PRO-122/I: Safety and Tolerability of the Preservative-free Ophthalmic Solution PRO-122 Compared With Krytantek Ofteno®

• Sponsor: Laboratorios Sophia S.A de C.V. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03966365
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Actual Duration (Months): 3.9
• Patients Per Site Per Month: 6.1

Study Details

Study Description

Brief Summary

Therapeutic indication: Ocular hypotensive Use: Primary open-angle glaucoma and ocular hypertension.

Objectives: To evaluate the safety and tolerability of the preservative-free formulation PRO-122 manufactured by Sophia Laboratories, S.A. of C.V. on the ocular surface of clinically healthy subjects.

Hypothesis: The ophthalmic solution PRO-122 presents a profile of safety and tolerability similar to Krytantek Ofteno®, in healthy subjects.

Methodology: Phase I clinical trial, controlled, parallel group, double blind, randomized.

Number of patients: n=24 12 subjects per group (both eyes). Main inclusion criteria:Clinically healthy subjects.

Condition or Disease	Intervention/Treatment	Phase
Glaucoma	Drug: PRO-122; Drug: Krytantek Ofteno®	Phase 1

Detailed Description

Number of patients: n = 24 12 subjects per group (both eyes). Main inclusion criteria:

Clinically healthy subjects.

Treatment duration: 7 days. Duration of subject in the study: 15 to 22 days.

Adverse events will be reported and cataloged based on the MedDRA dictionary and will be reported to the corresponding regulatory entity.

The sponsor will carry out monitoring or quality visits to the research sites where it corroborates the information of the source documents and will contrast them with the information presented in the electronic CRF. Electronic case report forms will be evaluated by the clinical research associate and the clinical team of the sponsor (medical ophthalmologist researcher and pharmacologist of clinical safety).

Statistical methodology:

The data will be expressed with measures of central tendency: mean and standard deviation for the quantitative variables. The qualitative variables will be presented in frequencies and percentages. The statistical analysis will be carried out by means of the Mann-Whitney U test for the quantitative variables for the difference between the groups. The difference between the qualitative variables will be analyzed by means of X2 (Chi2). An alpha ≤ 0.05 will be considered significant.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Phase I clinical trial, controlled, parallel group, double blind, randomized.Phase I clinical trial, controlled, parallel group, double blind, randomized.
• Masking: Double (Investigator, Outcomes Assessor)
• Masking Description: Blinding will correspond to the principal investigator and coinvestigator. In addition, the statistical analysis will be carried out in a blinded manner for the final analysis. Blinding can not be guaranteed in the subject. The masking will be done through the secondary container. The primary packaging will not be masked by the morphological difference between them. The sponsor and the research center will have two blind / non-blind teams. They will be identified by means of identical labels. Which, in accordance with current and applicable regulations, must contain at least: Name, address and telephone number of the sponsor. Pharmaceutical form and route of administration. Lot Number. Caption "Exclusively for clinical studies" Date of Expiry
• Primary Purpose: Treatment
• Official Title: Phase I Clinical Study, to Evaluate the Safety and Tolerability of the Preservative-free Ophthalmic Solution PRO-122 Compared With Krytantek Ofteno®, Elaborated by Sophia Laboratories, S.A. of C.V. on the Ocular Surface of Ophthalmologically and Clinically Healthy Subjects
• Actual Study Start Date: May 2, 2019
• Actual Primary Completion Date: Aug 30, 2019
• Actual Study Completion Date: Aug 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PRO-122 - Dosage: 1 drop every 12 hours, in both eyes	Drug: PRO-122; PRO-122. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution free of preservatives. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. Route of administration: topical ophthalmic.; Other Names: timolol 0.5% brimonidine 0.2% dorzolamide 2% Krytantek PF Krytantek Ofteno® Preservative Free
Active Comparator: Krytantek Ofteno® - Dosage: 1 drop every 12 hours, in both eyes	Drug: Krytantek Ofteno®; - 1. Krytantek Ofteno®. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - Route of administration: topical ophthalmic.; Other Names: timolol 0.5% brimonidine 0.2% dorzolamide 2%

Outcome Measures

Primary Outcome Measures

1. Number of Adverse Events [during the 14 days of evaluation, including the safety call (day 14)]

   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. it will be evaluated by the number of reported cases per group.

