Non-inferiority of PRO-122 Ophthalmic Solution vs KRYTANTEK Ofteno® in Glaucoma or Ocular Hypertension (CONFORTK)

• Sponsor: Laboratorios Sophia S.A de C.V. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03257813
• Collaborator: (none)
• Enrollment: 60
• Arms: 2
• Actual Duration (Months): 14.6

Study Details

Study Description

Brief Summary

Aim: To demonstrate the non-inferiority of the PRO-122 ophthalmic solution manufactured by Laboratorios Sophia S.A. de C.V. versus Krytantek Ofteno® ophthalmic solution like hypotensive therapy in subjects with primary open angle glaucoma or ocular hypertension.

Study design: a multicentric, prospective, crossover (2x2), double blind clinical study. Sample size: one hundred patients with primary open angle glaucoma or ocular hypertension. Patients in the period 1: In the first sequence 30 patients will be assigned to receive the ophthalmic solution: Krytantek Ofteno ® (timolol 0.5%%/brimonidine 0.2%/dorzolamide 2%) 1 drop B.I.D. during 30 days and the second sequence 30 patients will be assigned to receive the ophthalmic solution: PRO-122 1 drop B.I.D. during 30 days in the same period. Washout period: 20 hours. Patients in the period 2: the pharmacological intervention change to the opposite therapy for 30 days

Condition or Disease	Intervention/Treatment	Phase
Primary Open Angle Glaucoma; Ocular Hypertension	Drug: PRO-122; Drug: Krytantek Ofteno®	Phase 3

Detailed Description

The American Academy of Ophthalmology Glaucoma Panel: The primary open angle glaucoma (POAG) is a progressive, chronic optic neuropathy in adults in which intraocular pressure (IOP) and other currently unknown factors contribute to damage and in which, in the absence of other identifiable causes, there is a characteristic acquired atrophy of the optic nerve and loss of retinal ganglion cells and their axons. This condition is associated with an anterior chamber angle that is open by gonioscopic appearance.

This is a multicentric, crossover, double blind and prospective clinical study. The investigators will include patients with confirmed diagnosis of primary open-angle glaucoma or ocular hypertension, with target intraocular pressure (TIOP) within a range at which a patient is likely to remain stable or at which worsening of glaucoma will be slow enough that the risk of additional intervention is not justified.

Patients will be randomly divided into 2 groups, one of them treated with a known formulation of timolol 0.5%/brimonidine 0.2%/dorzolamide 2% (Krytantek Ofteno®, Laboratorios Sophia, Mexico) and the other one treated with PRO-122 ophthalmic solution. Patients will receive 1 drop B.I.D. into the lower conjunctival sac of either formulations and were examined at days: 1, 15, 30, 45 and 61 after initiation of treatment. A phone call security at day 75 will be performed.

Primary efficacy outcome: To evaluate the efficacy of PRO-122 versus Krytantek Ofteno® instilled onto the ocular surface in subjects with primary open angle glaucoma (POAG) or ocular hypertension (HTO), to control and maintenance of the target intraocular pressure (TIOP).

