Trial Outcomes & Findings for Study of Efficacy and Safety of SAF312 Eye Drops in Subjects With Post-operative Corneal Induced Chronic Pain (CICP) (NCT NCT04630158)

NCT ID: NCT04630158

Last Updated: 2024-10-09

Results Overview

The pain severity Visual Analogue Scale (VAS) was completed by the subject using an electronic diary. A vertical mark was placed on the horizontal scoring line (anchored with 'No Pain' on the left and 'Very Severe' pain on the right) to score the severity of ocular pain over the past 24 hours, with a range from 0 (min) to 100 (max). Higher scores indicate higher pain severity. A negative change from baseline is a positive outcome.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 153 participants
• Primary outcome timeframe: Baseline, Week 12
• Results posted on: 2024-10-09

Participant Flow

Participant milestones

Measure	SAF312 15 mg/mL Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5 mg/mL Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo Randomized to a 1:1:1 topical eye drops, twice daily
Overall Study STARTED	50	49	51
Overall Study COMPLETED	46	45	47
Overall Study NOT COMPLETED	4	4	4

Reasons for withdrawal

Measure	SAF312 15 mg/mL Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5 mg/mL Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo Randomized to a 1:1:1 topical eye drops, twice daily
Overall Study Adverse Event	1	1	1
Overall Study Physician Decision	0	2	0
Overall Study Protocol Violation	1	0	1
Overall Study Withdrawal by Subject	2	1	2

Baseline Characteristics

Study of Efficacy and Safety of SAF312 Eye Drops in Subjects With Post-operative Corneal Induced Chronic Pain (CICP)

Baseline characteristics by cohort

Measure	SAF312 15 mg/mL n=50 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5 mg/mL n=49 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=51 Participants Randomized to a 1:1:1 topical eye drops, twice daily	Total n=150 Participants Total of all reporting groups
Age, Continuous	61.0 years STANDARD_DEVIATION 15.56 • n=5 Participants	60.4 years STANDARD_DEVIATION 15.12 • n=7 Participants	56.8 years STANDARD_DEVIATION 17.15 • n=5 Participants	59.4 years STANDARD_DEVIATION 15.99 • n=4 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	34 Participants n=7 Participants	40 Participants n=5 Participants	109 Participants n=4 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	15 Participants n=7 Participants	11 Participants n=5 Participants	41 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	47 Participants n=5 Participants	49 Participants n=7 Participants	48 Participants n=5 Participants	144 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	7 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants	23 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	5 Participants n=7 Participants	4 Participants n=5 Participants	15 Participants n=4 Participants
Race (NIH/OMB) White	35 Participants n=5 Participants	37 Participants n=7 Participants	38 Participants n=5 Participants	110 Participants n=4 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 12

Population: Full Analysis Set - all treated patients

The pain severity Visual Analogue Scale (VAS) was completed by the subject using an electronic diary. A vertical mark was placed on the horizontal scoring line (anchored with 'No Pain' on the left and 'Very Severe' pain on the right) to score the severity of ocular pain over the past 24 hours, with a range from 0 (min) to 100 (max). Higher scores indicate higher pain severity. A negative change from baseline is a positive outcome.

Outcome measures

Measure	SAF312 15 mg/mL n=50 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5mg/mL n=49 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=51 Participants Randomized to a 1:1:1 topical eye drops, twice daily
Change From Baseline at Week 12 in Ocular Pain Severity Visual Analog Scale (VAS)	-23.7 Scores on a scale Standard Error 3.70	-21.7 Scores on a scale Standard Error 3.71	-25.3 Scores on a scale Standard Error 3.51

SECONDARY outcome

Timeframe: Baseline, Days 7 and 14

Population: Participants in the Full Analysis Set with an available value for the outcome measure at baseline and at each timepoint.

The pain severity Visual Analogue Scale (VAS) was completed by the subject using an electronic diary. A vertical mark was placed on the horizontal scoring line (anchored with 'No Pain' on the left and 'Very Severe' pain on the right) to score the severity of ocular pain over the past 24 hours, with a range from 0 (min) to 100 (max). Higher scores indicate higher pain severity. A negative change from baseline is a positive outcome.