2. Eye Comfort Index [will be evaluated at the end of the treatment, at the final visit (day 8)]

   It is a questionnaire designed to measure the irritation of the ocular surface with Rasch analysis to produce estimates on a linear scale of intervals (ratings: 0-100).The Eye comfort index contains items that focus on the discomfort associated with alterations of the ocular surface. Values closer or equal to one hundred (100) correspond to greater discomfort, while values closer or equal to zero (0) correspond to greater comfort.

Secondary Outcome Measures

1. Number of Eyes With Epithelial Defects by Grade [will be evaluated at the end of the treatment, at the final visit (day 8)]

   The epithelial defects will be evaluated by means of two stains, green lissamine 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. Visual Ability [will be evaluated at the end of the treatment, at the final visit (day 8)]

   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 or 1.0 in decimal and the worst 20/200 or 0.1 in decimal number. For the appropriate management of the data, the result of the fraction obtained from the snellen scale is transformed to decimals, in this case subjects close to or equal to 1.0 have better visual acuity while subjects close to or equal to 0.1 have worse visual acuity. The decimal equivalence scale is the result of the division of the fraction obtained in the Snellen chart. where 20/20 = 1.0; Do not confuse with Logmar scale where 20/20 = 0.0 Equivalences Snellen Scale = decimals: 20/200=0.1, 20/100=0.2, 20/50=0.4, 20/40=0.5, 20/30=0.66, 20/25=0.8, 20/20=1.0, etc.

3. Participants With Conjunctival Hyperemia (CH) by Grade [will be evaluated at the end of the treatment, at the final visit (day 8)]

   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.

4. Participants With Chemosis [will be evaluated at the end of the treatment, at the final visit (day 8)]

   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.

Other Outcome Measures

1. Changes in Intraocular Pressure [will be evaluated at the end of the treatment, at the final visit (day 8)]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• • Clinically healthy

• Ability to give your signed informed consent, and show willingness to comply with study procedures and to modify your lifestyle activities (Section 6.2.2)

• Age between 18 to 45 years.

• Indistinct sex.

• Women must ensure a hormonal contraceptive method or intrauterine device during the study period.

• Blood tests: within normal parameters or with a range of ± 20% as long as the subject is clinically healthy.

• Blood count (BH): Hemoglobin, erythrocytes, hematocrit, total leukocytes, platelets, mean corpuscular volume and mean corpuscular hemoglobin.

• Blood chemistry of three elements (QS): Glucose, urea and creatinine.

• Liver function tests (PFH): Aspartate Aminotransferase and Alanine Aminotransferase, total bilirubin, direct and indirect.

• Visual ability 20/30 or better in both eyes.

• Vital signs within normal parameters.

• Intraocular pressure ≥10 and ≤ 21 mmHg.

Exclusion Criteria:

• Users of topical ophthalmic products of any kind.

• Users of medicines, or herbal products, by any other route of administration, with the exception of hormonal contraceptives in the case of women.

• Women who are pregnant or breastfeeding.

• Participation in clinical research studies 90 days prior to inclusion in the present study.

• Previous participation in this same study.

• Users of contact lenses.

• History of any chronic-degenerative disease.

• Inflammatory or infectious disease, active at the time of study entry.

• Injuries or traumatisms not resolved at the time of admission to the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Unidad Clínica de Bioequivalencia, S. de R.L. de C.V.	Guadalajara	Jalisco	Mexico	44190

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 - May 22, 2018

More Information

Publications

None provided.

