolled on 13 Dec 2010, Last subject exited on 20 Dec 2011. This study was conducted at 23 clinical sites. US \[15 sites\], Bulgaria \[3 sites\], Poland \[3 sites\], and Czech Republic \[2 sites\]).

Subjects who were currently under treatment with an IOP-lowering medication at Visit 1 were required to discontinue the IOP medication during the washout period (minimum of 28 days) between Visit 1 and Visit 3.

Participant milestones

Participant milestones
Measure	BOL-303259-X 0.006% ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.006%, once daily (QD) 28 days	BOL-303259-X 0.012% ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.012%, once daily (QD) 28 days	BOL-303259-X 0.024% ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.024%, once daily (QD) 28 days	BOL-303259-X 0.040% ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.040%, once daily (QD) 28 days	Latanoprost ophthalmic solution Latanoprost: 0.005% ophthalmic solution, QD 28 days
Overall Study STARTED	82	85	83	81	82
Overall Study COMPLETED	76	81	80	80	79
Overall Study NOT COMPLETED	6	4	3	1	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study Comparing the Safety and Efficacy of BOL-303259-X to Latanoprost in Subjects With Glaucoma or Ocular Hypertension

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BOL-303259-X 0.006% n=82 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.006%, once daily (QD) 28 days	BOL-303259-X 0.012% n=85 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.012%, once daily (QD) 28 days	BOL-303259-X 0.024% n=83 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.024%, once daily (QD) 28 days	BOL-303259-X 0.040% n=81 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.040%, once daily (QD) 28 days	Latanoprost n=82 Participants ophthalmic solution Latanoprost: 0.005% ophthalmic solution, QD 28 days	Total n=413 Participants Total of all reporting groups
Age, Continuous	60.9 years STANDARD_DEVIATION 11.39 • n=5 Participants	61.6 years STANDARD_DEVIATION 9.58 • n=7 Participants	60.8 years STANDARD_DEVIATION 11.47 • n=5 Participants	60.3 years STANDARD_DEVIATION 12.89 • n=4 Participants	61.2 years STANDARD_DEVIATION 11.92 • n=21 Participants	61.0 years STANDARD_DEVIATION 11.44 • n=10 Participants
Sex: Female, Male Female	56 Participants n=5 Participants	46 Participants n=7 Participants	57 Participants n=5 Participants	43 Participants n=4 Participants	53 Participants n=21 Participants	255 Participants n=10 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	39 Participants n=7 Participants	26 Participants n=5 Participants	38 Participants n=4 Participants	29 Participants n=21 Participants	158 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants	6 Participants n=4 Participants	11 Participants n=21 Participants	32 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	77 Participants n=5 Participants	83 Participants n=7 Participants	75 Participants n=5 Participants	75 Participants n=4 Participants	71 Participants n=21 Participants	381 Participants n=10 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	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	21 Participants n=5 Participants	23 Participants n=7 Participants	21 Participants n=5 Participants	23 Participants n=4 Participants	16 Participants n=21 Participants	104 Participants n=10 Participants
Race (NIH/OMB) White	61 Participants n=5 Participants	61 Participants n=7 Participants	62 Participants n=5 Participants	56 Participants n=4 Participants	66 Participants n=21 Participants	306 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants

PRIMARY outcome

Timeframe: Baseline and Visit 6 (Day 28)

Population: Intent-to-treat population, observed data (study eye)

Determine the most effective drug concentration(s) of BOL-303259-X in the reduction of intraocular pressure (IOP) and compared to latanoprost

Outcome measures

Outcome measures
Measure	BOL-303259-X 0.006% n=81 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.006%, once daily (QD) 28 days	BOL-303259-X 0.012% n=83 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.012%, once daily (QD) 28 days	BOL-303259-X 0.024% n=83 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.024%, once daily (QD) 28 days	BOL-303259-X 0.040% n=80 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.040%, once daily (QD) 28 days	Latanoprost n=80 Participants ophthalmic solution Latanoprost: 0.005% ophthalmic solution, QD 28 days
Change in Mean Diurnal IOP at Visit 6 (Day 28)	-7.829 mm Hg Standard Deviation 2.823	-8.295 mm Hg Standard Deviation 2.864	-8.952 mm Hg Standard Deviation 3.337	-8.894 mm Hg Standard Deviation 2.666	-7.800 mm Hg Standard Deviation 2.834

SECONDARY outcome

Timeframe: Baseline and Visit 4 (Day 7), Visit 5 (day 14), and Visit 7 (Day 29)

Population: Intent-to-treat population, observed data (study eye)

Determine the most effective drug concentration(s) of BOL-303259-X in the reduction of intraocular pressure (IOP) and compared to latanoprost