Outcome measures

Measure	SAF312 15 mg/mL n=45 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5mg/mL n=44 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=44 Participants Randomized to a 1:1:1 topical eye drops, twice daily
Ocular Pain Severity Visual Analog Scale (VAS): Summary Statistics of Change From Baseline at Day 7 and Day 14 Day 7 (n=45,44,43)	-10.89 Scores on a scale Standard Deviation 18.373	-11.45 Scores on a scale Standard Deviation 20.661	-17.40 Scores on a scale Standard Deviation 21.558
Ocular Pain Severity Visual Analog Scale (VAS): Summary Statistics of Change From Baseline at Day 7 and Day 14 Day 14 (n=45,37,44)	-12.20 Scores on a scale Standard Deviation 21.484	-14.89 Scores on a scale Standard Deviation 25.790	-21.00 Scores on a scale Standard Deviation 21.624

SECONDARY outcome

Timeframe: Baseline, Weeks 1 to 12

Population: Participants in the Full Analysis Set with an available value for the outcome measure at baseline and at each timepoint.

The pain frequency Visual Analogue Scale (VAS) was completed by the subject using an electronic diary. A vertical mark was placed on the horizontal scoring line (anchored with 'No Pain' on the left and 'Very Frequent' pain on the right) to score the frequency of ocular pain over the past 24 hours, with a range from 0 (min) to 100 (max). Higher scores indicate higher pain frequency. A negative change from baseline is a positive outcome.

Outcome measures

Measure	SAF312 15 mg/mL n=50 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5mg/mL n=49 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=50 Participants Randomized to a 1:1:1 topical eye drops, twice daily
Ocular Pain Frequency Visual Analog Scale (VAS): Summary Statistics of Weekly Mean Change From Baseline to Week 12 Week 1	-10.22 Scores on a scale Standard Deviation 16.404	-9.96 Scores on a scale Standard Deviation 15.464	-12.45 Scores on a scale Standard Deviation 15.484
Ocular Pain Frequency Visual Analog Scale (VAS): Summary Statistics of Weekly Mean Change From Baseline to Week 12 Week 2 (n=49,48,50)	-14.38 Scores on a scale Standard Deviation 21.073	-12.68 Scores on a scale Standard Deviation 20.344	-18.80 Scores on a scale Standard Deviation 20.489
Ocular Pain Frequency Visual Analog Scale (VAS): Summary Statistics of Weekly Mean Change From Baseline to Week 12 Week 3 (n=49,47,49)	-17.35 Scores on a scale Standard Deviation 21.332	-14.75 Scores on a scale Standard Deviation 23.314	-22.45 Scores on a scale Standard Deviation 22.980
Ocular Pain Frequency Visual Analog Scale (VAS): Summary Statistics of Weekly Mean Change From Baseline to Week 12 Week 4 (n=49,46,48)	-19.06 Scores on a scale Standard Deviation 23.070	-12.75 Scores on a scale Standard Deviation 24.076	-24.07 Scores on a scale Standard Deviation 25.230
Ocular Pain Frequency Visual Analog Scale (VAS): Summary Statistics of Weekly Mean Change From Baseline to Week 12 Week 5 (n=49,46,48)	-20.34 Scores on a scale Standard Deviation 24.524	-14.31 Scores on a scale Standard Deviation 23.711	-26.18 Scores on a scale Standard Deviation 22.404
Ocular Pain Frequency Visual Analog Scale (VAS): Summary Statistics of Weekly Mean Change From Baseline to Week 12 Week 6 (n=48,47,48)	-19.84 Scores on a scale Standard Deviation 25.511	-15.60 Scores on a scale Standard Deviation 23.332	-23.88 Scores on a scale Standard Deviation 25.433
Ocular Pain Frequency Visual Analog Scale (VAS): Summary Statistics of Weekly Mean Change From Baseline to Week 12 Week 7 (n=47,47,48)	-22.84 Scores on a scale Standard Deviation 25.774	-17.60 Scores on a scale Standard Deviation 24.715	-25.09 Scores on a scale Standard Deviation 24.489
Ocular Pain Frequency Visual Analog Scale (VAS): Summary Statistics of Weekly Mean Change From Baseline to Week 12 Week 8 (n-47,45,48)	-23.25 Scores on a scale Standard Deviation 26.009	-17.40 Scores on a scale Standard Deviation 23.636	-24.69 Scores on a scale Standard Deviation 26.072
Ocular Pain Frequency Visual Analog Scale (VAS): Summary Statistics of Weekly Mean Change From Baseline to Week 12 Week 9 (n=46,44,48)	-24.30 Scores on a scale Standard Deviation 25.650	-18.01 Scores on a scale Standard Deviation 25.040	-24.92 Scores on a scale Standard Deviation 25.648
Ocular Pain Frequency Visual Analog Scale (VAS): Summary Statistics of Weekly Mean Change From Baseline to Week 12 Week 10 (n=46,44,47)	-25.16 Scores on a scale Standard Deviation 25.381	-18.44 Scores on a scale Standard Deviation 24.387	-25.72 Scores on a scale Standard Deviation 26.428
Ocular Pain Frequency Visual Analog Scale (VAS): Summary Statistics of Weekly Mean Change From Baseline to Week 12 Week 11 (n=46,45,47)	-26.62 Scores on a scale Standard Deviation 26.057	-21.68 Scores on a scale Standard Deviation 24.754	-25.66 Scores on a scale Standard Deviation 28.343
Ocular Pain Frequency Visual Analog Scale (VAS): Summary Statistics of Weekly Mean Change From Baseline to Week 12 Week 12 (n=46,43,47)	-26.24 Scores on a scale Standard Deviation 25.322	-20.38 Scores on a scale Standard Deviation 24.296	-26.98 Scores on a scale Standard Deviation 25.977

