Trial Outcomes & Findings for Efficacy and Safety Study of Bimatoprost Sustained-Release (SR) in Participants With Open-angle Glaucoma or Ocular Hypertension (NCT NCT02247804)

NCT ID: NCT02247804

Last Updated: 2020-06-11

Results Overview

IOP is a measurement of the fluid pressure inside the study eye. Measurements were taken at Hours 0 and 2. The study eye is defined as the eye that meets the entry criteria. If both eyes meet the entry criteria, the eye with the higher IOP at Baseline Hour 0 will be selected as the study eye. If both eyes had the same IOP at Hour 0, then the right eye was designated as the study eye. MMRM was used for analyses.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 594 participants
• Primary outcome timeframe: Week 12 (Hour 2)
• Results posted on: 2020-06-11

Participant Flow

Participant milestones

Measure	Bimatoprost SR 15 μg Study Eye: bimatoprost sustained release (SR) 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Bimatoprost SR 10 μg Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Timolol 0.5%: Comparator Study Eye and Non-Study Eye: sham administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
Treatment Period 1 STARTED	198	198	198
Treatment Period 1 Received (Sham or Bimatoprost SR)	193	197	197
Treatment Period 1 COMPLETED	176	194	190
Treatment Period 1 NOT COMPLETED	22	4	8
Treatment Period 2 STARTED	172	191	187
Treatment Period 2 COMPLETED	164	186	179
Treatment Period 2 NOT COMPLETED	8	5	8
Treatment Period 3 STARTED	158	183	177
Treatment Period 3 COMPLETED	147	173	167
Treatment Period 3 NOT COMPLETED	11	10	10

Reasons for withdrawal

Measure	Bimatoprost SR 15 μg Study Eye: bimatoprost sustained release (SR) 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Bimatoprost SR 10 μg Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Timolol 0.5%: Comparator Study Eye and Non-Study Eye: sham administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
Treatment Period 1 Adverse Event	9	2	0
Treatment Period 1 Lack of Efficacy	0	0	2
Treatment Period 1 Lost to Follow-up	1	0	2
Treatment Period 1 Personal Reasons	7	1	2
Treatment Period 1 Protocol Deviation	0	0	1
Treatment Period 1 Randomized but not Treated	5	1	1
Treatment Period 2 Adverse Event	6	3	3
Treatment Period 2 Lack of Efficacy	0	0	1
Treatment Period 2 Lost to Follow-up	0	1	1
Treatment Period 2 Personal Reasons	2	1	1
Treatment Period 2 Reason not Specified	0	0	2
Treatment Period 3 Adverse Event	4	3	3
Treatment Period 3 Lack of Efficacy	0	1	0
Treatment Period 3 Lost to Follow-up	1	2	2
Treatment Period 3 Personal Reasons	4	3	2
Treatment Period 3 Reason not Specified	2	1	3

Baseline Characteristics

Efficacy and Safety Study of Bimatoprost Sustained-Release (SR) in Participants With Open-angle Glaucoma or Ocular Hypertension

Baseline characteristics by cohort

Measure	Bimatoprost SR 15 μg n=198 Participants Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Bimatoprost SR 10 μg n=198 Participants Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Timolol 0.5%: Comparator n=198 Participants Study Eye and Non-Study Eye: sham administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Total n=594 Participants Total of all reporting groups
Age, Continuous	62.5 years STANDARD_DEVIATION 13.0 • n=5 Participants	62.6 years STANDARD_DEVIATION 11.5 • n=7 Participants	62.5 years STANDARD_DEVIATION 11.0 • n=5 Participants	62.5 years STANDARD_DEVIATION 11.9 • n=4 Participants
Sex: Female, Male Female	96 Participants n=5 Participants	86 Participants n=7 Participants	106 Participants n=5 Participants	288 Participants n=4 Participants
Sex: Female, Male Male	102 Participants n=5 Participants	112 Participants n=7 Participants	92 Participants n=5 Participants	306 Participants n=4 Participants
Race/Ethnicity, Customized White	122 Participants n=5 Participants	123 Participants n=7 Participants	130 Participants n=5 Participants	375 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	30 Participants n=5 Participants	31 Participants n=7 Participants	21 Participants n=5 Participants	82 Participants n=4 Participants
Race/Ethnicity, Customized Asian	12 Participants n=5 Participants	17 Participants n=7 Participants	16 Participants n=5 Participants	45 Participants n=4 Participants
Race/Ethnicity, Customized Hispanic	27 Participants n=5 Participants	23 Participants n=7 Participants	25 Participants n=5 Participants	75 Participants n=4 Participants
Race/Ethnicity, Customized Other	6 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	15 Participants n=4 Participants
Race/Ethnicity, Customized Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Intraocular Pressure (IOP) Hour 0	24.76 mm Hg n=5 Participants	24.64 mm Hg n=7 Participants	24.63 mm Hg n=5 Participants	24.68 mm Hg n=4 Participants
Intraocular Pressure (IOP) Hour 2	23.56 mm Hg n=5 Participants	23.29 mm Hg n=7 Participants	23.19 mm Hg n=5 Participants	23.35 mm Hg n=4 Participants

