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

• Sponsor: Laboratorios Sophia S.A de C.V. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03521791
• Collaborator: (none)
• Enrollment: 166
• Locations: 3
• Arms: 2
• Actual Duration (Months): 10.6
• Patients Per Site: 55.3
• Patients Per Site Per Month: 5.2

Study Details

Study Description

Brief Summary

Title of the study Efficacy and safety of PRO-155 (Zebesten ofteno®) on inflammation of the conjunctival surface in subjects with grade I-III pterygium vs placebo.

Hypothesis H0. The Zebesten® ophthalmic solution (bromfenac 0.09%) is less effective and safe than placebo in reducing conjunctival hyperemia in subjects with grade I-III pterygium.

H1 The Zebesten® ophthalmic solution (bromfenac 0.09%) is more effective and safe than placebo in reducing conjunctival hyperemia in subjects with grade I-III pterygium.

Objective

To evaluate the efficacy and safety of PRO-155 (bromfenac 009%) ophthalmic solution in the treatment of conjunctival hyperemia and ocular surface inflammation in a clinical model of pterygium grade I to III.

Condition or Disease	Intervention/Treatment	Phase
Pterygium; Ocular Pain; Ocular Inflammation; Post-surgical Inflammation	Drug: PRO-155; Other: Placebo	Phase 4

Detailed Description

Variables to be evaluated Visual ability Intraocular pressure. Ocular surface Exploration of the previous segment. Exploration of the posterior segment. Lacrimal rupture time. Corneal de-epithelialization Conjunctival de-epithelialization Adverse events.

PHARMACOLOGICAL INTERVENTION

The pharmacological intervention will consist of the instillation of the ophthalmological solution in the conjunctival cul-de-sac, during the waking period, to any of the following study groups:

• Group 1:

• Sodium hyaluronate 0.4% [Lagricel ofteno®] 1 drop 3 times a day in the period of vigil in the conjunctival sac fund (the following application scheme is suggested: start: 7:00 ± 1 hours, continuation: 15:00 ± 1 hour and term: at 19:00 ± 1 hours) for 20 days

• Pro-155 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac (the following application scheme is recommended: start: 7:15 ± 1 hours and term: at 19:15 ± 1 hours) during 20 days

• Group 2:

• Sodium hyaluronate 0.4% [Lagricel ofteno®] 1 drop 3 times a day in the period of vigil in the conjunctival sac fund (the following application scheme is suggested: start: 7:00 ± 1 hours, continuation: 15:00 ± 1 hour and term: at 19:00 ± 1 hours) for 20 days

• Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac (the following application scheme is recommended: start: 7:15 ± 1 hours and term: at 19:15 ± 1 hours) for 20 days

Study Design

• Study Type: Interventional
• Actual Enrollment: 166 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A controlled, randomized, double-blind, masked clinical trial comparing the safety and efficacy of PRO-155 in the treatment of conjunctival hyperemia in pterygium I to III compared to placebo.A controlled, randomized, double-blind, masked clinical trial comparing the safety and efficacy of PRO-155 in the treatment of conjunctival hyperemia in pterygium I to III compared to placebo.
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: The double-blind study is a procedure in which the subject and the principal investigator do not know which of the intervention groups was assigned to the subject of the study. To achieve the blinding of the drug, both the investigational drug and the placebo, will be packed in the same bottle, containing the same legends on the label. The blinding codes are protected by a person outside the study designated by the sponsor. The codes are also available in the research center (fully sealed), so that they can be consulted by the Investigator in the event that the subject presents a serious adverse event, prior authorization of the study sponsor, as well as strict continuous blindness during the analysis of data.
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of PRO-155 (Zebesten Ofteno®) on Inflammation of the Conjunctival Surface in Subjects With Grade I-III Pterygium vs Placebo.
• Actual Study Start Date: Dec 13, 2017
• Actual Primary Completion Date: Sep 14, 2018
• Actual Study Completion Date: Oct 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PRO-155 Pro-155: 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac for 20 days	Drug: 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; Other Names: zebesten bromfenac
Placebo Comparator: Placebo Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac	Other: 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

Outcome Measures

Primary Outcome Measures

1. Conjunctival Hyperemia (CH) [will be evaluated at the end of the treatment at the final visit (day 21)]

   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.