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12

Population: Participants in the Full Analysis Set with an available value for the outcome measure at baseline and at each timepoint.

Each question in the Ocular Pain Assessment Survey (OPAS) quality of life subscale was scored by the subject on a line marked from 0 (not at all) to 10 (completely) that described how much pain interfered with or affected a particular activity (max score= 10/question). A higher score suggests a higher impact by pain on a particular activity. A negative change from baseline is a positive outcome. There are 7 questions in total regarding Quality of Life. The average score of the 7 Quality of Life questions is reported (mean (SD)).

Outcome measures

Measure	SAF312 15 mg/mL n=48 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5mg/mL n=46 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=49 Participants Randomized to a 1:1:1 topical eye drops, twice daily
Ocular Pain Assessment Scale (OPAS) Subscale Quality of Life: Summary Statistics of Change From Baseline to Week 12 Week 2 (n=48,46,46)	-1.39 Scores on a scale Standard Deviation 1.839	-0.99 Scores on a scale Standard Deviation 2.027	-1.52 Scores on a scale Standard Deviation 1.704
Ocular Pain Assessment Scale (OPAS) Subscale Quality of Life: Summary Statistics of Change From Baseline to Week 12 Week 4 (n=46,46,49)	-1.68 Scores on a scale Standard Deviation 2.360	-1.39 Scores on a scale Standard Deviation 2.040	-2.00 Scores on a scale Standard Deviation 2.138
Ocular Pain Assessment Scale (OPAS) Subscale Quality of Life: Summary Statistics of Change From Baseline to Week 12 Week 8 (n=47,45,45)	-1.61 Scores on a scale Standard Deviation 2.428	-1.30 Scores on a scale Standard Deviation 2.103	-1.82 Scores on a scale Standard Deviation 1.805
Ocular Pain Assessment Scale (OPAS) Subscale Quality of Life: Summary Statistics of Change From Baseline to Week 12 Week 12 (n=45,45,45)	-2.20 Scores on a scale Standard Deviation 2.317	-1.79 Scores on a scale Standard Deviation 2.225	-2.06 Scores on a scale Standard Deviation 2.284

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12

Population: Participants in the Full Analysis Set with an available value for the outcome measure at baseline and at each timepoint.

Conjunctival redness in each of two regions (nasal and temporal) was graded on a scale from 0 to 5 using the McMonnies conjunctival redness photographic scale (max score=5/region). Higher scores suggest higher degrees of redness (worsening). A negative change from baseline is a positive outcome.

Outcome measures

Measure	SAF312 15 mg/mL n=47 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5mg/mL n=45 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=46 Participants Randomized to a 1:1:1 topical eye drops, twice daily
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Nasal (Oculus Dexter (OD) = Right Eye) Week 2 (n=47,44,43)	-0.1 Scores on a scale Standard Deviation 0.75	-0.0 Scores on a scale Standard Deviation 0.43	-0.1 Scores on a scale Standard Deviation 0.65
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Nasal (Oculus Dexter (OD) = Right Eye) Week 4 (n=44,45,46)	-0.2 Scores on a scale Standard Deviation 0.77	-0.0 Scores on a scale Standard Deviation 0.67	0.0 Scores on a scale Standard Deviation 0.52
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Nasal (Oculus Dexter (OD) = Right Eye) Week 8 (n=45,43,42)	-0.2 Scores on a scale Standard Deviation 0.72	-0.1 Scores on a scale Standard Deviation 0.68	-0.2 Scores on a scale Standard Deviation 0.62
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Nasal (Oculus Dexter (OD) = Right Eye) Week 12 (n=44,43,44)	-0.2 Scores on a scale Standard Deviation 0.70	-0.0 Scores on a scale Standard Deviation 0.75	-0.1 Scores on a scale Standard Deviation 0.76

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12

Population: Participants in the Full Analysis Set with an available value for the outcome measure at baseline and at each timepoint.

Conjunctival redness in each of two regions (nasal and temporal) was graded on a scale from 0 to 5 using the McMonnies conjunctival redness photographic scale (max score=5/region). Higher scores suggest higher degrees of redness (worsening). A negative change from baseline is a positive outcome.