PRIMARY outcome

Timeframe: Baseline (Hours 0 and 2) to Week 12 (Hours 0 and 2)

Population: ITT population was defined as all randomized participants. Number analyzed is the number of participants with evaluable data at the given timepoint.

IOP is a measurement of the fluid pressure inside the study eye. Measurements were taken at Hours 0 and 2. The study eye is defined as the eye that meets the entry criteria. If both eyes meet the entry criteria, the eye with the higher IOP at Baseline Hour 0 will be selected as the study eye. If both eyes had the same IOP at Hour 0, then the right eye was designated as the study eye. A mixed-effects model with repeated measures (MMRM) was used for analyses. A negative change from baseline indicates an improvement and a positive change from baseline indicates a worsening.

Outcome measures

Measure	Bimatoprost SR 10 μg n=198 Participants Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Bimatoprost SR 15 μg n=198 Participants Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Timolol 0.5%: Comparator n=198 Participants Study Eye and Non-Study Eye: sham administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
Change From Baseline in IOP in the Study Eye at Week 12 (Hours 0 and 2) Change from Baseline at Hour 0, Week 12	-6.38 millimeters of mercury (mm Hg) Standard Error 0.28	-6.46 millimeters of mercury (mm Hg) Standard Error 0.29	-6.05 millimeters of mercury (mm Hg) Standard Error 0.28
Change From Baseline in IOP in the Study Eye at Week 12 (Hours 0 and 2) Change from Baseline at Hour 2, Week 12	-6.69 millimeters of mercury (mm Hg) Standard Error 0.25	-7.18 millimeters of mercury (mm Hg) Standard Error 0.26	-6.48 millimeters of mercury (mm Hg) Standard Error 0.25

PRIMARY outcome

Timeframe: Week 2 (Hour 0)

Population: ITT population was defined as all randomized participants. Overall number of participants analyzed is the number of participants with data available for analyses.

IOP is a measurement of the fluid pressure inside the study eye. Measurements were taken at Hours 0 and 2. The study eye is defined as the eye that meets the entry criteria. If both eyes meet the entry criteria, the eye with the higher IOP at Baseline Hour 0 will be selected as the study eye. If both eyes had the same IOP at Hour 0, then the right eye was designated as the study eye. MMRM was used for analyses.

Outcome measures

Measure	Bimatoprost SR 10 μg n=196 Participants Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Bimatoprost SR 15 μg n=191 Participants Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Timolol 0.5%: Comparator n=196 Participants Study Eye and Non-Study Eye: sham administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
IOP in the Study Eye at Week 2 (Hour 0)	17.02 mm Hg Standard Error 0.25	16.82 mm Hg Standard Error 0.25	17.83 mm Hg Standard Error 0.25

PRIMARY outcome

Timeframe: Week 2 (Hour 2)

Population: ITT population was defined as all randomized participants. Overall number of participants analyzed is the number of participants with data available for analyses.

IOP is a measurement of the fluid pressure inside the study eye. Measurements were taken at Hours 0 and 2. The study eye is defined as the eye that meets the entry criteria. If both eyes meet the entry criteria, the eye with the higher IOP at Baseline Hour 0 will be selected as the study eye. If both eyes had the same IOP at Hour 0, then the right eye was designated as the study eye. MMRM was used for analyses.

