Trial Outcomes & Findings for Ranibizumab Intravitreal Injections Versus Sham Control in Patients With Branch Retinal Vein Occlusion (BRVO) (NCT NCT01976338)

NCT ID: NCT01976338

Last Updated: 2017-05-08

Results Overview

Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters. Mean Visual Acuity was averaged over all monthly assessments from month 1 to month 6 and compared to Baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

283 participants

Primary outcome timeframe

Baseline to Month 1 through Month 6

Results posted on

2017-05-08

Participant Flow

This study consisted of the following three periods (Screening period: Day -14 to Day -1; treatment period: Day 1 to Month 11; post-treatment Follow-Up period: Month 11 to Month 12). At Baseline (Visit 2, Day 1), eligible patients were randomized in a 2:1 ratio into respective treatment arms

Participant milestones

Participant milestones
Measure	Ranibizumab 0.5 mg PRN Intravitreal injection	Sham Injection As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
Overall Study STARTED	190	93
Overall Study Completed 6 Months	185	91
Overall Study Discontinued Study Prior to 6 Months	5	2
Overall Study COMPLETED	177	89
Overall Study NOT COMPLETED	13	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Ranibizumab 0.5 mg PRN Intravitreal injection	Sham Injection As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
Overall Study Physician Decision	0	1
Overall Study Lost to Follow-up	3	0
Overall Study Withdrawal by Subject	5	2
Overall Study Adverse Event	5	1

Baseline Characteristics

Ranibizumab Intravitreal Injections Versus Sham Control in Patients With Branch Retinal Vein Occlusion (BRVO)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ranibizumab 0.5 mg n=190 Participants PRN Intravitreal injection	Sham Injection n=93 Participants As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection	Total n=283 Participants Total of all reporting groups
Age, Continuous	57.0 Years STANDARD_DEVIATION 10.14 • n=5 Participants	56.8 Years STANDARD_DEVIATION 10.03 • n=7 Participants	56.9 Years STANDARD_DEVIATION 10.09 • n=5 Participants
Sex: Female, Male Female	101 Participants n=5 Participants	38 Participants n=7 Participants	139 Participants n=5 Participants
Sex: Female, Male Male	89 Participants n=5 Participants	55 Participants n=7 Participants	144 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Month 1 through Month 6

Population: The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment group they had been assigned to at randomization. Mean value interpolation and last observation carried forward (MV-LOCF)

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg n=189 Participants PRN Intravitreal injection	Sham Injection n=93 Participants As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
Average Change in Best Corrected Visual Acuity (BCVA) From Baseline to Month 1 Through Month 6	12.5 Letters Standard Deviation 8.34	5.0 Letters Standard Deviation 9.18

SECONDARY outcome

Timeframe: Baseline to Month 1 through Month 12

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg n=189 Participants PRN Intravitreal injection	Sham Injection n=93 Participants As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
Average Change of Best Corrected Visual Acuity (BCVA) in Patients From Baseline to Month 1 Through Month 12	14.0 Letters Standard Deviation 8.99	7.7 Letters Standard Deviation 9.41

SECONDARY outcome

Timeframe: Month 1 through Month 12

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg n=189 Participants PRN Intravitreal injection	Sham Injection n=93 Participants As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
Best Corrected Visual Acuity (BCVA) Change Over Time Month 1	9.5 Letters Standard Deviation 8.26	1.7 Letters Standard Deviation 8.70
Best Corrected Visual Acuity (BCVA) Change Over Time Month 2	11.7 Letters Standard Deviation 8.39	3.7 Letters Standard Deviation 8.81
Best Corrected Visual Acuity (BCVA) Change Over Time Month 3	12.9 Letters Standard Deviation 8.81	5.1 Letters Standard Deviation 10.10
Best Corrected Visual Acuity (BCVA) Change Over Time Month 4	13.4 Letters Standard Deviation 9.72	6.0 Letters Standard Deviation 10.44
Best Corrected Visual Acuity (BCVA) Change Over Time Month 5	13.6 Letters Standard Deviation 10.24	6.5 Letters Standard Deviation 11.53
Best Corrected Visual Acuity (BCVA) Change Over Time Month 6	14.0 Letters Standard Deviation 10.75	7.0 Letters Standard Deviation 12.75
Best Corrected Visual Acuity (BCVA) Change Over Time Month 7	14.7 Letters Standard Deviation 10.62	8.5 Letters Standard Deviation 10.97
Best Corrected Visual Acuity (BCVA) Change Over Time Month 8	14.9 Letters Standard Deviation 10.52	10.4 Letters Standard Deviation 10.97
Best Corrected Visual Acuity (BCVA) Change Over Time Month 9	14.8 Letters Standard Deviation 10.43	10.3 Letters Standard Deviation 10.78
Best Corrected Visual Acuity (BCVA) Change Over Time Month 10	15.8 Letters Standard Deviation 10.67	11.2 Letters Standard Deviation 11.12
Best Corrected Visual Acuity (BCVA) Change Over Time Month 11	15.8 Letters Standard Deviation 10.42	11.1 Letters Standard Deviation 10.48
Best Corrected Visual Acuity (BCVA) Change Over Time Month 12	16.4 Letters Standard Deviation 10.95	11.3 Letters Standard Deviation 11.11