Outcome measures

Measure	SAF312 15 mg/mL n=47 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5mg/mL n=45 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=46 Participants Randomized to a 1:1:1 topical eye drops, twice daily
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Nasal (Oculus Sinister (OS) = Left Eye) Week 2 (n=47,44,43)	-0.2 Scores on a scale Standard Deviation 0.67	-0.1 Scores on a scale Standard Deviation 0.45	-0.2 Scores on a scale Standard Deviation 0.61
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Nasal (Oculus Sinister (OS) = Left Eye) Week 4 (N=44,45,46)	-0.3 Scores on a scale Standard Deviation 0.78	0.0 Scores on a scale Standard Deviation 0.67	-0.1 Scores on a scale Standard Deviation 0.41
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Nasal (Oculus Sinister (OS) = Left Eye) Week 8 (n=45,43,42)	-0.2 Scores on a scale Standard Deviation 0.70	-0.2 Scores on a scale Standard Deviation 0.73	-0.2 Scores on a scale Standard Deviation 0.61
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Nasal (Oculus Sinister (OS) = Left Eye) Week 12 (n=44,43,44)	-0.2 Scores on a scale Standard Deviation 0.68	-0.1 Scores on a scale Standard Deviation 0.59	-0.2 Scores on a scale Standard Deviation 0.83

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12

Population: Participants in the Full Analysis Set with an available value for the outcome measure at baseline and at each timepoint.

The pain severity Visual Analogue Scale (VAS) was completed by the subject using an electronic diary. A vertical mark was placed on the horizontal scoring line (anchored with 'No Pain' on the left and 'Very Severe' pain on the right) to score the severity of ocular pain over the past 24 hours, with a range from 0 (min) to 100 (max). Higher scores indicate higher pain severity. A negative change from baseline is a positive outcome. A negative change from baseline is a positive outcome.

Outcome measures

Measure	SAF312 15 mg/mL n=47 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5mg/mL n=45 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=46 Participants Randomized to a 1:1:1 topical eye drops, twice daily
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Temporal (Oculus Dexter (OD) = Right Eye) Week 4 (n=44,45,46)	-0.3 Scores on a scale Standard Deviation 0.83	0.0 Scores on a scale Standard Deviation 0.71	-0.1 Scores on a scale Standard Deviation 0.57
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Temporal (Oculus Dexter (OD) = Right Eye) Week 8 (n=45,43,42)	-0.2 Scores on a scale Standard Deviation 0.84	-0.1 Scores on a scale Standard Deviation 0.80	-0.2 Scores on a scale Standard Deviation 0.76
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Temporal (Oculus Dexter (OD) = Right Eye) Week 12 (n=44,43,44)	-0.3 Scores on a scale Standard Deviation 0.78	-0.1 Scores on a scale Standard Deviation 0.73	-0.3 Scores on a scale Standard Deviation 0.99
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Temporal (Oculus Dexter (OD) = Right Eye) Week 2 (n=47,44,43)	-0.2 Scores on a scale Standard Deviation 0.72	0.1 Scores on a scale Standard Deviation 0.55	-0.1 Scores on a scale Standard Deviation 0.68

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12

Population: Participants in the Full Analysis Set with an available value for the outcome measure at baseline and at each timepoint.

Conjunctival redness in each of two regions (nasal and temporal) was graded on a scale from 0 to 5 using the McMonnies conjunctival redness photographic scale (max score=5/region). Higher scores suggest higher degrees of redness (worsening). A negative change from baseline is a positive outcome.

Outcome measures

Measure	SAF312 15 mg/mL n=47 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5mg/mL n=45 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=46 Participants Randomized to a 1:1:1 topical eye drops, twice daily
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Temporal (Oculus Sinister (OS) = Left Eye) Week 8 (n=45,43,42)	-0.2 Scores on a scale Standard Deviation 0.67	-0.1 Scores on a scale Standard Deviation 0.70	-0.1 Scores on a scale Standard Deviation 0.69
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Temporal (Oculus Sinister (OS) = Left Eye) Week 4 (n=44,45,46)	-0.4 Scores on a scale Standard Deviation 0.81	0.1 Scores on a scale Standard Deviation 0.61	0.1 Scores on a scale Standard Deviation 0.57
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Temporal (Oculus Sinister (OS) = Left Eye) Week 12 (n=44,43,44)	-0.3 Scores on a scale Standard Deviation 0.71	-0.1 Scores on a scale Standard Deviation 0.63	-0.2 Scores on a scale Standard Deviation 0.90
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Redness - Temporal (Oculus Sinister (OS) = Left Eye) Week 2 (n=47,44,43)	-0.2 Scores on a scale Standard Deviation 0.74	0.0 Scores on a scale Standard Deviation 0.53	-0.1 Scores on a scale Standard Deviation 0.72

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12

Population: Participants in the Full Analysis Set with an available value for the outcome measure at baseline and at each timepoint.

