Trial Outcomes & Findings for A Phase III Study Assessing the Efficacy and Safety of DE-117 Ophthalmic Solution Compared With Timolol Maleate Ophthalmic Solution 0.5% in Subjects With Glaucoma or Ocular Hypertension - Spectrum 3 Study (NCT NCT03691649)

NCT ID: NCT03691649

Last Updated: 2023-08-30

Results Overview

Intraocular Pressure (IOP), the fluid pressure inside the eye was measured with calibrated Goldmann applanation tonometer in millimeters mercury (mmHg) at 3 time points throughout the day. Analysis using Mixed-Effects Model for Repeated Measures (MMRM)

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 426 participants
• Primary outcome timeframe: 08:00, 10:00 and 16:00 at Week 1
• Results posted on: 2023-08-30

Participant Flow

Participant milestones

Measure	DE-117 Ophthalmic Solution Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 months for adult subjects only. DE-117 Ophthalmic Solution: Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 months for adult subjects only.	Timolol Maleate Ophthalmic Solution 0.5% Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 months for adult subjects only. Timolol Maleate Ophthalmic Solution 0.5%: Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 months for adult subjects only.
Double Masked Treatment Period (DMTP) STARTED	212	214
Double Masked Treatment Period (DMTP) Full Analysis Set Participants	212	213
Double Masked Treatment Period (DMTP) Safety Analysis Set Participants	211	215
Double Masked Treatment Period (DMTP) COMPLETED	189	204
Double Masked Treatment Period (DMTP) NOT COMPLETED	23	10
Open Label Treatment Period (OLTP) STARTED	377	0
Open Label Treatment Period (OLTP) COMPLETED	304	0
Open Label Treatment Period (OLTP) NOT COMPLETED	73	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase III Study Assessing the Efficacy and Safety of DE-117 Ophthalmic Solution Compared With Timolol Maleate Ophthalmic Solution 0.5% in Subjects With Glaucoma or Ocular Hypertension - Spectrum 3 Study

Baseline characteristics by cohort

Measure	DE-117 Ophthalmic Solution n=212 Participants Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only DE-117 Ophthalmic Solution: Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only	Timolol Maleate Ophthalmic Solution 0.5% n=213 Participants Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only Timolol Maleate Ophthalmic Solution 0.5%: Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only	Total n=425 Participants Total of all reporting groups
Age, Categorical <=18 years	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	83 Participants n=5 Participants	91 Participants n=7 Participants	174 Participants n=5 Participants
Age, Categorical >=65 years	123 Participants n=5 Participants	115 Participants n=7 Participants	238 Participants n=5 Participants
Age, Continuous	64.7 years STANDARD_DEVIATION 14.91 • n=5 Participants	63.5 years STANDARD_DEVIATION 14.48 • n=7 Participants	64.1 years STANDARD_DEVIATION 14.69 • n=5 Participants
Sex: Female, Male Female	123 Participants n=5 Participants	135 Participants n=7 Participants	258 Participants n=5 Participants
Sex: Female, Male Male	89 Participants n=5 Participants	78 Participants n=7 Participants	167 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	48 Participants n=5 Participants	52 Participants n=7 Participants	100 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	160 Participants n=5 Participants	155 Participants n=7 Participants	315 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment United States	212 Participants n=5 Participants	213 Participants n=7 Participants	425 Participants n=5 Participants

PRIMARY outcome

Timeframe: 08:00, 10:00 and 16:00 at Week 1

Population: Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study medication and provided baseline and at least one post-baseline IOP measurement. The number of analyzed are participants evaluable for the outcome measure at Week 1.

Intraocular Pressure (IOP), the fluid pressure inside the eye was measured with calibrated Goldmann applanation tonometer in millimeters mercury (mmHg) at 3 time points throughout the day. Analysis using Mixed-Effects Model for Repeated Measures (MMRM)

Outcome measures

Measure	DE-117 Ophthalmic Solution n=212 Participants Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only DE-117 Ophthalmic Solution: Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only	Timolol Maleate Ophthalmic Solution 0.5% n=213 Participants Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only Timolol Maleate Ophthalmic Solution 0.5%: Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only
Intraocular Pressure at Week 1 8:00	19.0 mmHg Standard Error 0.22	19.1 mmHg Standard Error 0.21
Intraocular Pressure at Week 1 10:00	18.0 mmHg Standard Error 0.21	18.2 mmHg Standard Error 0.21
Intraocular Pressure at Week 1 16:00	17.5 mmHg Standard Error 0.21	17.9 mmHg Standard Error 0.21

PRIMARY outcome

Timeframe: 08:00, 10:00 and 16:00 at Week 6

Population: Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study medication and provided baseline and at least one post-baseline IOP measurement. The number of analyzed are participants evaluable for the outcome measure at Week 6.