SECONDARY outcome

Timeframe: Baseline to month 12

Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg n=190 Participants PRN Intravitreal injection	Sham Injection n=93 Participants As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 12 Gain of >=30 letters	24 Participants	5 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 1 Gain of >=5 letters	139 Participants	33 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 1 Gain of >=10 letters	86 Participants	12 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 1 Gain of >=15 letters	43 Participants	3 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 1 Gain of >=30 letters	2 Participants	0 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 2 Gain of >=5 letters	156 Participants	44 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 2 Gain of >=10 letters	113 Participants	21 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 2 Gain of >=15 letters	72 Participants	6 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 2 Gain of >=30 letters	6 Participants	2 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 3 Gain of >=5 letters	162 Participants	49 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 3 Gain of >=10 letters	116 Participants	29 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 3 Gain of >=15 letters	76 Participants	16 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 3 Gain of >=30 letters	8 Participants	0 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 4 Gain of >=5 letters	159 Participants	55 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 4 Gain of >=10 letters	122 Participants	32 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 4 Gain of >=15 letters	83 Participants	16 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 4 Gain of >=30 letters	11 Participants	2 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 5 Gain of >=5 letters	159 Participants	60 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 5 Gain of >=10 letters	127 Participants	40 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 5 Gain of >=15 letters	83 Participants	19 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 5 Gain of >=30 letters	15 Participants	2 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 6 Gain of >=5 letters	163 Participants	58 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 6 Gain of >=10 letters	129 Participants	47 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 6 Gain of >=15 letters	88 Participants	25 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 6 Gain of >=30 letters	16 Participants	3 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 7 Gain of >=5 letters	162 Participants	63 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 7 Gain of >=10 letters	135 Participants	49 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 7 Gain of >=15 letters	93 Participants	28 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 7 Gain of >=30 letters	16 Participants	3 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 8 Gain of >=5 letters	168 Participants	66 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 8 Gain of >=150 letters	130 Participants	52 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 8 Gain of >=15 letters	94 Participants	33 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 8 Gain of >=30 letters	17 Participants	4 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 9 Gain of >=5 letters	163 Participants	67 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 9 Gain of >=10 letters	139 Participants	52 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 9 Gain of >=15 letters	90 Participants	32 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 9 Gain of >=30 letters	17 Participants	4 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 10 Gain of >=5 letters	169 Participants	68 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 10 Gain of >=10 letters	143 Participants	53 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 10 Gain of >=15 letters	97 Participants	37 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 10 Gain of >=30 letters	22 Participants	7 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 11 Gain of >=5 letters	172 Participants	67 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 11 Gain of >=10 letters	141 Participants	56 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 11 Gain of >=15 letters	103 Participants	36 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 11 Gain of >=30 letters	19 Participants	4 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 12 Gain of >=5 letters	171 Participants	72 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 12 Gain of >=10 letters	142 Participants	56 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 12 Gain of >=15 letters	105 Participants	36 Participants