Outcome measures

Outcome measures
Measure	BOL-303259-X 0.006% n=79 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.006%, once daily (QD) 28 days	BOL-303259-X 0.012% n=82 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.012%, once daily (QD) 28 days	BOL-303259-X 0.024% n=81 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.024%, once daily (QD) 28 days	BOL-303259-X 0.040% n=80 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.040%, once daily (QD) 28 days	Latanoprost n=80 Participants ophthalmic solution Latanoprost: 0.005% ophthalmic solution, QD 28 days
Change in Mean Diurnal IOP at Visits 4,5, and 7 Visit 4 (Day 7)	-6.850 mm Hg Standard Deviation 2.768	-7.707 mm Hg Standard Deviation 3.192	-8.230 mm Hg Standard Deviation 3.286	-8.456 mm Hg Standard Deviation 2.892	-7.325 mm Hg Standard Deviation 2.699
Change in Mean Diurnal IOP at Visits 4,5, and 7 Visit 5 (Day 14)	-7.607 mm Hg Standard Deviation 2.204	-7.934 mm Hg Standard Deviation 3.065	-8.859 mm Hg Standard Deviation 3.300	-8.606 mm Hg Standard Deviation 2.878	-7.719 mm Hg Standard Deviation 3.035
Change in Mean Diurnal IOP at Visits 4,5, and 7 Visit 7 (Day 29)	-6.188 mm Hg Standard Deviation 2.782	-6.202 mm Hg Standard Deviation 3.001	-7.177 mm Hg Standard Deviation 3.615	-6.846 mm Hg Standard Deviation 3.135	-6.276 mm Hg Standard Deviation 2.941

SECONDARY outcome

Timeframe: Visit 4 (Day 7), Visit 5 (day 14), Visit 6 (Day 28) and Visit 7 (Day 29)

Population: Intent-to-treat population, observed data (study eye)

Determine the number of subjects with mean diurnal IOP \</=18 mm Hg with BOL-303259-X versus latanoprost ophthalmic solution

Outcome measures

Outcome measures
Measure	BOL-303259-X 0.006% n=82 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.006%, once daily (QD) 28 days	BOL-303259-X 0.012% n=85 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.012%, once daily (QD) 28 days	BOL-303259-X 0.024% n=83 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.024%, once daily (QD) 28 days	BOL-303259-X 0.040% n=81 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.040%, once daily (QD) 28 days	Latanoprost n=82 Participants ophthalmic solution Latanoprost: 0.005% ophthalmic solution, QD 28 days
IOP </=18mm Hg Visit 4 (Day 7)	30 Participants	37 Participants	47 Participants	46 Participants	29 Participants
IOP </=18mm Hg Visit 5 (Day 14)	34 Participants	42 Participants	52 Participants	45 Participants	39 Participants
IOP </=18mm Hg Visit 6 (Day 28)	41 Participants	44 Participants	57 Participants	51 Participants	38 Participants
IOP </=18mm Hg Visit 7 (Day 29)	25 Participants	24 Participants	37 Participants	25 Participants	23 Participants

SECONDARY outcome

Timeframe: baseline and Visit 6 (Day 28)

Population: Intent to treat, data as observed (study eye)

The change in the observed mean study eye IOP from baseline (Visit 3, Day 1) at specified time points (8 AM, 12 PM, 4 PM) at Visit 6 (Day 28)

Outcome measures

Outcome measures
Measure	BOL-303259-X 0.006% n=82 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.006%, once daily (QD) 28 days	BOL-303259-X 0.012% n=85 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.012%, once daily (QD) 28 days	BOL-303259-X 0.024% n=83 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.024%, once daily (QD) 28 days	BOL-303259-X 0.040% n=81 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.040%, once daily (QD) 28 days	Latanoprost n=82 Participants ophthalmic solution Latanoprost: 0.005% ophthalmic solution, QD 28 days
Change in IOP at Specified Time Points (8 AM, 12 PM, 4 PM) at Visit 6 (Day 28) Change from Baseline (8 am)	-8.42 mm Hg Standard Deviation 3.69	-8.91 mm Hg Standard Deviation 3.24	-9.46 mm Hg Standard Deviation 4.01	-9.61 mm Hg Standard Deviation 2.95	-8.76 mm Hg Standard Deviation 3.24
Change in IOP at Specified Time Points (8 AM, 12 PM, 4 PM) at Visit 6 (Day 28) Change from Baseline (12 pm)	-7.82 mm Hg Standard Deviation 3.34	-8.33 mm Hg Standard Deviation 3.35	-8.98 mm Hg Standard Deviation 3.50	-8.60 mm Hg Standard Deviation 3.23	-7.63 mm Hg Standard Deviation 3.55
Change in IOP at Specified Time Points (8 AM, 12 PM, 4 PM) at Visit 6 (Day 28) Change from Baseline (4 pm)	-7.23 mm Hg Standard Deviation 2.97	-7.65 mm Hg Standard Deviation 3.37	-8.59 mm Hg Standard Deviation 3.54	-8.47 mm Hg Standard Deviation 3.28	-6.99 mm Hg Standard Deviation 3.52