Intraocular Pressure (IOP), the fluid pressure inside the eye was measured with calibrated Goldmann applanation tonometer in millimeters mercury (mmHg) at 3 time points throughout the day. Analysis using Mixed-Effects Model for Repeated Measures (MMRM)

Outcome measures

Measure	DE-117 Ophthalmic Solution n=212 Participants Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only DE-117 Ophthalmic Solution: Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only	Timolol Maleate Ophthalmic Solution 0.5% n=213 Participants Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only Timolol Maleate Ophthalmic Solution 0.5%: Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only
Intraocular Pressure at Week 6 8:00	19.8 mmHg Standard Error 0.20	18.4 mmHg Standard Error 0.20
Intraocular Pressure at Week 6 10:00	18.9 mmHg Standard Error 0.20	18.0 mmHg Standard Error 0.20
Intraocular Pressure at Week 6 16:00	18.5 mmHg Standard Error 0.21	17.7 mmHg Standard Error 0.21

PRIMARY outcome

Timeframe: 08:00, 10:00 and 16:00 at Month 3

Population: Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study medication and provided baseline and at least one post-baseline IOP measurement. The number of analyzed are participants evaluable for the outcome measure at Month 3.

Intraocular Pressure (IOP), the fluid pressure inside the eye was measured with calibrated Goldmann applanation tonometer in millimeters mercury (mmHg) at 3 time points throughout the day. Analysis using Mixed-Effects Model for Repeated Measures (MMRM)

Outcome measures

Measure	DE-117 Ophthalmic Solution n=212 Participants Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only DE-117 Ophthalmic Solution: Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only	Timolol Maleate Ophthalmic Solution 0.5% n=213 Participants Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only Timolol Maleate Ophthalmic Solution 0.5%: Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only
Intraocular Pressure at Month 3 8:00	19.7 mmHg Standard Error 0.24	18.5 mmHg Standard Error 0.24
Intraocular Pressure at Month 3 10:00	18.8 mmHg Standard Error 0.21	17.7 mmHg Standard Error 0.21
Intraocular Pressure at Month 3 16:00	18.6 mmHg Standard Error 0.22	17.8 mmHg Standard Error 0.21

SECONDARY outcome

Timeframe: Month 3

Population: Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study medication and provided baseline and at least one post-baseline IOP measurement. The number of analyzed are participants evaluable for the outcome measure at Month 3.

Mean Diurnal Intraocular Pressure (IOP) at Month 3: Analysis using Mixed-Effects Model for Repeated Measures (MMRM) on observed cases.

Outcome measures

Measure	DE-117 Ophthalmic Solution n=196 Participants Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only DE-117 Ophthalmic Solution: Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only	Timolol Maleate Ophthalmic Solution 0.5% n=203 Participants Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only Timolol Maleate Ophthalmic Solution 0.5%: Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only
Mean Diurnal Intraocular Pressure (IOP) at Month 3 (First Key Secondary Endpoint)	19.0 mmHg Standard Error 0.20	18.0 mmHg Standard Error 0.19

SECONDARY outcome

Timeframe: 08:00, 10:00 and 16:00 at Week 1

Population: Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study medication and provided baseline and at least one post-baseline IOP measurement. The number of analyzed are participants evaluable for the outcome measure at Week 1.

Intraocular Pressure (IOP) at Week 1 with baseline mean diurnal IOP less than 25 mmHg (Second Key Secondary Endpoint)

Outcome measures

Measure	DE-117 Ophthalmic Solution n=140 Participants Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only DE-117 Ophthalmic Solution: Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only	Timolol Maleate Ophthalmic Solution 0.5% n=138 Participants Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only Timolol Maleate Ophthalmic Solution 0.5%: Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only
Intraocular Pressure (IOP) at Week 1 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) 8:00	17.9 mmHg Standard Error 0.25	18.2 mmHg Standard Error 0.25
Intraocular Pressure (IOP) at Week 1 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) 10:00	17.2 mmHg Standard Error 0.24	17.3 mmHg Standard Error 0.24
Intraocular Pressure (IOP) at Week 1 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) 16:00	16.8 mmHg Standard Error 0.25	17.2 mmHg Standard Error 0.25

SECONDARY outcome

Timeframe: 08:00, 10:00 and 16:00 at Week 6

Population: Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study medication and provided baseline and at least one post-baseline IOP measurement. The number of analyzed are participants evaluable for the outcome measure at Week 6.