The degree of lissamine conjunctival staining in two regions (temporal and nasal) was graded on a scale from 0 to 4 (max score = 8/eye). Higher scores suggest higher degrees of corneal staining (worsening). A negative change from baseline is a positive outcome.

Outcome measures

Measure	SAF312 15 mg/mL n=47 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5mg/mL n=45 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=46 Participants Randomized to a 1:1:1 topical eye drops, twice daily
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Staining (Oculus Dexter (OD) = Right Eye) Week 2 (n=47,44,43)	0.1 Scores on a scale Standard Deviation 0.99	-0.0 Scores on a scale Standard Deviation 1.23	-0.1 Scores on a scale Standard Deviation 1.06
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Staining (Oculus Dexter (OD) = Right Eye) Week 4 (n=44,45,46)	0.0 Scores on a scale Standard Deviation 1.27	0.2 Scores on a scale Standard Deviation 1.62	-0.2 Scores on a scale Standard Deviation 1.23
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Staining (Oculus Dexter (OD) = Right Eye) Week 8 (n=45,42,42)	-0.2 Scores on a scale Standard Deviation 1.00	0.0 Scores on a scale Standard Deviation 1.06	0.3 Scores on a scale Standard Deviation 1.27
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Staining (Oculus Dexter (OD) = Right Eye) Week 12 (n=44,43,44)	0.1 Scores on a scale Standard Deviation 1.39	-0.1 Scores on a scale Standard Deviation 1.24	0.0 Scores on a scale Standard Deviation 1.54

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12

Population: Participants in the Full Analysis Set with an available value for the outcome measure at baseline and at each timepoint.

The degree of lissamine conjunctival staining in two regions (temporal and nasal) was graded on a scale from 0 to 4 (max score = 8/eye). Higher scores suggest higher degrees of corneal staining (worsening). A negative change from baseline is a positive outcome.

Outcome measures

Measure	SAF312 15 mg/mL n=47 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5mg/mL n=45 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=46 Participants Randomized to a 1:1:1 topical eye drops, twice daily
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Staining (Oculus Sinister (OS) = Left Eye) Week 2 (n=47,44,43)	0.0 Scores on a scale Standard Deviation 0.99	-0.1 Scores on a scale Standard Deviation 1.51	-0.2 Scores on a scale Standard Deviation 1.41
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Staining (Oculus Sinister (OS) = Left Eye) Week 4 (n=44,45,46)	-0.1 Scores on a scale Standard Deviation 1.20	0.1 Scores on a scale Standard Deviation 1.47	-0.1 Scores on a scale Standard Deviation 1.41
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Staining (Oculus Sinister (OS) = Left Eye) Week 8 (n=45,42,42)	-0.2 Scores on a scale Standard Deviation 1.01	-0.3 Scores on a scale Standard Deviation 1.32	0.1 Scores on a scale Standard Deviation 1.46
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Conjunctival Staining (Oculus Sinister (OS) = Left Eye) Week 12 (n=44,43,44)	-0.1 Scores on a scale Standard Deviation 1.25	-0.1 Scores on a scale Standard Deviation 1.16	-0.1 Scores on a scale Standard Deviation 1.25

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12

Population: Participants in the Full Analysis Set with an available value for the outcome measure at baseline and at each timepoint.

The degree of corneal fluorescein staining in each of five regions (superior, inferior, nasal, temporal, and central) was graded on a scale from 0 to 4 (max score=20/eye). Higher scores suggest higher degrees of corneal staining (worsening). A negative change from baseline is a positive outcome.

Outcome measures

Measure	SAF312 15 mg/mL n=49 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5mg/mL n=47 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=49 Participants Randomized to a 1:1:1 topical eye drops, twice daily
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Corneal Staining (Oculus Dexter (OD) = Right Eye) Week 12 (n=46,45,47)	-0.7 Scores on a scale Standard Deviation 3.10	-0.1 Scores on a scale Standard Deviation 1.95	-1.5 Scores on a scale Standard Deviation 2.78
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Corneal Staining (Oculus Dexter (OD) = Right Eye) Week 8 (n=47,45,45)	-0.9 Scores on a scale Standard Deviation 2.93	-0.6 Scores on a scale Standard Deviation 2.09	-0.8 Scores on a scale Standard Deviation 2.40
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Corneal Staining (Oculus Dexter (OD) = Right Eye) Week 2 (n=49,46,46)	-0.6 Scores on a scale Standard Deviation 2.02	-0.7 Scores on a scale Standard Deviation 1.73	-0.7 Scores on a scale Standard Deviation 2.76
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Corneal Staining (Oculus Dexter (OD) = Right Eye) Week 4 (n=46,47,49)	-0.8 Scores on a scale Standard Deviation 2.84	-0.1 Scores on a scale Standard Deviation 2.47	-0.9 Scores on a scale Standard Deviation 2.32

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12

Population: Participants in the Full Analysis Set with an available value for the outcome measure at baseline and at each timepoint.