2. Breakup Time (BUT) [will be evaluated at the end of the treatment at the final visit (day 21)]

   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.

Secondary Outcome Measures

1. Epithelial Defects (ED) Green Lissamine [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.

2. Intraocular Pressure (IOP) [will be evaluated at the end of the treatment at the final visit (day 21)]

   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

3. Presence of Adverse Events (EAS) [will be evaluated at the end of the treatment at the final visit (day 36)]

   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

4. Visual Capacity [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.

5. Number of Eyes With Chemosis [will be evaluated at the end of the treatment at the final visit (day 21)]

   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.

6. Number of Eyes With Foreign Body Sensation (FBS) [will be evaluated at the end of the treatment at the final visit (day 21)]

   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.

7. Epithelial Defects (ED) Fluorescein Stain [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.

Other Outcome Measures

1. Number of Eyes With Ocular Burning (OB) [will be evaluated at the end of the treatment at the final visit (day 21)]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age of 18 to 90 years.

• Both genders.

• Clinical diagnosis of grade I to III pterygium (temporal, nasal, or bitemporal).

• Possibility of going to the revisions when indicated.

Exclusion Criteria:

• Subjects with topical or systemic medication that interfere decisively in the results of the study; such as topical immunomodulators, NSAIDs, antihistamines, corticosteroids, artificial tears with conservative, vasoconstrictors etc.

• Subjects (female) with active sexual life who do not use a contraceptive method.

• Subjects of the female sex in a pregnant state or who are breastfeeding.

• Subjects of the female sex with pregnancy test in positive urine.

• Positive substance abuse

• Subjects who have participated in any clinical research study in the last 40 days.

• Subjects legally or mentally incapacitated to give their informed consent for their participation in this study.

• Subjects that can not comply with the appointments or with all the requirements of the Protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	catarata y glaucoma de occidente S.A de C.V.	Guadalajara	Jalisco	Mexico	44160
2	Novam y Vita	Guadalajara	Jalisco	Mexico	44620
3	Consultorio PRivado Miguel Angel Villanueva	Ciudad de México		Mexico	06700

Sponsors and Collaborators

• Laboratorios Sophia S.A de C.V.

Investigators

• Study Director: Leopoldo Baiza Durán, MD, Laboratorios Sophia S.A de C.V.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 1, 2016

More Information

Publications

None provided.

• Responsible Party: Laboratorios Sophia S.A de C.V.
• ClinicalTrials.gov Identifier: NCT03521791
• Other Study ID Numbers: SOPH155-0415/IV
• First Posted: May 11, 2018
• Last Update Posted: Nov 20, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Laboratorios Sophia S.A de C.V.: zebesten; ocular anti-inflammatory; ocular analgesic; pterygium; anti-inflammatory non-steroidal ophthalmic
• Additional relevant MeSH terms: Pterygium; Inflammation; Bromfenac

Study Results

Participant Flow

Arm/Group Title	PRO-155	Placebo
Arm/Group Description	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 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
Period Title: Overall Study
STARTED	76	90
COMPLETED	69	73
NOT COMPLETED	7	17

Baseline Characteristics

Arm/Group Title	PRO-155	Placebo	Total
Arm/Group Description	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 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 of all reporting groups
Overall Participants	41	42	83
Overall eyes	82	84	166
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.8 (13.3)	57.17 (14.4)	55.51 (13.45)
Sex: Female, Male (Count of Participants)
Female	30 73.2%	30 71.4%	60 72.3%
Male	11 26.8%	12 28.6%	23 27.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	41 100%	42 100%	83 100%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Conjunctival Hyperemia (CH)
Description	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.
Time Frame	will be evaluated at the end of the treatment at the final visit (day 21)