Outcome measures

Measure	Bimatoprost SR 10 μg n=196 Participants Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Bimatoprost SR 15 μg n=191 Participants Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Timolol 0.5%: Comparator n=196 Participants Study Eye and Non-Study Eye: sham administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
IOP in the Study Eye at Week 2 (Hour 2)	16.42 mm Hg Standard Error 0.22	16.48 mm Hg Standard Error 0.22	17.33 mm Hg Standard Error 0.22

PRIMARY outcome

Timeframe: Week 6 (Hour 0)

Population: ITT population was defined as all randomized participants. Overall number of participants analyzed is the number of participants with data available for analyses.

IOP is a measurement of the fluid pressure inside the study eye. Measurements were taken at Hours 0 and 2. The study eye is defined as the eye that meets the entry criteria. If both eyes meet the entry criteria, the eye with the higher IOP at Baseline Hour 0 will be selected as the study eye. If both eyes had the same IOP at Hour 0, then the right eye was designated as the study eye. MMRM was used for analyses.

Outcome measures

Measure	Bimatoprost SR 10 μg n=197 Participants Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Bimatoprost SR 15 μg n=188 Participants Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Timolol 0.5%: Comparator n=194 Participants Study Eye and Non-Study Eye: sham administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
IOP in the Study Eye at Week 6 (Hour 0)	16.88 mm Hg Standard Error 0.23	17.08 mm Hg Standard Error 0.24	17.71 mm Hg Standard Error 0.24

PRIMARY outcome

Timeframe: Week 6 (Hour 2)

Population: ITT population was defined as all randomized participants. Overall number of participants analyzed is the number of participants with data available for analyses.

IOP is a measurement of the fluid pressure inside the study eye. Measurements were taken at Hours 0 and 2. The study eye is defined as the eye that meets the entry criteria. If both eyes meet the entry criteria, the eye with the higher IOP at Baseline Hour 0 will be selected as the study eye. If both eyes had the same IOP at Hour 0, then the right eye was designated as the study eye. MMRM was used for analyses.

Outcome measures

Measure	Bimatoprost SR 10 μg n=197 Participants Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Bimatoprost SR 15 μg n=187 Participants Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Timolol 0.5%: Comparator n=193 Participants Study Eye and Non-Study Eye: sham administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
IOP in the Study Eye at Week 6 (Hour 2)	16.51 mm Hg Standard Error 0.22	16.62 mm Hg Standard Error 0.23	17.16 mm Hg Standard Error 0.23

PRIMARY outcome

Timeframe: Week 12 (Hour 0)

Population: ITT population was defined as all randomized participants. Overall number of participants analyzed is the number of participants with data available for analyses.

IOP is a measurement of the fluid pressure inside the study eye. Measurements were taken at Hours 0 and 2. The study eye is defined as the eye that meets the entry criteria. If both eyes meet the entry criteria, the eye with the higher IOP at Baseline Hour 0 will be selected as the study eye. If both eyes had the same IOP at Hour 0, then the right eye was designated as the study eye. MMRM was used for analyses.

Outcome measures

Measure	Bimatoprost SR 10 μg n=192 Participants Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Bimatoprost SR 15 μg n=185 Participants Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Timolol 0.5%: Comparator n=191 Participants Study Eye and Non-Study Eye: sham administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
IOP in the Study Eye at Week 12 (Hour 0)	17.61 mm Hg Standard Error 0.28	17.53 mm Hg Standard Error 0.29	17.94 mm Hg Standard Error 0.28

PRIMARY outcome

Timeframe: Week 12 (Hour 2)

Population: ITT population was defined as all randomized participants. Overall number of participants analyzed is the number of participants with data available for analyses.

IOP is a measurement of the fluid pressure inside the study eye. Measurements were taken at Hours 0 and 2. The study eye is defined as the eye that meets the entry criteria. If both eyes meet the entry criteria, the eye with the higher IOP at Baseline Hour 0 will be selected as the study eye. If both eyes had the same IOP at Hour 0, then the right eye was designated as the study eye. MMRM was used for analyses.