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: 60 subjects with diagnosis of open angle primary glaucoma with mild, moderate or severe damage and / or with intraocular hypertension users of Krytantek Ofteno® at least two previous months and are under control Of the corresponding IOP target. a study group A or B will be randomly assigned, in group A, therapy with Krytantek Ofteno® will be continued for 30 days, in which the subject will be evaluated again and switched from therapy to solution PRO-122 which will be used for 30 days until the 60th day, date of the final visit. In the case of those assigned to group B on day 1, the change to PRO-122 solution will be made for 30 continuous days until the date of revision on day 30, the day on which treatment with Krytantek Ofteno® will be restored to continue until the Day 60 for the final evaluation. The selected subjects will be observed for 60 days.60 subjects with diagnosis of open angle primary glaucoma with mild, moderate or severe damage and / or with intraocular hypertension users of Krytantek Ofteno® at least two previous months and are under control Of the corresponding IOP target. a study group A or B will be randomly assigned, in group A, therapy with Krytantek Ofteno® will be continued for 30 days, in which the subject will be evaluated again and switched from therapy to solution PRO-122 which will be used for 30 days until the 60th day, date of the final visit. In the case of those assigned to group B on day 1, the change to PRO-122 solution will be made for 30 continuous days until the date of revision on day 30, the day on which treatment with Krytantek Ofteno® will be restored to continue until the Day 60 for the final evaluation. The selected subjects will be observed for 60 days.
• Masking: Double (Participant, Investigator)
• Masking Description: Masking will be carried out using identical boxes in the primary package in both groups. Blinding for the research subject and the investigator will be carried out by using labels containing the assignation number, which will replace the original labels in the case of the comparator. Due to the nature of the primary containers of the research products, single-dose vials and multidose bottle, it is not possible to use identical labels.
• Primary Purpose: Treatment
• Official Title: Clinical Study to Evaluate the Non-inferiority of PRO-122 an Ophthlamic Solution Manufactured by Laboratorios Sophia, Previous Treatment With Krytantek Ofteno ®, in Subjects With Primary Open-Angle Glaucoma or Ocular Hypertension.
• Actual Study Start Date: Apr 1, 2016
• Actual Primary Completion Date: Mar 1, 2017
• Actual Study Completion Date: Jun 18, 2017

Arms and Interventions

Arm	Intervention/Treatment
Other: Group A In group A, therapy with Krytantek Ofteno® will be continued for 30 days, in which the subject will be retested and switched to a PRO-122 solution which will be used for 30 days until the 60th day, The final visit.	Drug: PRO-122; 1 drop every 12 hours for 30 days of alternating treatment with 30 days; Other Names: timolol, dorzolamide, brimonidine ; Drug: Krytantek Ofteno®; 1 drop every 12 hours for 30 days of alternating treatment with 30 days; Other Names: timolol, dorzolamide, brimonidine
Other: Group B In group B, therapy with Krytantek Ofteno® will be suspended and changes for PRO-122 for 30 days, in which the subject will be retested and later switched to Krytantek Ofteno® solution which will be used for 30 days until the 60th day, The final visit.	Drug: PRO-122; 1 drop every 12 hours for 30 days of alternating treatment with 30 days; Other Names: timolol, dorzolamide, brimonidine ; Drug: Krytantek Ofteno®; 1 drop every 12 hours for 30 days of alternating treatment with 30 days; Other Names: timolol, dorzolamide, brimonidine

Outcome Measures

Primary Outcome Measures

1. Intraocular Pressure (IOP) [Change from Baseline intraocular pressure at day 30 and 60.]

   Intraocular pressure, Unit: Millimeters of mercury (mmHg) type of variable: Continuous, Measurement method: Goldman applanation tonometry. Normal intraocular pressure 11-21 mmHg. The change between the IOP of both groups was compared (sequence 1 versus sequence 2) of the data obtained at the end of each period (day 30 and day 60).

Secondary Outcome Measures

1. Visual Acuity (VA) [Visual Acuity at Baseline (day 1) crossover visit (day 30) and final visit (day 60)]

   The VA will be evaluated basally, without refractive correction with the Snellen chart. A Snellen chart is placed at a standard distance: 20 ft. At this distance, the symbols on the line representing "normal" acuity subtend. This line, designated 20/20 is the smallest line that a person with normal acuity can read at a distance of 20fs. the scale consists of 11 lines of letters of different size, the size of the letter gives a fractional value according to the visual acuity of the patient, the value is inversely proportional to the visual acuity, if the denominator is greater the visual acuity will be less. Line 1: 20/200 Line 2: 20/100, Line 3: 20/70, line 4: 20/50, line 5: 20/40, Line 6: 20/30, line 7: 20/25, Line 8: 20/20, line 9: 20/15, line 10: 20/13, line 11: 20/10. the differences between groups in the basal, cross over and final visit will be evaluated.