SECONDARY outcome

Timeframe: baseline and Visits 4, 5 and 7 (Days 7, 14, and 29)

Population: Intent-to-treat, observed data (study eye)

The change in the observed mean study eye IOP from baseline (Visit 3, Day 1) at specified time points (points 8 AM, 12 PM, and 4 PM) at Visits 4, 5, and 7 (Days 7, 14, and 29)

Outcome measures

Outcome measures
Measure	BOL-303259-X 0.006% n=79 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.006%, once daily (QD) 28 days	BOL-303259-X 0.012% n=82 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.012%, once daily (QD) 28 days	BOL-303259-X 0.024% n=81 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.024%, once daily (QD) 28 days	BOL-303259-X 0.040% n=80 Participants ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.040%, once daily (QD) 28 days	Latanoprost n=80 Participants ophthalmic solution Latanoprost: 0.005% ophthalmic solution, QD 28 days
Change in IOP at Specified Time Points (8 AM, 12 PM, 4 PM) at Visits 4, 5, and 7 (Days 7, 14, and 29) Visit 4 (Day 7) (8 am)	-7.203 mm Hg Standard Deviation 3.634	-8.396 mm Hg Standard Deviation 3.935	-8.667 mm Hg Standard Deviation 3.827	-8.869 mm Hg Standard Deviation 3.384	-8.125 mm Hg Standard Deviation 2.826
Change in IOP at Specified Time Points (8 AM, 12 PM, 4 PM) at Visits 4, 5, and 7 (Days 7, 14, and 29) Visit 4 (Day 7) (12 pm)	-6.665 mm Hg Standard Deviation 3.046	-7.823 mm Hg Standard Deviation 3.409	-8.247 mm Hg Standard Deviation 3.643	-8.219 mm Hg Standard Deviation 3.338	-7.200 mm Hg Standard Deviation 3.386
Change in IOP at Specified Time Points (8 AM, 12 PM, 4 PM) at Visits 4, 5, and 7 (Days 7, 14, and 29) Visit 4 (Day 7) (4 pm)	-6.684 mm Hg Standard Deviation 3.246	-6.902 mm Hg Standard Deviation 3.371	-7.778 mm Hg Standard Deviation 3.479	-8.281 mm Hg Standard Deviation 3.172	-6.650 mm Hg Standard Deviation 3.312
Change in IOP at Specified Time Points (8 AM, 12 PM, 4 PM) at Visits 4, 5, and 7 (Days 7, 14, and 29) Visit 5 (Day 14) (8 am)	-8.270 mm Hg Standard Deviation 3.399	-8.538 mm Hg Standard Deviation 3.518	-9.569 mm Hg Standard Deviation 3.597	-9.006 mm Hg Standard Deviation 3.031	-8.519 mm Hg Standard Deviation 3.444
Change in IOP at Specified Time Points (8 AM, 12 PM, 4 PM) at Visits 4, 5, and 7 (Days 7, 14, and 29) Visit 5 (Day 14) (12 pm)	-7.500 mm Hg Standard Deviation 2.653	-8.381 mm Hg Standard Deviation 3.518	-8.700 mm Hg Standard Deviation 3.579	-8.556 mm Hg Standard Deviation 3.529	-7.519 mm Hg Standard Deviation 3.437
Change in IOP at Specified Time Points (8 AM, 12 PM, 4 PM) at Visits 4, 5, and 7 (Days 7, 14, and 29) Visit 5 (Day 14) (4 pm)	-7.053 mm Hg Standard Deviation 2.519	-6.905 mm Hg Standard Deviation 3.354	-8.310 mm Hg Standard Deviation 3.667	-8.256 mm Hg Standard Deviation 3.410	-7.120 mm Hg Standard Deviation 3.744
Change in IOP at Specified Time Points (8 AM, 12 PM, 4 PM) at Visits 4, 5, and 7 (Days 7, 14, and 29) Visit 7 (Day 29) (8 am)	-6.969 mm Hg Standard Deviation 3.245	-6.796 mm Hg Standard Deviation 3.379	-7.675 mm Hg Standard Deviation 4.198	-7.406 mm Hg Standard Deviation 3.26	-7.006 mm Hg Standard Deviation 3.131
Change in IOP at Specified Time Points (8 AM, 12 PM, 4 PM) at Visits 4, 5, and 7 (Days 7, 14, and 29) Visit 7 (Day 29) (12 pm)	-6.039 mm Hg Standard Deviation 3.591	-6.235 mm Hg Standard Deviation 3.626	-7.119 mm Hg Standard Deviation 3.791	-6.791 mm Hg Standard Deviation 3.246	-6.108 mm Hg Standard Deviation 3.228
Change in IOP at Specified Time Points (8 AM, 12 PM, 4 PM) at Visits 4, 5, and 7 (Days 7, 14, and 29) Visit 7 (Day 29) (4 pm)	-5.575 mm Hg Standard Deviation 3.464	-5.574 mm Hg Standard Deviation 3.615	-6.738 mm Hg Standard Deviation 3.769	-6.090 mm Hg Standard Deviation 4.142	-5.715 mm Hg Standard Deviation 3.514