Outcome measures

Measure	Bimatoprost SR 10 μg n=192 Participants Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Bimatoprost SR 15 μg n=183 Participants Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Timolol 0.5%: Comparator n=191 Participants Study Eye and Non-Study Eye: sham administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
IOP in the Study Eye at Week 12 (Hour 2)	17.30 mm Hg Standard Error 0.25	16.81 mm Hg Standard Error 0.26	17.51 mm Hg Standard Error 0.25

SECONDARY outcome

Timeframe: Baseline (Hours 0 and 2) to Weeks 2 and 6 (Hours 0 and 2)

Population: ITT population was defined as all randomized participants. Number analyzed is the number of participants with evaluable data at the given timepoint.

IOP is a measurement of the fluid pressure inside the study eye. Measurements were taken at Hours 0 and 2. The study eye is defined as the eye that meets the entry criteria. If both eyes meet the entry criteria, the eye with the higher IOP at Baseline Hour 0 will be selected as the study eye. If both eyes had the same IOP at Hour 0, then the right eye was designated as the study eye. MMRM was used for analyses. A negative change from baseline indicates an improvement and a positive change from baseline indicates a worsening.

Outcome measures

Measure	Bimatoprost SR 10 μg n=198 Participants Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Bimatoprost SR 15 μg n=198 Participants Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Timolol 0.5%: Comparator n=198 Participants Study Eye and Non-Study Eye: sham administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
Change From Baseline in IOP in the Study Eye Change from Baseline at Hour 0, Week 2	-6.97 mm Hg Standard Error 0.25	-7.17 mm Hg Standard Error 0.25	-6.17 mm Hg Standard Error 0.25
Change From Baseline in IOP in the Study Eye Change from Baseline at Hour 2, Week 2	-7.57 mm Hg Standard Error 0.22	-7.52 mm Hg Standard Error 0.22	-6.67 mm Hg Standard Error 0.22
Change From Baseline in IOP in the Study Eye Change from Baseline at Hour 0, Week 6	-7.11 mm Hg Standard Error 0.23	-6.91 mm Hg Standard Error 0.24	-6.29 mm Hg Standard Error 0.24
Change From Baseline in IOP in the Study Eye Change from Baseline at Hour 2, Week 6	-7.48 mm Hg Standard Error 0.22	-7.37 mm Hg Standard Error 0.23	-6.83 mm Hg Standard Error 0.23