Outcome Measure Data

Analysis Population Description

statistical analysis by protocol (PP)

Arm/Group Title	PRO-155	Placebo
Arm/Group Description	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 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
Measure Participants	41	42
Measure eyes	69	73
Normal	0	0
Very mild	39	29
Mild	25	36
Moderate	5	8
Severe	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-155
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	it is considered not inferior if the differences between the groups do not exceed 20%.
Statistical Test of Hypothesis	p-Value	0.133
	Comments
	Method	Chi-squared, Corrected
	Comments

2. Primary Outcome

Title	Breakup Time (BUT)
Description	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.
Time Frame	will be evaluated at the end of the treatment at the final visit (day 21)

Outcome Measure Data

Analysis Population Description

Statistical analysis was performed by protocol (PP)

Arm/Group Title	PRO-155	Placebo
Arm/Group Description	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 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
Measure Participants	41	42
Measure eyes	69	73
Mean (Standard Deviation) [seconds]	8.29 (2.2)	7.63 (2.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-155, Placebo
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	it is considered not inferior if the differences between the groups do not exceed 20%.
Statistical Test of Hypothesis	p-Value	0.045
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Epithelial Defects (ED) Green Lissamine
Description	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.
Time Frame	will be evaluated at the end of the treatment at the final visit (day 21)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PRO-155	Placebo
Arm/Group Description	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 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
Measure Participants	41	42
Measure eyes	69	73
Green lissamine grade 0	41	44
Green lissamine grade 1	21	21
Green lissamine grade 2	4	8
Green lissamine grade 3	3	0
Green lissamine grade 4	0	0
Green lissamine grade 5	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-155, Placebo
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	it is considered not inferior if the differences between the groups do not exceed 20%.
Statistical Test of Hypothesis	p-Value	0.333
	Comments
	Method	Chi-squared, Corrected
	Comments

4. Secondary Outcome

Title	Intraocular Pressure (IOP)
Description	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
Time Frame	will be evaluated at the end of the treatment at the final visit (day 21)

Outcome Measure Data

Analysis Population Description

the statistical analysis was carried out by protocol (PP)

Arm/Group Title	PRO-155	Placebo
Arm/Group Description	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 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
Measure Participants	41	42
Measure eyes	69	73
Mean (Standard Deviation) [mmHg]	12.45 (2.1)	13.08 (1.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-155, Placebo
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	it is considered not inferior if the differences between the groups do not exceed 20%.
Statistical Test of Hypothesis	p-Value	0.058
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Presence of Adverse Events (EAS)
Description	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
Time Frame	will be evaluated at the end of the treatment at the final visit (day 36)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	PRO-155	Placebo
Arm/Group Description	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 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
Measure Participants	47	52
Count of Participants [Participants]	13 31.7%	19 45.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-155, Placebo
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	it is considered not inferior if the differences between the groups do not exceed 20%.
Statistical Test of Hypothesis	p-Value	0.394
	Comments
	Method	Fisher Exact
	Comments

6. Secondary Outcome

Title	Visual Capacity
Description	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.
Time Frame	will be evaluated at the end of the treatment at the final visit (day 21)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PRO-155	Placebo
Arm/Group Description	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 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
Measure Participants	41	42
Measure eyes	69	73
Mean (Standard Deviation) [LogMAR]	0.043 (0.1)	0.059 (0.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-155, Placebo
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	it is considered not inferior if the differences between the groups do not exceed 20%.
Statistical Test of Hypothesis	p-Value	0.056
	Comments
	Method	t-test, 2 sided
	Comments

7. Secondary Outcome

Title	Number of Eyes With Chemosis
Description	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.
Time Frame	will be evaluated at the end of the treatment at the final visit (day 21)

Outcome Measure Data

Analysis Population Description

the statistical analysis was carried out by protocol (PP)

Arm/Group Title	PRO-155	Placebo
Arm/Group Description	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 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
Measure Participants	41	42
Measure eyes	69	73
Count of Units [eyes]	0	0