The degree of corneal fluorescein staining in each of five regions (superior, inferior, nasal, temporal, and central) was graded on a scale from 0 to 4 (max score=20/eye). Higher scores suggest higher degrees of corneal staining (worsening). A negative change from baseline is a positive outcome.

Outcome measures

Measure	SAF312 15 mg/mL n=49 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5mg/mL n=47 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=49 Participants Randomized to a 1:1:1 topical eye drops, twice daily
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Corneal Staining (Oculus Sinister (OS) = Left Eye) Week 8 (n=47,45,45)	-1.2 Scores on a scale Standard Deviation 3.51	-0.8 Scores on a scale Standard Deviation 2.46	-0.9 Scores on a scale Standard Deviation 2.85
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Corneal Staining (Oculus Sinister (OS) = Left Eye) Week 12 (n=46,45,47)	-0.9 Scores on a scale Standard Deviation 3.33	-0.5 Scores on a scale Standard Deviation 2.19	-1.5 Scores on a scale Standard Deviation 3.14
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Corneal Staining (Oculus Sinister (OS) = Left Eye) Week 2 (n=49,46,46)	-0.5 Scores on a scale Standard Deviation 2.48	-0.7 Scores on a scale Standard Deviation 2.55	-1.0 Scores on a scale Standard Deviation 2.82
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week - Corneal Staining (Oculus Sinister (OS) = Left Eye) Week 4 (n=46,47,49)	-0.7 Scores on a scale Standard Deviation 2.67	-0.6 Scores on a scale Standard Deviation 2.62	-0.6 Scores on a scale Standard Deviation 2.51

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12

Population: Participants in the Full Analysis Set with an available value for the outcome measure at baseline and at each timepoint.

The Schirmer's test was performed without anesthetic. Tear secretion was measured in millimeters based on the length of strip wetted by tears (max score =35 mm/eye). Lower values indicate lower relative amounts of tear secretion (worsening). A negative change from baseline is a positive outcome.

Outcome measures

Measure	SAF312 15 mg/mL n=49 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5mg/mL n=47 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=49 Participants Randomized to a 1:1:1 topical eye drops, twice daily
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week of Tear Production - Schirmer Test (mm) (Oculus Dexter (OD) = Right Eye) Week 4 (n=46,47,49)	-0.3 mm Standard Deviation 7.45	-1.4 mm Standard Deviation 7.85	0.1 mm Standard Deviation 7.40
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week of Tear Production - Schirmer Test (mm) (Oculus Dexter (OD) = Right Eye) Week 2 (n=49,45,46)	-1.1 mm Standard Deviation 8.38	-0.3 mm Standard Deviation 8.62	-0.3 mm Standard Deviation 7.67
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week of Tear Production - Schirmer Test (mm) (Oculus Dexter (OD) = Right Eye) Week 8 (n=47,43,45)	0.0 mm Standard Deviation 8.04	-1.7 mm Standard Deviation 9.89	-1.4 mm Standard Deviation 8.45
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week of Tear Production - Schirmer Test (mm) (Oculus Dexter (OD) = Right Eye) Week 12 (n=46,45,47)	-0.7 mm Standard Deviation 7.79	-0.9 mm Standard Deviation 7.02	0.9 mm Standard Deviation 7.77

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, 8, 12

Population: Participants in the Full Analysis Set with an available value for the outcome measure at baseline and at each timepoint.

The Schirmer's test was performed without anesthetic. Tear secretion was measured in millimeters based on the length of strip wetted by tears (max score =35 mm/eye). Lower values indicate lower relative amounts of tear secretion (worsening). A negative change from baseline is a positive outcome.