Intraocular Pressure (IOP) at Week 6 with baseline mean diurnal IOP less than 25 mmHg (Second Key Secondary Endpoint)

Outcome measures

Measure	DE-117 Ophthalmic Solution n=140 Participants Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only DE-117 Ophthalmic Solution: Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only	Timolol Maleate Ophthalmic Solution 0.5% n=138 Participants Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only Timolol Maleate Ophthalmic Solution 0.5%: Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only
Intraocular Pressure (IOP) at Week 6 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) 8:00	18.7 mmHg Standard Error 0.24	17.8 mmHg Standard Error 0.24
Intraocular Pressure (IOP) at Week 6 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) 10:00	18.0 mmHg Standard Error 0.25	17.4 mmHg Standard Error 0.25
Intraocular Pressure (IOP) at Week 6 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) 16:00	17.6 mmHg Standard Error 0.23	17.1 mmHg Standard Error 0.23

SECONDARY outcome

Timeframe: 08:00, 10:00 and 16:00 at Month 3

Population: Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study medication and provided baseline and at least one post-baseline IOP measurement. The number of analyzed are participants evaluable for the outcome measure at Month 3.

Intraocular Pressure (IOP) at Month 3 with baseline mean diurnal IOP less than 25 mmHg (Second Key Secondary Endpoint)

Outcome measures

Measure	DE-117 Ophthalmic Solution n=140 Participants Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only DE-117 Ophthalmic Solution: Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only	Timolol Maleate Ophthalmic Solution 0.5% n=138 Participants Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only Timolol Maleate Ophthalmic Solution 0.5%: Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only
Intraocular Pressure (IOP) at Month 3 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) 8:00	18.6 mmHg Standard Error 0.29	17.7 mmHg Standard Error 0.28
Intraocular Pressure (IOP) at Month 3 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) 10:00	17.8 mmHg Standard Error 0.25	16.9 mmHg Standard Error 0.25
Intraocular Pressure (IOP) at Month 3 With Baseline Mean Diurnal IOP Less Than 25 mmHg (Second Key Secondary Endpoint) 16:00	17.7 mmHg Standard Error 0.25	17.2 mmHg Standard Error 0.25

SECONDARY outcome

Timeframe: Week 1

Population: Full Analysis Set (FAS) included all randomized subjects who received at least one dose of study medication and provided baseline and at least one post-baseline IOP measurement. The number of analyzed are participants evaluable for the outcome measure at Week 1.

Mean Diurnal Intraocular Pressure (IOP) at Week 1: Analysis using Mixed-Effects Model for Repeated Measures (MMRM) on observed cases.

Mean Diurnal IOP at week 1 is defined as the average IOP of all three timepoints (8AM, 10AM and 4PM) at week 1.

Outcome measures

Measure	DE-117 Ophthalmic Solution n=209 Participants Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only DE-117 Ophthalmic Solution: Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only	Timolol Maleate Ophthalmic Solution 0.5% n=210 Participants Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only Timolol Maleate Ophthalmic Solution 0.5%: Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only
Mean Diurnal Intraocular Pressure (IOP) at Week 1 (Third Key Secondary Endpoint)	18.1 mmHg Standard Error 0.19	18.4 mmHg Standard Error 0.19

Adverse Events

DE-117 Ophthalmic Solution (Double Masked Treatment Period)

Serious events: 4 serious events

Other events: 61 other events

Deaths: 0 deaths

Timolol Maleate Ophthalmic Solution 0.5% (Double Masked Treatment Period)

Serious events: 5 serious events

Other events: 47 other events

Deaths: 1 deaths

DE-117 Ophthalmic Solution (Open Label Treatment Period)