• Responsible Party: Laboratorios Sophia S.A de C.V.
• ClinicalTrials.gov Identifier: NCT03966365
• Other Study ID Numbers: SOPH122-0518/I
• First Posted: May 29, 2019
• Last Update Posted: Dec 13, 2019
• Last Verified: Dec 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.: Glaucoma; Krytantek; Krytantek PF; PRO-122
• Additional relevant MeSH terms: Glaucoma; Timolol; Brimonidine Tartrate; Dorzolamide

Study Results

Participant Flow

Arm/Group Title	PRO-122	Krytantek Ofteno®
Arm/Group Description	- Dosage: 1 drop every 12 hours, in both eyes PRO-122: - PRO-122. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution free of preservatives. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - Route of administration: topical ophthalmic.	- Dosage: 1 drop every 12 hours, in both eyes Krytantek Ofteno®: - - 1. Krytantek Ofteno®. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - - Route of administration: topical ophthalmic.
Period Title: Overall Study
STARTED	12	12
COMPLETED	11	12
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	PRO-122	Krytantek Ofteno®	Total
Arm/Group Description	- Dosage: 1 drop every 12 hours, in both eyes PRO-122: - PRO-122. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution free of preservatives. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - Route of administration: topical ophthalmic.	- Dosage: 1 drop every 12 hours, in both eyes Krytantek Ofteno®: - - 1. Krytantek Ofteno®. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - - Route of administration: topical ophthalmic.	Total of all reporting groups
Overall Participants	12	12	24
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	25.1 (4.8)	27.6 (6.8)	26.3 (5.3)
Sex: Female, Male (Count of Participants)
Female	5 41.7%	6 50%	11 45.8%
Male	7 58.3%	6 50%	13 54.2%
Race/Ethnicity, Customized (Count of Participants)
Latin	12 100%	12 100%	24 100%
Region of Enrollment (Count of Participants)
Mexico	12 100%	12 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Number of Adverse Events
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. it will be evaluated by the number of reported cases per group.
Time Frame	during the 14 days of evaluation, including the safety call (day 14)

Outcome Measure Data

Analysis Population Description

The statistical analysis was by intention to treat (ITT)

Arm/Group Title	PRO-122	Krytantek Ofteno®
Arm/Group Description	- Dosage: 1 drop every 12 hours, in both eyes PRO-122: - PRO-122. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution free of preservatives. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - Route of administration: topical ophthalmic.	- Dosage: 1 drop every 12 hours, in both eyes Krytantek Ofteno®: - - 1. Krytantek Ofteno®. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - - Route of administration: topical ophthalmic.
Measure Participants	12	12
Number [adverse events]	28	31

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-122, Krytantek Ofteno®
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.706
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Primary Outcome

Title	Eye Comfort Index
Description	It is a questionnaire designed to measure the irritation of the ocular surface with Rasch analysis to produce estimates on a linear scale of intervals (ratings: 0-100).The Eye comfort index contains items that focus on the discomfort associated with alterations of the ocular surface. Values closer or equal to one hundred (100) correspond to greater discomfort, while values closer or equal to zero (0) correspond to greater comfort.
Time Frame	will be evaluated at the end of the treatment, at the final visit (day 8)

Outcome Measure Data

Analysis Population Description

Analysis per protocol (PP)

Arm/Group Title	PRO-122	Krytantek Ofteno®
Arm/Group Description	- Dosage: 1 drop every 12 hours, in both eyes PRO-122: - PRO-122. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution free of preservatives. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - Route of administration: topical ophthalmic.	- Dosage: 1 drop every 12 hours, in both eyes Krytantek Ofteno®: - - 1. Krytantek Ofteno®. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - - Route of administration: topical ophthalmic.
Measure Participants	12	12
Mean (Standard Deviation) [units on a scale]	24.6 (12.6)	27.0 (12.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-122, Krytantek Ofteno®
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.622
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Number of Eyes With Epithelial Defects by Grade
Description	The epithelial defects will be evaluated by means of two stains, green lissamine 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 8)