Outcome measures

Measure	SAF312 15 mg/mL n=49 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5mg/mL n=47 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=49 Participants Randomized to a 1:1:1 topical eye drops, twice daily
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week of Tear Production - Schirmer Test (mm) (Oculus Sinister (OS) = Left Eye) Week 2 (n=49,45,46)	-0.7 mm Standard Deviation 8.98	-1.5 mm Standard Deviation 7.81	0.6 mm Standard Deviation 4.82
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week of Tear Production - Schirmer Test (mm) (Oculus Sinister (OS) = Left Eye) Week 4 (n=46,47,49)	0.7 mm Standard Deviation 7.52	-2.1 mm Standard Deviation 7.78	1.4 mm Standard Deviation 7.59
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week of Tear Production - Schirmer Test (mm) (Oculus Sinister (OS) = Left Eye) Week 8 (n=47,43,45)	0.2 mm Standard Deviation 8.30	-1.1 mm Standard Deviation 8.71	-0.7 mm Standard Deviation 6.92
Ocular Surface Parameters: Summary Statistics of Change From Baseline by Week of Tear Production - Schirmer Test (mm) (Oculus Sinister (OS) = Left Eye) Week 12 (n=46,45,47)	0.1 mm Standard Deviation 9.51	-2.2 mm Standard Deviation 8.60	1.1 mm Standard Deviation 7.88

SECONDARY outcome

Timeframe: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).

Population: Safety set

An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.

Outcome measures

Measure	SAF312 15 mg/mL n=50 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5mg/mL n=49 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=51 Participants Randomized to a 1:1:1 topical eye drops, twice daily
Number of Participants With Treatment Emergent Adverse Events Any adverse events	21 Participants	12 Participants	18 Participants
Number of Participants With Treatment Emergent Adverse Events -Any ocular adverse events	11 Participants	10 Participants	10 Participants
Number of Participants With Treatment Emergent Adverse Events -Any non-ocular adverse events	13 Participants	4 Participants	13 Participants
Number of Participants With Treatment Emergent Adverse Events Any serious adverse events	0 Participants	0 Participants	1 Participants
Number of Participants With Treatment Emergent Adverse Events -Any ocular serious adverse events	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events -Any non-ocular serious adverse events	0 Participants	0 Participants	1 Participants
Number of Participants With Treatment Emergent Adverse Events Any study drug related adverse events	5 Participants	5 Participants	2 Participants
Number of Participants With Treatment Emergent Adverse Events -Any study drug related ocular adverse events	5 Participants	5 Participants	2 Participants
Number of Participants With Treatment Emergent Adverse Events -Any study drug related non-ocular adverse events	0 Participants	1 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events Any adverse events leading to study drug discontinuation	1 Participants	1 Participants	1 Participants
Number of Participants With Treatment Emergent Adverse Events -Any ocular adverse events leading to study drug discontinuation	0 Participants	1 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events -Any non-ocular adverse events leading to study drug discontinuation	1 Participants	1 Participants	1 Participants
Number of Participants With Treatment Emergent Adverse Events Any study drug related serious adverse events	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events -Any study drug related ocular serious adverse events	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events -Any study drug related non-ocular serious adverse events	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment Emergent Adverse Events Death	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).

Population: Safety set

An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.

MedDRA Version 26.0 was used for the reporting of adverse events.

Outcome measures

Measure	SAF312 15 mg/mL n=50 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5mg/mL n=49 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=51 Participants Randomized to a 1:1:1 topical eye drops, twice daily
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) Number of subjects with at least one event	11 Participants	10 Participants	10 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) SOC: Eye disorders	10 Participants	8 Participants	10 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Eye pain	3 Participants	0 Participants	2 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Dry eye	2 Participants	2 Participants	0 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Eye pruritus	2 Participants	1 Participants	0 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Dry age-related macular degeneration	1 Participants	0 Participants	0 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Eye discharge	1 Participants	2 Participants	1 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Eye irritation	1 Participants	1 Participants	1 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Vision blurred	1 Participants	1 Participants	1 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Instillation site pruritus	0 Participants	1 Participants	0 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Vitreous detachment	1 Participants	0 Participants	0 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Blepharitis	0 Participants	0 Participants	1 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Chalazion	0 Participants	0 Participants	2 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Conjunctival papillae	0 Participants	1 Participants	0 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Corneal oedema	0 Participants	0 Participants	1 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Erythema of eyelid	0 Participants	3 Participants	0 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Lacrimation increased	0 Participants	1 Participants	0 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Ocular hyperaemia	0 Participants	2 Participants	1 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Optic nerve cupping	0 Participants	0 Participants	1 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Swelling of eyelid	0 Participants	1 Participants	0 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) SOC: General disorders and administration site conditions	0 Participants	4 Participants	0 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Instillation site irritation	0 Participants	2 Participants	0 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Therapy responder	0 Participants	1 Participants	0 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) SOC: Immune system disorders	0 Participants	1 Participants	0 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Drug hypersensitivity	0 Participants	1 Participants	0 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) SOC: Infections and infestations	2 Participants	0 Participants	0 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Hordeolum	2 Participants	0 Participants	0 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) SOC: Injury, poisoning and procedural complications	0 Participants	0 Participants	1 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Corneal abrasion	0 Participants	0 Participants	1 Participants
Ocular Treatment Emergent Adverse Events, by Primary System Organ Class (SOC) and Preferred Term (PT) -Foreign body in eye	0 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).