8. Secondary Outcome

Title	Number of Eyes With Foreign Body Sensation (FBS)
Description	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.
Time Frame	will be evaluated at the end of the treatment at the final visit (day 21)

Outcome Measure Data

Analysis Population Description

the statistical analysis was carried out by protocol (PP)

Arm/Group Title	PRO-155	Placebo
Arm/Group Description	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 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
Measure Participants	41	42
Measure eyes	69	73
Count of Units [eyes]	10	18

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-155, Placebo
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	it is considered not inferior if the differences between the groups do not exceed 20%.
Statistical Test of Hypothesis	p-Value	0.114
	Comments
	Method	Fisher Exact
	Comments

9. Secondary Outcome

Title	Epithelial Defects (ED) Fluorescein Stain
Description	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.
Time Frame	will be evaluated at the end of the treatment at the final visit (day 21)

Outcome Measure Data

Analysis Population Description

the statistical analysis was carried out by protocol (PP)

Arm/Group Title	PRO-155	Placebo
Arm/Group Description	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 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
Measure Participants	41	42
Measure eyes	69	73
Fluorescein Grade 0	31	31
Fluorescein Grade 1	27	33
Fluorescein Grade 2	11	9
Fluorescein Grade 3	0	0
Fluorescein Grade 4	0	0
Fluorescein Grade 5	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-155, Placebo
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	it is considered not inferior if the differences between the groups do not exceed 20%.
Statistical Test of Hypothesis	p-Value	0.117
	Comments
	Method	Chi-squared, Corrected
	Comments

10. Other Pre-specified Outcome

Title	Number of Eyes With Ocular Burning (OB)
Description	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.
Time Frame	will be evaluated at the end of the treatment at the final visit (day 21)

Outcome Measure Data

Analysis Population Description

the statistical analysis was carried out by protocol (PP)

Arm/Group Title	PRO-155	Placebo
Arm/Group Description	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 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
Measure Participants	41	42
Measure eyes	69	73
Count of Units [eyes]	8	11

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-155, Placebo
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	it is considered not inferior if the differences between the groups do not exceed 20%.
Statistical Test of Hypothesis	p-Value	0.626
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Time Frame	Adverse events were monitored and recorded throughout the study, an average of 8 months.
Arm/Group Title	PRO-155		Placebo
Arm/Group Description	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 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
All Cause Mortality
	PRO-155		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/76 (0%)		0/90 (0%)
Serious Adverse Events
	PRO-155		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/76 (0%)		0/90 (0%)
Other (Not Including Serious) Adverse Events
	PRO-155		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/76 (17.1%)		19/90 (21.1%)
Eye disorders
photophobia	2/76 (2.6%)	2	4/90 (4.4%)	4
ocular burning	5/76 (6.6%)	5	5/90 (5.6%)	5
tearing	0/76 (0%)	0	1/90 (1.1%)	1
conjunctival hyperemia	3/76 (3.9%)	3	11/90 (12.2%)	11
ocular pain	0/76 (0%)	0	2/90 (2.2%)	2
Eye pruritus	0/76 (0%)	0	3/90 (3.3%)	3
Dry-eye feeling	0/76 (0%)	0	1/90 (1.1%)	1
Foreign body sensation in eyes	2/76 (2.6%)	2	3/90 (3.3%)	3
Stye	1/76 (1.3%)	1	0/90 (0%)	0
Eye irritation	0/76 (0%)	0	1/90 (1.1%)	1
Corneal epithelium defect	1/76 (1.3%)	1	0/90 (0%)	0
Gastrointestinal disorders
sickness	0/76 (0%)	0	1/90 (1.1%)	1
vomit	0/76 (0%)	0	1/90 (1.1%)	1
General disorders
sore throat	1/76 (1.3%)	1	0/90 (0%)	0
Metabolism and nutrition disorders
hypoglycemia	0/76 (0%)	0	1/90 (1.1%)	1
Nervous system disorders
Headache	1/76 (1.3%)	1	0/90 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The principal investigator can not publish any information about the investigation without prior written authorization from the atrocifier