Serious events: 12 serious events

Other events: 85 other events

Deaths: 1 deaths

Serious adverse events

Measure	DE-117 Ophthalmic Solution (Double Masked Treatment Period) n=211 participants at risk Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only DE-117 Ophthalmic Solution: Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only	Timolol Maleate Ophthalmic Solution 0.5% (Double Masked Treatment Period) n=215 participants at risk Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only Timolol Maleate Ophthalmic Solution 0.5%: Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only	DE-117 Ophthalmic Solution (Open Label Treatment Period) n=377 participants at risk Topical DE-117 Ophthalmic Solution once daily for 9 months for adult subjects only (Period 2)
Eye disorders Cystoid macular	0.47% 1/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.80% 3/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Hepatobiliary disorders Cholecystitis	0.47% 1/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Metabolism and nutrition disorders Hyperglycemia	0.47% 1/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Infections and infestations Pneumonia	0.47% 1/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.53% 2/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Investigations Influenza Type A test positive	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.47% 1/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Cardiac disorders Atrial fibrillation	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.47% 1/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Ear and labyrinth disorders Vertigo	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.47% 1/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Nervous system disorders Cerebral hemorrhage	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.27% 1/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Cardiac disorders Acute Cardiac event	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.27% 1/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Musculoskeletal and connective tissue disorders Osteoporosis	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.27% 1/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.27% 1/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Renal and urinary disorders Nephrolithiasis	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.27% 1/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine cancer	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.27% 1/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.27% 1/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Nervous system disorders Cerebrovascular accident	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.47% 1/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Nervous system disorders Dizziness	0.47% 1/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.47% 1/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.

Other adverse events

Measure	DE-117 Ophthalmic Solution (Double Masked Treatment Period) n=211 participants at risk Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only DE-117 Ophthalmic Solution: Topical DE-117 Ophthalmic Solution once daily and Vehicle once daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only	Timolol Maleate Ophthalmic Solution 0.5% (Double Masked Treatment Period) n=215 participants at risk Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only Timolol Maleate Ophthalmic Solution 0.5%: Topical Timolol Maleate Ophthalmic Solution 0.5% twice daily for 3 months for all subjects, followed by DE-117 Ophthalmic Solution once daily for additional 9 month for adult subjects only	DE-117 Ophthalmic Solution (Open Label Treatment Period) n=377 participants at risk Topical DE-117 Ophthalmic Solution once daily for 9 months for adult subjects only (Period 2)
Eye disorders Conjunctival hyperaemia	6.2% 13/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	4.7% 10/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	3.2% 12/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Eye disorders Vision blurred	5.2% 11/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	1.4% 3/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	3.7% 14/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Eye disorders Photophobia	4.7% 10/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.47% 1/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	1.1% 4/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Eye disorders Ocular hyperaemia	2.8% 6/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	1.9% 4/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Eye disorders Dry eye	1.9% 4/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.93% 2/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Eye disorders Eye pain	1.9% 4/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	2.3% 5/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	1.6% 6/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Eye disorders Visual impairment	1.9% 4/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Eye disorders Eye irritation	1.4% 3/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	3.7% 8/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	1.1% 4/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Eye disorders Vitreous detachment	1.4% 3/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.47% 1/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Eye disorders Vitreous floaters	1.4% 3/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	1.6% 6/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Eye disorders Growth of eyelashes	0.95% 2/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	1.4% 3/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	1.3% 5/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Eye disorders Macular oedema	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	2.4% 9/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Eye disorders Cystoid macular oedema	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	2.4% 9/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Eye disorders Punctate keratitis	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	1.9% 7/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Eye disorders Conjunctival haemorrhage	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	1.1% 4/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Eye disorders Eyelash changes	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	1.1% 4/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Eye disorders Eyelash hyperpigmentation	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	1.1% 4/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Eye disorders Eyelash thickening	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	1.1% 4/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Infections and infestations Sinusitis	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	1.3% 5/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Infections and infestations Urinary tract infection	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	1.3% 5/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Infections and infestations Upper respiratory tract infection	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	1.4% 3/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	1.1% 4/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Infections and infestations Nasopharyngitis	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	1.9% 4/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
General disorders Instillation site pain	2.4% 5/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	5.6% 12/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Investigations Vital dye staining cornea present	3.3% 7/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	2.3% 5/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	2.1% 8/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Nervous system disorders Headache	1.9% 4/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.93% 2/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.
Vascular disorders Hypertension	0.00% 0/211 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	0.00% 0/215 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.	1.1% 4/377 • Adverse events were collected from the time of informed consent and were followed to resolution or until the subject's participation in the study ended for both Period 1 (Double Masked Treatment Period) at Month 3 and Period 2 (Open Label Treatment Period) at Month 12. Other Adverse Event data is a summary observed at a rate of 1.0% or higher by System Organ Class and Preferred Term for both the Double Masked and Open Label Periods. The summary of other adverse events in Double Masked Treatment Period and Open Label Treatment Period are independently summarized. For any other adverse events equal or over the threshold of 1% in open label but less than 1% in double masked, the AE will not be included in double masked (counted as 0). This is vice versa.

Additional Information

Director of R&D Quality Management

Santen Inc

Phone: 15106851794

Email: evelyn.chikere@santen.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place