Adverse Events

BOL-303259-X 0.006%

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

BOL-303259-X 0.012%

Serious events: 0 serious events

Other events: 18 other events

Deaths: 0 deaths

BOL-303259-X 0.024%

Serious events: 0 serious events

Other events: 20 other events

Deaths: 0 deaths

BOL-303259-X 0.040%

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Latanoprost

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	BOL-303259-X 0.006% n=82 participants at risk ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.006%, once daily (QD) 28 days	BOL-303259-X 0.012% n=84 participants at risk ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.012%, once daily (QD) 28 days	BOL-303259-X 0.024% n=83 participants at risk ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.024%, once daily (QD) 28 days	BOL-303259-X 0.040% n=81 participants at risk ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.040%, once daily (QD) 28 days	Latanoprost n=82 participants at risk ophthalmic solution Latanoprost: 0.005% ophthalmic solution, QD 28 days
Gastrointestinal disorders Gastric Ulcer Hemorrhage	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Cardiac disorders Acute myocardial infarction	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Gastrointestinal disorders Gastrointestinal Hemorrage	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Gastrointestinal disorders Gastric Ulcer	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.

Other adverse events

Other adverse events
Measure	BOL-303259-X 0.006% n=82 participants at risk ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.006%, once daily (QD) 28 days	BOL-303259-X 0.012% n=84 participants at risk ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.012%, once daily (QD) 28 days	BOL-303259-X 0.024% n=83 participants at risk ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.024%, once daily (QD) 28 days	BOL-303259-X 0.040% n=81 participants at risk ophthalmic solution Experimental: BOL-303259-X: ophthalmic solution, 0.040%, once daily (QD) 28 days	Latanoprost n=82 participants at risk ophthalmic solution Latanoprost: 0.005% ophthalmic solution, QD 28 days
Eye disorders Ocular Hyperemia	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	6.0% 5/84 • Number of events 5 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	2.4% 2/83 • Number of events 2 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	4.9% 4/81 • Number of events 4 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	8.5% 7/82 • Number of events 7 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Conjunctival Hyperemia	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	3.6% 3/84 • Number of events 3 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	4.8% 4/83 • Number of events 4 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	3.7% 3/81 • Number of events 3 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Eye Irritation	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	2.4% 2/84 • Number of events 2 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	3.6% 3/83 • Number of events 3 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	6.2% 5/81 • Number of events 5 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
General disorders Instillation Site Pain	14.6% 12/82 • Number of events 12 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	16.7% 14/84 • Number of events 14 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	12.0% 10/83 • Number of events 10 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	17.3% 14/81 • Number of events 14 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	6.1% 5/82 • Number of events 5 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Punctate Keratitis	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/84 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	2.4% 2/83 • Number of events 2 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	2.5% 2/81 • Number of events 2 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Dry Eye	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	2.4% 2/83 • Number of events 2 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Eye Pruritus	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/83 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Abnormal Sensation in the Eye	2.4% 2/82 • Number of events 2 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Eye Pain	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	2.5% 2/81 • Number of events 2 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Keratopathy	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/84 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Lacrimation Increased	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/83 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/81 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Photophobia	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	2.5% 2/81 • Number of events 2 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Cataract	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Conjunctival Follicles	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Conjunctivitis	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Eye Lid Edema	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Growth of Eyelashes	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/81 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Keratitis	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/84 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Maculopathy	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Photopsia	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/84 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Visual Acuity Reduced	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/83 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Vitreous Floaters	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Instillation Site Erythema	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/83 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/81 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Instillation Site Lacrimation	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/83 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Instillation Site Pruritus	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	2.5% 2/81 • Number of events 2 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Instillation Site Reaction	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/83 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Instillation Site Discomfort	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/83 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Eye disorders Instillation Site Irritation	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	1.2% 1/81 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.
Nervous system disorders Migraine with Aura	1.2% 1/82 • Number of events 1 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/84 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/83 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/81 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.	0.00% 0/82 • The period of observation for collection of AEs extended from the time the subject gave informed consent until the last study visit (Visit 7). The safety population included one less subject in the BOL-303259-X 0.012% group than the ITT population. Hence the safety population included 412 subjects in total whereas the ITT population included 413 in total.

Additional Information

H DeCory, PhD

Bausch & Lomb

Phone: 585-338-8161

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place