Outcome Measure Data

Analysis Population Description

The statistical analysis was per protocol (PP)

Arm/Group Title	PRO-122	Krytantek Ofteno®
Arm/Group Description	- Dosage: 1 drop every 12 hours, in both eyes PRO-122: - PRO-122. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution free of preservatives. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - Route of administration: topical ophthalmic.	- Dosage: 1 drop every 12 hours, in both eyes Krytantek Ofteno®: - - 1. Krytantek Ofteno®. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - - Route of administration: topical ophthalmic.
Measure Participants	11	12
Measure eyes	22	24
Green lissamine grade 0	20	16
Green lissamine grade 1	2	4
Green lissamine grade 2	0	4
Green lissamine grade 3	0	0
Green lissamine grade 4	0	0
Fluorescein grade 0	22	22
Fluorescein grade 1	0	2
Fluorescein grade 2	0	0
Fluorescein grade 3	0	0
Fluorescein grade 4	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-122, Krytantek Ofteno®
	Comments	Green lissamine treatment groups
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.081
	Comments
	Method	Chi-squared, Corrected
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PRO-122, Krytantek Ofteno®
	Comments	Fluorescein treatment groups
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.490
	Comments
	Method	Chi-squared, Corrected
	Comments

4. Secondary Outcome

Title	Visual Ability
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 or 1.0 in decimal and the worst 20/200 or 0.1 in decimal number. For the appropriate management of the data, the result of the fraction obtained from the snellen scale is transformed to decimals, in this case subjects close to or equal to 1.0 have better visual acuity while subjects close to or equal to 0.1 have worse visual acuity. The decimal equivalence scale is the result of the division of the fraction obtained in the Snellen chart. where 20/20 = 1.0; Do not confuse with Logmar scale where 20/20 = 0.0 Equivalences Snellen Scale = decimals: 20/200=0.1, 20/100=0.2, 20/50=0.4, 20/40=0.5, 20/30=0.66, 20/25=0.8, 20/20=1.0, etc.
Time Frame	will be evaluated at the end of the treatment, at the final visit (day 8)

Outcome Measure Data

Analysis Population Description

the statistical analysis was per protocol (PP)

Arm/Group Title	PRO-122	Krytantek Ofteno®
Arm/Group Description	- Dosage: 1 drop every 12 hours, in both eyes PRO-122: - PRO-122. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution free of preservatives. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - Route of administration: topical ophthalmic.	- Dosage: 1 drop every 12 hours, in both eyes Krytantek Ofteno®: - - 1. Krytantek Ofteno®. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - - Route of administration: topical ophthalmic.
Measure Participants	11	12
Mean (Standard Deviation) [Decimal score]	0.949 (0.11)	0.907 (0.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-122, Krytantek Ofteno®
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.253
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Participants With Conjunctival Hyperemia (CH) by Grade
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 8)

Outcome Measure Data

Analysis Population Description

the analysis was per protocol

Arm/Group Title	PRO-122	Krytantek Ofteno®
Arm/Group Description	- Dosage: 1 drop every 12 hours, in both eyes PRO-122: - PRO-122. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution free of preservatives. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - Route of administration: topical ophthalmic.	- Dosage: 1 drop every 12 hours, in both eyes Krytantek Ofteno®: - - 1. Krytantek Ofteno®. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - - Route of administration: topical ophthalmic.
Measure Participants	11	12
Normal (0)	10 83.3%	9 75%
Very mild (1)	0 0%	3 25%
Mild (2)	1 8.3%	0 0%
Moderate (3)	0 0%	0 0%
Severe (4)	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-122, Krytantek Ofteno®
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.031
	Comments
	Method	Chi-squared, Corrected
	Comments

6. Secondary Outcome

Title	Participants With Chemosis
Description	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 8)

Outcome Measure Data

Analysis Population Description

the analysis was per protocol

Arm/Group Title	PRO-122	Krytantek Ofteno®
Arm/Group Description	- Dosage: 1 drop every 12 hours, in both eyes PRO-122: - PRO-122. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution free of preservatives. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - Route of administration: topical ophthalmic.	- Dosage: 1 drop every 12 hours, in both eyes Krytantek Ofteno®: - - 1. Krytantek Ofteno®. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - - Route of administration: topical ophthalmic.
Measure Participants	11	12
Count of Participants [Participants]	0 0%	0 0%

7. Other Pre-specified Outcome

Title	Changes in Intraocular Pressure
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 8)

Outcome Measure Data

Analysis Population Description

the analysis was per protocol

Arm/Group Title	PRO-122	Krytantek Ofteno®
Arm/Group Description	- Dosage: 1 drop every 12 hours, in both eyes PRO-122: - PRO-122. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution free of preservatives. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - Route of administration: topical ophthalmic.	- Dosage: 1 drop every 12 hours, in both eyes Krytantek Ofteno®: - - 1. Krytantek Ofteno®. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - - Route of administration: topical ophthalmic.
Measure Participants	11	12
Mean (Standard Deviation) [mmHg]	12.32 (2.3)	11.78 (1.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-122, Krytantek Ofteno®
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.651
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	Adverse events were monitored throughout the study, which lasted about 4 months.
Arm/Group Title	PRO-122		Krytantek Ofteno®
Arm/Group Description	- Dosage: 1 drop every 12 hours, in both eyes PRO-122: - PRO-122. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution free of preservatives. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - Route of administration: topical ophthalmic.		- Dosage: 1 drop every 12 hours, in both eyes Krytantek Ofteno®: - - 1. Krytantek Ofteno®. Timolol 0.5% / brimonidine 0.2% / dorzolamide 2% ophthalmic solution. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. - - Route of administration: topical ophthalmic.
All Cause Mortality
	PRO-122		Krytantek Ofteno®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Serious Adverse Events
	PRO-122		Krytantek Ofteno®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	PRO-122		Krytantek Ofteno®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/12 (91.7%)		11/12 (91.7%)
Ear and labyrinth disorders
clogged ear	1/12 (8.3%)	1	0/12 (0%)	0
earache	0/12 (0%)	0	1/12 (8.3%)	1
Eye disorders
ocular burning	11/12 (91.7%)	11	11/12 (91.7%)	11
nonspecific conjunctivitis	0/12 (0%)	0	1/12 (8.3%)	1
pruritus	1/12 (8.3%)	1	2/12 (16.7%)	2
ocular hyperemia	2/12 (16.7%)	2	2/12 (16.7%)	2
feeling of sticky eyes	0/12 (0%)	0	1/12 (8.3%)	1
decreased visual acuity	1/12 (8.3%)	1	0/12 (0%)	0
foreign body sensation in eye	0/12 (0%)	0	2/12 (16.7%)	2
Dry Eye	2/12 (16.7%)	2	1/12 (8.3%)	1
eyestrain	0/12 (0%)	0	3/12 (25%)	3
tearing	0/12 (0%)	0	2/12 (16.7%)	2
Gastrointestinal disorders
stomach ache	0/12 (0%)	0	1/12 (8.3%)	1
dysgeusia	4/12 (33.3%)	4	0/12 (0%)	0
dizziness	1/12 (8.3%)	1	0/12 (0%)	0
Nervous system disorders
headache	2/12 (16.7%)	2	1/12 (8.3%)	1
Respiratory, thoracic and mediastinal disorders
rhinitis	1/12 (8.3%)	1	0/12 (0%)	0
Skin and subcutaneous tissue disorders
herpes labialis	1/12 (8.3%)	1	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

only the sponsor has the decision to disseminate or publish the information obtained from the investigation and the PIs involved must submit a formal request to the sponsor if they are willing to disseminate or publish such information, they may only publish them if they have the written authorization of the sponsor (Laboratoios Sophia S.A. de C.V.).