Other Outcome Measures

1. Adverse Events [75 days, includes the security call]

   The presence of adverse events by percentage between groups will be evaluated. the scale is present or absent.

2. Conjunctival Hyperemia [Baseline (day 1) crossover visit (day 30) and final visit (day 60)]

   the conjunctival hyperemia will be evaluated by the presence or absence of it and the percentage of affected by group will be reported.

3. Chemosis [Baseline (day 1) crossover visit (day 30) and final visit (day 60)]

   Chemosis: qualitative ordinal variable, will be evaluated by the presence or absence of it and the percentage of affected by group will be reported.

4. Eye Burning [Baseline (day 1) crossover visit (day 30) and final visit (day 60)]

   Eye ocular burning will be evaluated by the presence or absence of it and the number of affected by group will be reported.

5. Number of Eyes With Tearing [Baseline (day 1) crossover visit (day 30) and final visit (day 60)]

   Tearing will be evaluated by the presence or absence of it and the number of affected by group will be reported

6. Number of Eyes With Foreign Body Sensation [Baseline (day 1) crossover visit (day 30) and final visit (day 60)]

   Foreign body sensation will be evaluated by the presence or absence of it and the number of affected by group will be reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18 years of age or older

• male or female.

• obtained in the external consultation.

• With diagnosis primary of open-angle glaucoma and / or hypertension classified as mild, moderate or severe glaucomatous damage, users of Krytantek Ofteno® at least two months prior to inclusion and under control of the target IOP.

• informed consent.

Exclusion Criteria:

General Criteria

1. Subjects with topical or systemic medication that interferes decisively in the results of the study. (Such as topical immunomodulators, lacrimal point tamponade, corticosteroids, ocular hypotensives other than those listed above, artificial tears with preservative).

2. Subjects (female) with an active sex life who are not using a contraceptive method.

3. Female Subjects in pregnancy or breastfeeding.

4. Female subjects with positive urine pregnancy test.

5. Positive drug addiction (verbal interrogation).

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

7. Legally or mentally disabled subjects to give informed consent for their participation in this study.

8. Subjects who can not comply with the appointments or with all the requirements of the protocol.

Ophthalmologic criteria

1. Subject with only one eye with vision.

2. Subjects with visual capacity 20/200 or worse.

3. Subjects with a narrow-angle history without treatment, with or without total or partial closure of the angle in either eye.

4. Subjects with corneal abnormalities that prevent applanation tonometry.

5. Subjects with ocular surgery or ocular trauma 6 months prior to inclusion.

6. Any ocular laser surgery 3 months prior.

7. Any uncontrolled or progressive retinal disease.

8. Inflammatory diseases of any kind.

9. Contact lens wearers.

10. Subjects with a history of hypersensitivity to any of the ingredients of the research product or its analogues.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Laboratorios Sophia S.A de C.V.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 1, 2017

More Information

Publications

None provided.

• Responsible Party: Laboratorios Sophia S.A de C.V.
• ClinicalTrials.gov Identifier: NCT03257813
• Other Study ID Numbers: SOPH122-0914/III
• First Posted: Aug 22, 2017
• Last Update Posted: Dec 9, 2019
• Last Verified: Nov 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.: timolol; dorzolamide; brimonidine; Glaucoma; Ocular hypertension
• Additional relevant MeSH terms: Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Timolol; Brimonidine Tartrate; Dorzolamide

Study Results

Participant Flow

Arm/Group Title	Group A	Group B
Arm/Group Description	In group A, therapy with Krytantek Ofteno® will be continued for 30 days, in which the subject will be retested and switched to a PRO-122 solution which will be used for 30 days until the 60th day, The final visit. PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	In group B, therapy with Krytantek Ofteno® will be suspended and changes for PRO-122 for 30 days, in which the subject will be retested and later switched to Krytantek Ofteno® solution which will be used for 30 days until the 60th day, The final visit. PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days
Period Title: Overall Study
STARTED	30	30
COMPLETED	24	27
NOT COMPLETED	6	3