Adverse Events

Bimatoprost SR 15 μg

Serious events: 31 serious events

Other events: 143 other events

Deaths: 2 deaths

Bimatoprost SR 10 μg

Serious events: 25 serious events

Other events: 138 other events

Deaths: 1 deaths

Timolol 0.5%: Comparator

Serious events: 18 serious events

Other events: 105 other events

Deaths: 1 deaths

Serious adverse events

Measure	Bimatoprost SR 15 μg n=193 participants at risk Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Bimatoprost SR 10 μg n=197 participants at risk Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Timolol 0.5%: Comparator n=197 participants at risk Study Eye and Non-Study Eye: sham administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
Cardiac disorders Acute myocardial infarction	1.0% 2/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Cardiac disorders Acute coronary syndrome	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Cardiac disorders Cardiac arrest	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Cardiac disorders Myocardial infarction	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Cardiac disorders Atrial fibrillation	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Cardiac disorders Cardiac failure	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Cardiac disorders Bradycardia	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Corneal endothelial cell loss	6.2% 12/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	2.0% 4/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Corneal oedema	1.6% 3/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	1.0% 2/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Iridocyclitis	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Corneal touch	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Macular oedema	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Retinal tear	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Ulcerative keratitis	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Uveitis	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Retinal detachment	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Haemorrhoids	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Small intestinal obstruction	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Gastric ulcer	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Intestinal obstruction	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Umbilical hernia	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Diarrhoea	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Abdominal pain	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Peptic ulcer	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
General disorders Chest pain	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Infections and infestations Clostridium difficile infection	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Infections and infestations Appendicitis perforated	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Infections and infestations Diverticulitis	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Infections and infestations Gastroenteritis	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Infections and infestations Post procedural sepsis	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Infections and infestations Urinary tract infection	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Injury, poisoning and procedural complications Femur fracture	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Injury, poisoning and procedural complications Road traffic accident	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Injury, poisoning and procedural complications Fall	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	1.0% 2/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Injury, poisoning and procedural complications Head injury	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Musculoskeletal and connective tissue disorders Chondrocalcinosis pyrophosphate	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Musculoskeletal and connective tissue disorders Joint instability	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal proliferative breast lesion	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	1.0% 2/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Parathyroid tumour benign	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive breast carcinoma	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer recurrent	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Nervous system disorders Cerebrovascular accident	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	1.0% 2/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Nervous system disorders Cerebral haemorrhage	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Nervous system disorders Embolic stroke	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Nervous system disorders Headache	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Nervous system disorders Trigeminal neuralgia	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Nervous system disorders Sciatica	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Nervous system disorders VIth nerve paralysis	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Renal and urinary disorders Renal failure	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pneumothorax spontaneous	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Vascular disorders Internal haemorrhage	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Vascular disorders Varicose vein	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Vascular disorders Deep vein thrombosis	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Vascular disorders Hypotension	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Gastrointestinal disorders Hiatus hernia	0.52% 1/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.

Other adverse events

Measure	Bimatoprost SR 15 μg n=193 participants at risk Study Eye: bimatoprost SR 15 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Bimatoprost SR 10 μg n=197 participants at risk Study Eye: bimatoprost SR 10 μg administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol vehicle administered once in the morning and once in the evening for up to 20 months. Non-Study Eye: sham administration on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.	Timolol 0.5%: Comparator n=197 participants at risk Study Eye and Non-Study Eye: sham administered on Day 1 (Period 1), Week 16 (Period 2), and Week 32 (Period 3); timolol 0.5% administered once in the morning and once in the evening for up to 20 months.
Eye disorders Conjunctival hyperaemia	38.3% 74/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	30.5% 60/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	23.9% 47/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Foreign body sensation in eyes	16.1% 31/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	11.7% 23/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	6.1% 12/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Eye pain	14.5% 28/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	13.2% 26/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	6.1% 12/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Eye irritation	14.5% 28/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	9.1% 18/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	11.2% 22/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Photophobia	11.9% 23/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	9.6% 19/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	2.0% 4/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Corneal endothelial cell loss	10.4% 20/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	7.1% 14/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Conjunctival haemorrhage	9.8% 19/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	8.6% 17/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	8.1% 16/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Iritis	9.8% 19/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	5.6% 11/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.51% 1/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Dry eye	8.8% 17/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	9.6% 19/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	6.1% 12/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Punctate keratitis	8.3% 16/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	6.1% 12/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	7.1% 14/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Lacrimation increased	6.7% 13/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	5.1% 10/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	6.1% 12/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Vision blurred	6.2% 12/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	5.1% 10/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	5.6% 11/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Corneal oedema	6.2% 12/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	2.5% 5/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	1.0% 2/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Eye disorders Anterior chamber cell	5.7% 11/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	4.6% 9/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	0.00% 0/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Infections and infestations Nasopharyngitis	6.7% 13/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	5.1% 10/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	7.1% 14/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Infections and infestations Influenza	4.1% 8/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	6.6% 13/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	2.0% 4/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Investigations Intraocular pressure increased	6.7% 13/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	10.2% 20/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	3.6% 7/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Nervous system disorders Headache	4.1% 8/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	7.1% 14/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	3.6% 7/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Nervous system disorders Visual field defect	2.1% 4/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	5.1% 10/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	2.5% 5/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.
Vascular disorders Hypertension	8.8% 17/193 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	6.1% 12/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.	4.1% 8/197 • First dose of study drug to last visit (Up to approximately 20 months) Safety population included all participants who received at least 1 dose of study treatment.

Additional Information

Therapeutic Area, Head

Allergan

Phone: 714-246-4500

Email: clinicaltrials@allergan.com

Results disclosure agreements

• Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
• Publication restrictions are in place

Restriction type: OTHER