SECONDARY outcome

Timeframe: Baseline to 12 months

Visual acuity (VA) was assessed at every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. This outcome measure describes for each post-baseline month whether or not a patient lost less than 15 letters of VA as compared with baseline.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg n=190 Participants PRN Intravitreal injection	Sham Injection n=93 Participants As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of 15 Letters in the Study Eye Month 1, Loss of < 15 letters	188 Participants	89 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of 15 Letters in the Study Eye Month 2, Loss of < 15 letters	189 Participants	90 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of 15 Letters in the Study Eye Month 3, Loss of < 15 letters	189 Participants	88 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of 15 Letters in the Study Eye Month 4, Loss of < 15 letters	189 Participants	88 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of 15 Letters in the Study Eye Month 5, Loss of < 15 letters	189 Participants	88 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of 15 Letters in the Study Eye Month 6, Loss of < 15 letters	188 Participants	89 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of 15 Letters in the Study Eye Month 7, Loss of < 15 letters	188 Participants	91 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of 15 Letters in the Study Eye Month 8, Loss of < 15 letters	188 Participants	92 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of 15 Letters in the Study Eye Month 9, Loss of < 15 letters	187 Participants	93 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of 15 Letters in the Study Eye Month 10, Loss of < 15 letters	188 Participants	92 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of 15 Letters in the Study Eye Month 11, Loss of < 15 letters	187 Participants	93 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of 15 Letters in the Study Eye Month 12, Loss of < 15 letters	187 Participants	91 Participants

SECONDARY outcome

Timeframe: Month 1 to month 12

OCT (optical coherence tomography) was used to assess CSFT (Central Sub-Field Thickness) representing the average retinal thickness of the circular area within 1 mm diameter around the foveal center

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg n=188 Participants PRN Intravitreal injection	Sham Injection n=93 Participants As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
Change in Central-Sub-Field- Thickness (CSFT) Over Time Month 1	-261.1 µm Standard Deviation 171.95	-42.4 µm Standard Deviation 171.88
Change in Central-Sub-Field- Thickness (CSFT) Over Time Month 2	-274.8 µm Standard Deviation 174.17	-93.1 µm Standard Deviation 187.14
Change in Central-Sub-Field- Thickness (CSFT) Over Time Month 3	-282.2 µm Standard Deviation 175.86	-155.3 µm Standard Deviation 209.37
Change in Central-Sub-Field- Thickness (CSFT) Over Time Month 4	-254.7 µm Standard Deviation 183.87	-193.2 µm Standard Deviation 221.58
Change in Central-Sub-Field- Thickness (CSFT) Over Time Month 5	-258.6 µm Standard Deviation 180.57	-203.2 µm Standard Deviation 218.02
Change in Central-Sub-Field- Thickness (CSFT) Over Time Month 6	-264.1 µm Standard Deviation 168.64	-206.6 µm Standard Deviation 221.85
Change in Central-Sub-Field- Thickness (CSFT) Over Time Month 7	-265.4 µm Standard Deviation 179.06	-289.8 µm Standard Deviation 228.03
Change in Central-Sub-Field- Thickness (CSFT) Over Time Month 8	-263.8 µm Standard Deviation 179.38	-286.1 µm Standard Deviation 236.75
Change in Central-Sub-Field- Thickness (CSFT) Over Time Month 9	-266.7 µm Standard Deviation 182.60	-287.9 µm Standard Deviation 237.61
Change in Central-Sub-Field- Thickness (CSFT) Over Time Month 10	-268.4 µm Standard Deviation 173.71	-282.9 µm Standard Deviation 239.98
Change in Central-Sub-Field- Thickness (CSFT) Over Time Month 11	-270.6 µm Standard Deviation 184.34	-290.3 µm Standard Deviation 227.47
Change in Central-Sub-Field- Thickness (CSFT) Over Time Month 12	-273.4 µm Standard Deviation 184.33	-282.9 µm Standard Deviation 233.69

SECONDARY outcome

Timeframe: month 3, 6 and 12

Fluorescein leakage area was assessed using Fluorescein angiography (FA) in conjunction with 7-field color fundus photography (CF) at Screening, Month 3, Month 6 and End of Study visit for both eyes

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg n=186 Participants PRN Intravitreal injection	Sham Injection n=90 Participants As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
Change in Total Area of Fluorescein Leakage (Center Subfield) From Baseline Over Time Month 3	-0.400 mm^2 Standard Deviation 0.3576	-0.026 mm^2 Standard Deviation 0.3387
Change in Total Area of Fluorescein Leakage (Center Subfield) From Baseline Over Time Month 6	-0.356 mm^2 Standard Deviation 0.3983	-0.055 mm^2 Standard Deviation 0.4060
Change in Total Area of Fluorescein Leakage (Center Subfield) From Baseline Over Time Month 12	-0.391 mm^2 Standard Deviation 0.3716	-.0208 mm^2 Standard Deviation 0.4075

SECONDARY outcome

Timeframe: Months 3, 6 and 12

Fluorescein leakage area was assessed using Fluorescein angiography (FA) in conjunction with 7-field color fundus photography (CF) at Screening, Month 3, Month 6 and End of Study visit for both eyes

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg n=186 Participants PRN Intravitreal injection	Sham Injection n=90 Participants As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
Change in Total Area of Fluorescein Leakage (Inner Subfield) From Baseline Over Time Month 3	-1.869 mm^2 Standard Deviation 1.8071	0.111 mm^2 Standard Deviation 1.5497
Change in Total Area of Fluorescein Leakage (Inner Subfield) From Baseline Over Time Month 6	-1.642 mm^2 Standard Deviation 1.9570	-0.078 mm^2 Standard Deviation 1.6856
Change in Total Area of Fluorescein Leakage (Inner Subfield) From Baseline Over Time Month 12	-1.732 mm^2 Standard Deviation 1.8059	-0.823 mm^2 Standard Deviation 1.9650

SECONDARY outcome

Timeframe: Months 3, 6 and 12

Fluorescein leakage area was assessed using Fluorescein angiography (FA) in conjunction with 7-field color fundus photography (CF) at Screening, Month 3, Month 6 and End of Study visit for both eyes

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg n=186 Participants PRN Intravitreal injection	Sham Injection n=90 Participants As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
Change in Total Area of Fluorescein Leakage (Outer Subfield) From Baseline Over Time Month 3	-4.994 mm^2 Standard Deviation 5.4066	-0.600 mm^2 Standard Deviation 3.6646
Change in Total Area of Fluorescein Leakage (Outer Subfield) From Baseline Over Time Month 6	-4.654 mm^2 Standard Deviation 5.7504	-0.836 mm^2 Standard Deviation 4.2819
Change in Total Area of Fluorescein Leakage (Outer Subfield) From Baseline Over Time Month 12	-5.078 mm^2 Standard Deviation 5.9568	-2.797 mm^2 Standard Deviation 5.3702

SECONDARY outcome

Timeframe: Baseline, months 3, 6 and 12

Population: The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment group they had been assigned to at randomization. n=the number of patients with a value for both baseline and the specific post-baseline visit.

The VFQ-25 consists of 25 vision related questions across 11 vision related subscales, including general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision and peripheral vision, and a general health rating. Items are converted to a 0-100 scale on each subscale and for the composite score where higher scores represents better functioning.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg n=190 Participants PRN Intravitreal injection	Sham Injection n=93 Participants As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection
Change From Baseline in NEI-VFQ-25 Composite and Subscale Scores at Month 3, Month 6 and Month 12 Change from Baseline at M3 (n=187,91)	5.8 Scores on a Scale Standard Deviation 10.85	-1.1 Scores on a Scale Standard Deviation 11.21
Change From Baseline in NEI-VFQ-25 Composite and Subscale Scores at Month 3, Month 6 and Month 12 Change from Baseline at M6 (n=185,88)	7.7 Scores on a Scale Standard Deviation 11.88	0.1 Scores on a Scale Standard Deviation 13.95
Change From Baseline in NEI-VFQ-25 Composite and Subscale Scores at Month 3, Month 6 and Month 12 Change from Baseline at M12 (n=176,88)	9.6 Scores on a Scale Standard Deviation 13.45	3.3 Scores on a Scale Standard Deviation 13.52

Adverse Events

Ranibizumab 0.5 mg

Serious events: 13 serious events

Other events: 119 other events

Deaths: 0 deaths

Sham With Ranibizumab 0.5 mg

Serious events: 3 serious events

Other events: 46 other events

Deaths: 0 deaths

Sham Without Ranibizumab 0.5 mg

Serious events: 3 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis

Phone: 862-778-8300

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 or disclosure of trial results in their entirety
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Ranibizumab 0.5 mg n=190 participants at risk PRN Intravitreal injection	Sham With Ranibizumab 0.5 mg n=66 participants at risk As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection	Sham Without Ranibizumab 0.5 mg n=26 participants at risk sham + ranibizumab 0.5 mg PRN as of Month 6 (hereafter referred to as sham group up to Month 6 and sham with ranibizumab or sham without ranibizumab after Month 6)
Cardiac disorders Atrial fibrillation	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Cardiac disorders Cardiac failure	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Cardiac disorders Cardiac valve disease	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Cardiac disorders Coronary artery disease	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	3.8% 1/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Endocrine disorders Hyperthyroidism	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Eye disorders Cataract	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Eye disorders Macular hole	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Gastrointestinal disorders Colitis ulcerative	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Hepatobiliary disorders Cholecystitis chronic	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	3.8% 1/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Infections and infestations Pneumonia	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Injury, poisoning and procedural complications Clavicle fracture	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Injury, poisoning and procedural complications Contusion	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Injury, poisoning and procedural complications Fibula fracture	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Injury, poisoning and procedural complications Lower limb fracture	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Injury, poisoning and procedural complications Post concussion syndrome	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Injury, poisoning and procedural complications Tibia fracture	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Injury, poisoning and procedural complications Ulna fracture	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Musculoskeletal and connective tissue disorders Arthralgia	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Musculoskeletal and connective tissue disorders Synovial cyst	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Nervous system disorders Cluster headache	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Nervous system disorders Transient ischaemic attack	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	3.8% 1/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Nervous system disorders Vertebrobasilar insufficiency	1.1% 2/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Vascular disorders Haematoma	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Vascular disorders Hypertension	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.

Other adverse events
Measure	Ranibizumab 0.5 mg n=190 participants at risk PRN Intravitreal injection	Sham With Ranibizumab 0.5 mg n=66 participants at risk As of Month 6 ranibizumab 0.5 mg PRN intravitreal injection	Sham Without Ranibizumab 0.5 mg n=26 participants at risk sham + ranibizumab 0.5 mg PRN as of Month 6 (hereafter referred to as sham group up to Month 6 and sham with ranibizumab or sham without ranibizumab after Month 6)
Investigations Protein urine present	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Investigations Visual acuity tests abnormal	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Investigations Weight decreased	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Metabolism and nutrition disorders Diabetes mellitus	1.1% 2/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	3.8% 1/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Metabolism and nutrition disorders Gout	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	3.8% 1/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Metabolism and nutrition disorders Hyperlipidaemia	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Musculoskeletal and connective tissue disorders Arthralgia	3.2% 6/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Musculoskeletal and connective tissue disorders Arthropathy	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	3.8% 1/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Musculoskeletal and connective tissue disorders Back pain	1.1% 2/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	3.8% 1/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Musculoskeletal and connective tissue disorders Fasciitis	1.1% 2/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Musculoskeletal and connective tissue disorders Gouty arthritis	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Musculoskeletal and connective tissue disorders Pain in extremity	2.1% 4/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	3.8% 1/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	1.1% 2/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	7.7% 2/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	3.8% 1/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Nervous system disorders Balance disorder	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Nervous system disorders Dizziness	3.2% 6/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	3.0% 2/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Nervous system disorders Headache	5.8% 11/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	3.0% 2/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Nervous system disorders Syncope	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Psychiatric disorders Insomnia	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	4.5% 3/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Reproductive system and breast disorders Breast cyst	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Respiratory, thoracic and mediastinal disorders Cough	4.7% 9/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	3.0% 2/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	11.5% 3/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.1% 4/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	3.0% 2/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	3.8% 1/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Skin and subcutaneous tissue disorders Rash	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Skin and subcutaneous tissue disorders Urticaria	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Skin and subcutaneous tissue disorders Urticaria papular	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Vascular disorders Aortic arteriosclerosis	1.1% 2/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Vascular disorders Hypertension	8.4% 16/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	12.1% 8/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	15.4% 4/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Blood and lymphatic system disorders Anaemia	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	3.8% 1/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	3.8% 1/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Cardiac disorders Angina pectoris	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	3.8% 1/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Cardiac disorders Arteriosclerosis coronary artery	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Cardiac disorders Coronary artery disease	2.1% 4/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Eye disorders Age-related macular degeneration	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	3.8% 1/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Eye disorders Angle closure glaucoma	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Eye disorders Cataract	1.1% 2/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.5% 1/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Eye disorders Conjunctival deposit	1.1% 2/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Eye disorders Conjunctival haemorrhage	10.5% 20/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	6.1% 4/66 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/26 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.