Population: Safety set

An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.

Outcome measures

Measure	SAF312 15 mg/mL n=50 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5mg/mL n=49 Participants Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=51 Participants Randomized to a 1:1:1 topical eye drops, twice daily
Summary of Non-ocular Treatment Emergent Adverse Events	13 Participants	4 Participants	13 Participants

Adverse Events

SAF312 15 mg/mL

Serious events: 0 serious events

Other events: 21 other events

Deaths: 0 deaths

SAF312 5 mg/mL

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

SAF312 Placebo

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Total

Serious events: 1 serious events

Other events: 51 other events

Deaths: 0 deaths

Serious adverse events

Measure	SAF312 15 mg/mL n=50 participants at risk Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5 mg/mL n=49 participants at risk Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=51 participants at risk Randomized to a 1:1:1 topical eye drops, twice daily	Total n=150 participants at risk Total
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).

Other adverse events

Measure	SAF312 15 mg/mL n=50 participants at risk Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 5 mg/mL n=49 participants at risk Randomized to a 1:1:1 topical eye drops, twice daily	SAF312 Placebo n=51 participants at risk Randomized to a 1:1:1 topical eye drops, twice daily	Total n=150 participants at risk Total
Eye disorders Blepharitis	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Eye disorders Chalazion	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	3.9% 2/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	1.3% 2/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Eye disorders Conjunctival papillae	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Eye disorders Corneal oedema	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Eye disorders Dry age-related macular degeneration	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Eye disorders Dry eye	4.0% 2/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	4.1% 2/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.7% 4/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Eye disorders Erythema of eyelid	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	6.1% 3/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 3/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Eye disorders Eye discharge	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	4.1% 2/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.7% 4/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Eye disorders Eye irritation	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 3/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Eye disorders Eye pain	6.0% 3/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	3.9% 2/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	3.3% 5/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Eye disorders Eye pruritus	4.0% 2/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 3/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Eye disorders Lacrimation increased	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Eye disorders Ocular hyperaemia	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	4.1% 2/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 3/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Eye disorders Optic nerve cupping	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Eye disorders Swelling of eyelid	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Eye disorders Vision blurred	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 3/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Eye disorders Vitreous detachment	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Gastrointestinal disorders Nausea	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Gastrointestinal disorders Vomiting	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
General disorders Instillation site irritation	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	4.1% 2/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	1.3% 2/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
General disorders Instillation site pruritus	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
General disorders Medical device site irritation	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
General disorders Non-cardiac chest pain	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
General disorders Therapy responder	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Immune system disorders Drug hypersensitivity	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Infections and infestations COVID-19	4.0% 2/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	5.9% 3/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	4.0% 6/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Infections and infestations Ear infection	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Infections and infestations Herpes virus infection	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Infections and infestations Herpes zoster	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Infections and infestations Hordeolum	4.0% 2/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	1.3% 2/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Infections and infestations Laryngitis	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Infections and infestations Nasopharyngitis	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	3.9% 2/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	1.3% 2/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Infections and infestations Pharyngitis streptococcal	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Infections and infestations Sinusitis	6.0% 3/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 3/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Infections and infestations Upper respiratory tract infection	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Infections and infestations Urinary tract infection	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Injury, poisoning and procedural complications Buttock injury	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Injury, poisoning and procedural complications Corneal abrasion	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Injury, poisoning and procedural complications Fall	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Injury, poisoning and procedural complications Foreign body in eye	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Injury, poisoning and procedural complications Joint injury	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Injury, poisoning and procedural complications Skin laceration	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Musculoskeletal and connective tissue disorders Arthralgia	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Musculoskeletal and connective tissue disorders Exostosis	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Sarcoma	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Nervous system disorders Dizziness	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	1.3% 2/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Nervous system disorders Headache	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Skin and subcutaneous tissue disorders Diabetic bullosis	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	1.3% 2/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Skin and subcutaneous tissue disorders Rash	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Vascular disorders Hot flush	0.00% 0/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	2.0% 1/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).
Vascular disorders Hypertension	2.0% 1/50 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/49 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.00% 0/51 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).	0.67% 1/150 • Adverse events are reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum timeframe of 119 days (approximately 4 months).

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: + 1 862 778 8300

Email: Novartis.email@Novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER