Trial Outcomes & Findings for Efficacy and Safety of PRO-155 on Inflammation of the Conjunctival Surface in Subjects With Grade I-III Pterygium vs Placebo. (NCT NCT03521791)

Last Updated: 2019-11-20

Results Overview

Conjunctival hyperemia will be evaluated as an ordinal variable, by direct observation and staged using the Efron scale as Normal / Very Light / Mild / Moderate / Severe. Based on this scale, the normal and mild stages are considered without pathologies or normal. Mild, moderate and severe are considered pathological.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

166 participants

Primary outcome timeframe

will be evaluated at the end of the treatment at the final visit (day 21)

Results posted on

2019-11-20

Participant Flow

Participant milestones

Participant milestones
Measure	PRO-155 Pro-155: 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac for 20 days PRO-155: PRO-155 (Zebesten ofteno®) Active agent: bromfenac 0.90 mg / mL, dropper bottle of low density polyethylene for multidose administration in the form of an ophthalmic solution of 5 mL (milliliters). Sanitary registry in Mexico: 108M2014 Sodium hyaluronate 0.4% \[Lagricel ofteno®\] 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac	Placebo Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac Placebo: The placebo is constituted by agents, additives and vehicles, of the formulation PRO-155 without pharmacological activity. It is dispensed in dropper bottle of low density polyethylene for multi-dose administration in the form of ophthalmic solution of 5 mL Sodium hyaluronate 0.4% (Lagricel ofteno®) 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac
Overall Study STARTED	76	90
Overall Study COMPLETED	69	73
Overall Study NOT COMPLETED	7	17

Reasons for withdrawal

Reasons for withdrawal
Measure	PRO-155 Pro-155: 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac for 20 days PRO-155: PRO-155 (Zebesten ofteno®) Active agent: bromfenac 0.90 mg / mL, dropper bottle of low density polyethylene for multidose administration in the form of an ophthalmic solution of 5 mL (milliliters). Sanitary registry in Mexico: 108M2014 Sodium hyaluronate 0.4% \[Lagricel ofteno®\] 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac	Placebo Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac Placebo: The placebo is constituted by agents, additives and vehicles, of the formulation PRO-155 without pharmacological activity. It is dispensed in dropper bottle of low density polyethylene for multi-dose administration in the form of ophthalmic solution of 5 mL Sodium hyaluronate 0.4% (Lagricel ofteno®) 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac
Overall Study Protocol Violation	7	17

Baseline Characteristics

Efficacy and Safety of PRO-155 on Inflammation of the Conjunctival Surface in Subjects With Grade I-III Pterygium vs Placebo.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PRO-155 n=82 eyes Pro-155: 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac for 20 days PRO-155: PRO-155 (Zebesten ofteno®) Active agent: bromfenac 0.90 mg / mL, dropper bottle of low density polyethylene for multidose administration in the form of an ophthalmic solution of 5 mL (milliliters). Sanitary registry in Mexico: 108M2014 Sodium hyaluronate 0.4% \[Lagricel ofteno®\] 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac	Placebo n=84 eyes Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac Placebo: The placebo is constituted by agents, additives and vehicles, of the formulation PRO-155 without pharmacological activity. It is dispensed in dropper bottle of low density polyethylene for multi-dose administration in the form of ophthalmic solution of 5 mL Sodium hyaluronate 0.4% (Lagricel ofteno®) 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac	Total n=166 eyes Total of all reporting groups
Age, Continuous	53.8 years STANDARD_DEVIATION 13.3 • n=93 Participants	57.17 years STANDARD_DEVIATION 14.4 • n=4 Participants	55.51 years STANDARD_DEVIATION 13.45 • n=27 Participants
Sex: Female, Male Female	30 Participants n=93 Participants	30 Participants n=4 Participants	60 Participants n=27 Participants
Sex: Female, Male Male	11 Participants n=93 Participants	12 Participants n=4 Participants	23 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) White	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) More than one race	41 Participants n=93 Participants	42 Participants n=4 Participants	83 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: will be evaluated at the end of the treatment at the final visit (day 21)

Population: statistical analysis by protocol (PP)

Outcome measures

Outcome measures
Measure	PRO-155 n=69 eyes Pro-155: 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac for 20 days PRO-155: PRO-155 (Zebesten ofteno®) Active agent: bromfenac 0.90 mg / mL, dropper bottle of low density polyethylene for multidose administration in the form of an ophthalmic solution of 5 mL (milliliters). Sanitary registry in Mexico: 108M2014 Sodium hyaluronate 0.4% \[Lagricel ofteno®\] 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac	Placebo n=73 eyes Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac Placebo: The placebo is constituted by agents, additives and vehicles, of the formulation PRO-155 without pharmacological activity. It is dispensed in dropper bottle of low density polyethylene for multi-dose administration in the form of ophthalmic solution of 5 mL Sodium hyaluronate 0.4% (Lagricel ofteno®) 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac
Conjunctival Hyperemia (CH) Mild	25 eyes	36 eyes
Conjunctival Hyperemia (CH) Moderate	5 eyes	8 eyes
Conjunctival Hyperemia (CH) Normal	0 eyes	0 eyes
Conjunctival Hyperemia (CH) Very mild	39 eyes	29 eyes
Conjunctival Hyperemia (CH) Severe	0 eyes	0 eyes

PRIMARY outcome

Timeframe: will be evaluated at the end of the treatment at the final visit (day 21)

Population: Statistical analysis was performed by protocol (PP)

breakup time lacrimal film is a continuous variable that will be measured in seconds, evaluating the time it takes to break it, is done by direct counting and the normality range and mayor to 10 seconds.

Outcome measures

Outcome measures
Measure	PRO-155 n=69 eyes Pro-155: 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac for 20 days PRO-155: PRO-155 (Zebesten ofteno®) Active agent: bromfenac 0.90 mg / mL, dropper bottle of low density polyethylene for multidose administration in the form of an ophthalmic solution of 5 mL (milliliters). Sanitary registry in Mexico: 108M2014 Sodium hyaluronate 0.4% \[Lagricel ofteno®\] 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac	Placebo n=73 eyes Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac Placebo: The placebo is constituted by agents, additives and vehicles, of the formulation PRO-155 without pharmacological activity. It is dispensed in dropper bottle of low density polyethylene for multi-dose administration in the form of ophthalmic solution of 5 mL Sodium hyaluronate 0.4% (Lagricel ofteno®) 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac
Breakup Time (BUT)	8.29 seconds Standard Deviation 2.2	7.63 seconds Standard Deviation 2.3

SECONDARY outcome

Timeframe: will be evaluated at the end of the treatment at the final visit (day 21)

The epithelial defects will be evaluated by means of two stains, green lysine and fluorescein, it is a discrete variable that will be realized by direct observation, it will be staged according to the degrees of the oxford scale that go from 0 to 5 (0-V) according to its severity, where 0 is the normal lower limit and 5 the upper limit of defects.

Outcome measures

Outcome measures
Measure	PRO-155 n=69 eyes Pro-155: 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac for 20 days PRO-155: PRO-155 (Zebesten ofteno®) Active agent: bromfenac 0.90 mg / mL, dropper bottle of low density polyethylene for multidose administration in the form of an ophthalmic solution of 5 mL (milliliters). Sanitary registry in Mexico: 108M2014 Sodium hyaluronate 0.4% \[Lagricel ofteno®\] 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac	Placebo n=73 eyes Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac Placebo: The placebo is constituted by agents, additives and vehicles, of the formulation PRO-155 without pharmacological activity. It is dispensed in dropper bottle of low density polyethylene for multi-dose administration in the form of ophthalmic solution of 5 mL Sodium hyaluronate 0.4% (Lagricel ofteno®) 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac
Epithelial Defects (ED) Green Lissamine Green lissamine grade 0	41 eyes	44 eyes
Epithelial Defects (ED) Green Lissamine Green lissamine grade 3	3 eyes	0 eyes
Epithelial Defects (ED) Green Lissamine Green lissamine grade 1	21 eyes	21 eyes
Epithelial Defects (ED) Green Lissamine Green lissamine grade 2	4 eyes	8 eyes
Epithelial Defects (ED) Green Lissamine Green lissamine grade 4	0 eyes	0 eyes
Epithelial Defects (ED) Green Lissamine Green lissamine grade 5	0 eyes	0 eyes

SECONDARY outcome

Timeframe: will be evaluated at the end of the treatment at the final visit (day 21)

Population: the statistical analysis was carried out by protocol (PP)

the intraocular pressure will be evaluated by means of the Goldman applanation tonometry whose unit of measurement is millimeters of mercury (mmHg), it is a continuous variable and its normality range is between 11 - 21 mmHg

Outcome measures

Outcome measures
Measure	PRO-155 n=69 eyes Pro-155: 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac for 20 days PRO-155: PRO-155 (Zebesten ofteno®) Active agent: bromfenac 0.90 mg / mL, dropper bottle of low density polyethylene for multidose administration in the form of an ophthalmic solution of 5 mL (milliliters). Sanitary registry in Mexico: 108M2014 Sodium hyaluronate 0.4% \[Lagricel ofteno®\] 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac	Placebo n=73 eyes Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac Placebo: The placebo is constituted by agents, additives and vehicles, of the formulation PRO-155 without pharmacological activity. It is dispensed in dropper bottle of low density polyethylene for multi-dose administration in the form of ophthalmic solution of 5 mL Sodium hyaluronate 0.4% (Lagricel ofteno®) 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac
Intraocular Pressure (IOP)	12.45 mmHg Standard Deviation 2.1	13.08 mmHg Standard Deviation 1.8

SECONDARY outcome

Timeframe: will be evaluated at the end of the treatment at the final visit (day 36)

Population: The analysis of adverse events was done by intention to treat (ITT)

primary security variable the adverse events will be evaluated with a scale of Present / Absent, it is a nominal variable, the normal value is absent. Adverse events that are reported until the safety call to the 36th day of the study will be considered for this variable

Outcome measures

Outcome measures
Measure	PRO-155 n=47 Participants Pro-155: 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac for 20 days PRO-155: PRO-155 (Zebesten ofteno®) Active agent: bromfenac 0.90 mg / mL, dropper bottle of low density polyethylene for multidose administration in the form of an ophthalmic solution of 5 mL (milliliters). Sanitary registry in Mexico: 108M2014 Sodium hyaluronate 0.4% \[Lagricel ofteno®\] 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac	Placebo n=52 Participants Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac Placebo: The placebo is constituted by agents, additives and vehicles, of the formulation PRO-155 without pharmacological activity. It is dispensed in dropper bottle of low density polyethylene for multi-dose administration in the form of ophthalmic solution of 5 mL Sodium hyaluronate 0.4% (Lagricel ofteno®) 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac
Presence of Adverse Events (EAS)	13 Participants	19 Participants

SECONDARY outcome

Timeframe: will be evaluated at the end of the treatment at the final visit (day 21)

The visual capacity variable will be reported using as a unit of measure a fraction, this is taken from a visual test with the Snellen primer, it is a Nominal type variable. where the optimal vision is 20/20.

Outcome measures

Outcome measures
Measure	PRO-155 n=69 eyes Pro-155: 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac for 20 days PRO-155: PRO-155 (Zebesten ofteno®) Active agent: bromfenac 0.90 mg / mL, dropper bottle of low density polyethylene for multidose administration in the form of an ophthalmic solution of 5 mL (milliliters). Sanitary registry in Mexico: 108M2014 Sodium hyaluronate 0.4% \[Lagricel ofteno®\] 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac	Placebo n=73 eyes Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac Placebo: The placebo is constituted by agents, additives and vehicles, of the formulation PRO-155 without pharmacological activity. It is dispensed in dropper bottle of low density polyethylene for multi-dose administration in the form of ophthalmic solution of 5 mL Sodium hyaluronate 0.4% (Lagricel ofteno®) 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac
Visual Capacity	0.043 LogMAR Standard Deviation 0.1	0.059 LogMAR Standard Deviation 0.2

SECONDARY outcome

Timeframe: will be evaluated at the end of the treatment at the final visit (day 21)

Population: the statistical analysis was carried out by protocol (PP)

In a normal eye there is no presence of chemosis (it is a sign of irritation of the eye, in which the outer covering of the eye can look like a large blister) its presence indicates a pathological state and it will be evaluated if the subjects present it. The chemosis will be evaluated, as a nominal variable, by direct observation and it will be staged as present and absent, where the normality is that said variable is absent.

Outcome measures

Outcome measures
Measure	PRO-155 n=69 eyes Pro-155: 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac for 20 days PRO-155: PRO-155 (Zebesten ofteno®) Active agent: bromfenac 0.90 mg / mL, dropper bottle of low density polyethylene for multidose administration in the form of an ophthalmic solution of 5 mL (milliliters). Sanitary registry in Mexico: 108M2014 Sodium hyaluronate 0.4% \[Lagricel ofteno®\] 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac	Placebo n=73 eyes Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac Placebo: The placebo is constituted by agents, additives and vehicles, of the formulation PRO-155 without pharmacological activity. It is dispensed in dropper bottle of low density polyethylene for multi-dose administration in the form of ophthalmic solution of 5 mL Sodium hyaluronate 0.4% (Lagricel ofteno®) 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac
Number of Eyes With Chemosis	0 eyes	0 eyes

SECONDARY outcome

Timeframe: will be evaluated at the end of the treatment at the final visit (day 21)

Population: the statistical analysis was carried out by protocol (PP)

Foreign body sensation will be evaluated, as a nominal variable, by direct observation and it will be staged as present and absent, where the normality is that said variable is absent.

Outcome measures

Outcome measures
Measure	PRO-155 n=69 eyes Pro-155: 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac for 20 days PRO-155: PRO-155 (Zebesten ofteno®) Active agent: bromfenac 0.90 mg / mL, dropper bottle of low density polyethylene for multidose administration in the form of an ophthalmic solution of 5 mL (milliliters). Sanitary registry in Mexico: 108M2014 Sodium hyaluronate 0.4% \[Lagricel ofteno®\] 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac	Placebo n=73 eyes Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac Placebo: The placebo is constituted by agents, additives and vehicles, of the formulation PRO-155 without pharmacological activity. It is dispensed in dropper bottle of low density polyethylene for multi-dose administration in the form of ophthalmic solution of 5 mL Sodium hyaluronate 0.4% (Lagricel ofteno®) 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac
Number of Eyes With Foreign Body Sensation (FBS)	10 eyes	18 eyes

SECONDARY outcome

Timeframe: will be evaluated at the end of the treatment at the final visit (day 21)

Population: the statistical analysis was carried out by protocol (PP)

Outcome measures

Outcome measures
Measure	PRO-155 n=69 eyes Pro-155: 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac for 20 days PRO-155: PRO-155 (Zebesten ofteno®) Active agent: bromfenac 0.90 mg / mL, dropper bottle of low density polyethylene for multidose administration in the form of an ophthalmic solution of 5 mL (milliliters). Sanitary registry in Mexico: 108M2014 Sodium hyaluronate 0.4% \[Lagricel ofteno®\] 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac	Placebo n=73 eyes Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac Placebo: The placebo is constituted by agents, additives and vehicles, of the formulation PRO-155 without pharmacological activity. It is dispensed in dropper bottle of low density polyethylene for multi-dose administration in the form of ophthalmic solution of 5 mL Sodium hyaluronate 0.4% (Lagricel ofteno®) 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac
Epithelial Defects (ED) Fluorescein Stain Fluorescein Grade 3	0 eyes	0 eyes
Epithelial Defects (ED) Fluorescein Stain Fluorescein Grade 4	0 eyes	0 eyes
Epithelial Defects (ED) Fluorescein Stain Fluorescein Grade 0	31 eyes	31 eyes
Epithelial Defects (ED) Fluorescein Stain Fluorescein Grade 1	27 eyes	33 eyes
Epithelial Defects (ED) Fluorescein Stain Fluorescein Grade 2	11 eyes	9 eyes
Epithelial Defects (ED) Fluorescein Stain Fluorescein Grade 5	0 eyes	0 eyes

OTHER_PRE_SPECIFIED outcome

Timeframe: will be evaluated at the end of the treatment at the final visit (day 21)

Population: the statistical analysis was carried out by protocol (PP)

primary tolerability variable Ocular burning is a nominal variable that will be evaluated by direct questioning to the research subject, then it will be staged according to the following scale: Severity: Absent, very mild, mild, moderate and severe, where the normality of severity is absent.Frequency: At all times, almost at all times, 50% of the time, almost in no time, at any time. where the normality of the frequency is in no time.

Outcome measures

Outcome measures
Measure	PRO-155 n=69 eyes Pro-155: 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac for 20 days PRO-155: PRO-155 (Zebesten ofteno®) Active agent: bromfenac 0.90 mg / mL, dropper bottle of low density polyethylene for multidose administration in the form of an ophthalmic solution of 5 mL (milliliters). Sanitary registry in Mexico: 108M2014 Sodium hyaluronate 0.4% \[Lagricel ofteno®\] 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac	Placebo n=73 eyes Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac Placebo: The placebo is constituted by agents, additives and vehicles, of the formulation PRO-155 without pharmacological activity. It is dispensed in dropper bottle of low density polyethylene for multi-dose administration in the form of ophthalmic solution of 5 mL Sodium hyaluronate 0.4% (Lagricel ofteno®) 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac
Number of Eyes With Ocular Burning (OB)	8 eyes	11 eyes

Adverse Events

PRO-155

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

PhD. Ricardo Llamas

Laboratorios Sophia

Phone: +52 (33) 3001 4200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The principal investigator can not publish any information about the investigation without prior written authorization from the atrocifier
Publication restrictions are in place

Restriction type: OTHER

Measure	PRO-155 n=76 participants at risk Pro-155: 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac for 20 days PRO-155: PRO-155 (Zebesten ofteno®) Active agent: bromfenac 0.90 mg / mL, dropper bottle of low density polyethylene for multidose administration in the form of an ophthalmic solution of 5 mL (milliliters). Sanitary registry in Mexico: 108M2014 Sodium hyaluronate 0.4% \[Lagricel ofteno®\] 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac	Placebo n=90 participants at risk Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac Placebo: The placebo is constituted by agents, additives and vehicles, of the formulation PRO-155 without pharmacological activity. It is dispensed in dropper bottle of low density polyethylene for multi-dose administration in the form of ophthalmic solution of 5 mL Sodium hyaluronate 0.4% (Lagricel ofteno®) 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac
Gastrointestinal disorders sickness	0.00% 0/76 • Adverse events were monitored and recorded throughout the study, an average of 8 months.	1.1% 1/90 • Number of events 1 • Adverse events were monitored and recorded throughout the study, an average of 8 months.
Gastrointestinal disorders vomit	0.00% 0/76 • Adverse events were monitored and recorded throughout the study, an average of 8 months.	1.1% 1/90 • Number of events 1 • Adverse events were monitored and recorded throughout the study, an average of 8 months.
Eye disorders photophobia	2.6% 2/76 • Number of events 2 • Adverse events were monitored and recorded throughout the study, an average of 8 months.	4.4% 4/90 • Number of events 4 • Adverse events were monitored and recorded throughout the study, an average of 8 months.
Eye disorders ocular burning	6.6% 5/76 • Number of events 5 • Adverse events were monitored and recorded throughout the study, an average of 8 months.	5.6% 5/90 • Number of events 5 • Adverse events were monitored and recorded throughout the study, an average of 8 months.
Eye disorders tearing	0.00% 0/76 • Adverse events were monitored and recorded throughout the study, an average of 8 months.	1.1% 1/90 • Number of events 1 • Adverse events were monitored and recorded throughout the study, an average of 8 months.
Metabolism and nutrition disorders hypoglycemia	0.00% 0/76 • Adverse events were monitored and recorded throughout the study, an average of 8 months.	1.1% 1/90 • Number of events 1 • Adverse events were monitored and recorded throughout the study, an average of 8 months.
Eye disorders conjunctival hyperemia	3.9% 3/76 • Number of events 3 • Adverse events were monitored and recorded throughout the study, an average of 8 months.	12.2% 11/90 • Number of events 11 • Adverse events were monitored and recorded throughout the study, an average of 8 months.
Eye disorders ocular pain	0.00% 0/76 • Adverse events were monitored and recorded throughout the study, an average of 8 months.	2.2% 2/90 • Number of events 2 • Adverse events were monitored and recorded throughout the study, an average of 8 months.
Eye disorders Eye pruritus	0.00% 0/76 • Adverse events were monitored and recorded throughout the study, an average of 8 months.	3.3% 3/90 • Number of events 3 • Adverse events were monitored and recorded throughout the study, an average of 8 months.
Eye disorders Dry-eye feeling	0.00% 0/76 • Adverse events were monitored and recorded throughout the study, an average of 8 months.	1.1% 1/90 • Number of events 1 • Adverse events were monitored and recorded throughout the study, an average of 8 months.
Eye disorders Foreign body sensation in eyes	2.6% 2/76 • Number of events 2 • Adverse events were monitored and recorded throughout the study, an average of 8 months.	3.3% 3/90 • Number of events 3 • Adverse events were monitored and recorded throughout the study, an average of 8 months.
Eye disorders Stye	1.3% 1/76 • Number of events 1 • Adverse events were monitored and recorded throughout the study, an average of 8 months.	0.00% 0/90 • Adverse events were monitored and recorded throughout the study, an average of 8 months.
Nervous system disorders Headache	1.3% 1/76 • Number of events 1 • Adverse events were monitored and recorded throughout the study, an average of 8 months.	0.00% 0/90 • Adverse events were monitored and recorded throughout the study, an average of 8 months.
Eye disorders Eye irritation	0.00% 0/76 • Adverse events were monitored and recorded throughout the study, an average of 8 months.	1.1% 1/90 • Number of events 1 • Adverse events were monitored and recorded throughout the study, an average of 8 months.
General disorders sore throat	1.3% 1/76 • Number of events 1 • Adverse events were monitored and recorded throughout the study, an average of 8 months.	0.00% 0/90 • Adverse events were monitored and recorded throughout the study, an average of 8 months.
Eye disorders Corneal epithelium defect	1.3% 1/76 • Number of events 1 • Adverse events were monitored and recorded throughout the study, an average of 8 months.	0.00% 0/90 • Adverse events were monitored and recorded throughout the study, an average of 8 months.