Baseline Characteristics

Arm/Group Title	Group A	Group B	Total
Arm/Group Description	In group A, therapy with Krytantek Ofteno® will be continued for 30 days, in which the subject will be retested and switched to a PRO-122 solution which will be used for 30 days until the 60th day, The final visit. PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	In group B, therapy with Krytantek Ofteno® will be suspended and changes for PRO-122 for 30 days, in which the subject will be retested and later switched to Krytantek Ofteno® solution which will be used for 30 days until the 60th day, The final visit. PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	Total of all reporting groups
Overall Participants	30	30	60
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.43 (8.86)	64.37 (12.84)	66.44 (11.17)
Sex: Female, Male (Count of Participants)
Female	24 80%	21 70%	45 75%
Male	6 20%	9 30%	15 25%
Race/Ethnicity, Customized (Count of Participants)
hispanic	30 100%	30 100%	60 100%

Outcome Measures

1. Primary Outcome

Title	Intraocular Pressure (IOP)
Description	Intraocular pressure, Unit: Millimeters of mercury (mmHg) type of variable: Continuous, Measurement method: Goldman applanation tonometry. Normal intraocular pressure 11-21 mmHg. The change between the IOP of both groups was compared (sequence 1 versus sequence 2) of the data obtained at the end of each period (day 30 and day 60).
Time Frame	Change from Baseline intraocular pressure at day 30 and 60.

Outcome Measure Data

Analysis Population Description

the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.

Arm/Group Title	Sequence A	Sequence B
Arm/Group Description	First Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	First Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days
Measure Participants	30	30
Measure eyes	48	54
basal visit (day 1)	13.60 (2.9)	12.13 (1.8)
Crossover visit (day 30)	13.19 (3.2)	11.80 (2.1)
Final visit (day 60)	12.60 (3.0)	11.24 (1.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sequence A
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	it will be considered not inferior if they keep the IOP goal with differences of no more than 1.5 mmHg
Statistical Test of Hypothesis	p-Value	0.013
	Comments	Baseline
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	it will be considered not inferior if they keep the IOP goal with differences of no more than 1.5 mmHg
Statistical Test of Hypothesis	p-Value	0.001
	Comments	CrossOver
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	it will be considered not inferior if they keep the IOP goal with differences of no more than 1.5 mmHg
Statistical Test of Hypothesis	p-Value	0.050
	Comments	Final Visit
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Visual Acuity (VA)
Description	The VA will be evaluated basally, without refractive correction with the Snellen chart. A Snellen chart is placed at a standard distance: 20 ft. At this distance, the symbols on the line representing "normal" acuity subtend. This line, designated 20/20 is the smallest line that a person with normal acuity can read at a distance of 20fs. the scale consists of 11 lines of letters of different size, the size of the letter gives a fractional value according to the visual acuity of the patient, the value is inversely proportional to the visual acuity, if the denominator is greater the visual acuity will be less. Line 1: 20/200 Line 2: 20/100, Line 3: 20/70, line 4: 20/50, line 5: 20/40, Line 6: 20/30, line 7: 20/25, Line 8: 20/20, line 9: 20/15, line 10: 20/13, line 11: 20/10. the differences between groups in the basal, cross over and final visit will be evaluated.
Time Frame	Visual Acuity at Baseline (day 1) crossover visit (day 30) and final visit (day 60)

Outcome Measure Data

Analysis Population Description

the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.

Arm/Group Title	Sequence A	Sequence B
Arm/Group Description	First Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	First Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: _1 drop every 12 hours for 30 days of alternating treatment with 30 days
Measure Participants	30	30
Measure eyes	48	54
basal visit (day 1)	38.31 (3.577)	39.48 (3.742)
Crossover visit (day 30)	36.85 (3.806)	40.43 (3.753)
Final visit (day 60)	38.98 (3.717)	35.50 (3.402)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	to be considered as not inferior to the group, the differences between both should not be greater than 2 points on the snellen scale
Statistical Test of Hypothesis	p-Value	0.823
	Comments	Baseline
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	to be considered as not inferior to the group, the differences between both should not be greater than 2 points on the snellen scale
Statistical Test of Hypothesis	p-Value	0.507
	Comments	CrossOver
	Method	t-test, 2 sided
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	to be considered as not inferior to the group, the differences between both should not be greater than 2 points on the snellen scale
Statistical Test of Hypothesis	p-Value	0.495
	Comments	Final Visit
	Method	t-test, 2 sided
	Comments

3. Other Pre-specified Outcome

Title	Adverse Events
Description	The presence of adverse events by percentage between groups will be evaluated. the scale is present or absent.
Time Frame	75 days, includes the security call

Outcome Measure Data

Analysis Population Description

the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases. statistical analysis by intention to treat (ITT)

Arm/Group Title	PRO-122	Krytantek Ofteno
Arm/Group Description	all subjects who received at least one application of PRO-122 in both sequences	all subjects who received at least one application of Krytantek Ofteno in both sequences
Measure Participants	60	60
Measure eyes	120	120
mild	55.6	18.2
moderate	44.4	72.7
severe	0	9.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	to be considered as not inferior to the group, the differences between both should not be greater than 20% of the frequency.
Statistical Test of Hypothesis	p-Value	0.085
	Comments
	Method	Chi-squared
	Comments

4. Other Pre-specified Outcome

Title	Conjunctival Hyperemia
Description	the conjunctival hyperemia will be evaluated by the presence or absence of it and the percentage of affected by group will be reported.
Time Frame	Baseline (day 1) crossover visit (day 30) and final visit (day 60)

Outcome Measure Data

Analysis Population Description

the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.

Arm/Group Title	Sequence A	Sequence B
Arm/Group Description	First Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	First Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: _1 drop every 12 hours for 30 days of alternating treatment with 30 days
Measure Participants	30	30
Measure eyes	49	60
basal visit (day 1)	39.6	11.1
Crossover visit (day 30)	37.5	25.9
Final visit (day 60)	20.8	13.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	to be considered as not inferior to the group, the differences between both should not be greater than 20% of the frequency.
Statistical Test of Hypothesis	p-Value	0.001
	Comments	Baseline
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	to be considered as not inferior to the group, the differences between both should not be greater than 20% of the frequency.
Statistical Test of Hypothesis	p-Value	0.148
	Comments	CrossOver
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	to be considered as not inferior to the group, the differences between both should not be greater than 20% of the frequency.
Statistical Test of Hypothesis	p-Value	0.212
	Comments	Final Visit
	Method	Fisher Exact
	Comments

5. Other Pre-specified Outcome

Title	Chemosis
Description	Chemosis: qualitative ordinal variable, will be evaluated by the presence or absence of it and the percentage of affected by group will be reported.
Time Frame	Baseline (day 1) crossover visit (day 30) and final visit (day 60)

Outcome Measure Data

Analysis Population Description

the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.

Arm/Group Title	Sequence A	Sequence B
Arm/Group Description	First Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	First Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: _1 drop every 12 hours for 30 days of alternating treatment with 30 days
Measure Participants	30	30
Measure eyes	49	50
basal visit (day 1)	0	3.7
Crossover visit (day 30)	0	3.7
Final visit (day 60)	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	to be considered as not inferior to the group, the differences between both should not be greater than 20% of the frequency.
Statistical Test of Hypothesis	p-Value	0.497
	Comments	Baseline
	Method	Chi-squared, Corrected
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	to be considered as not inferior to the group, the differences between both should not be greater than 20% of the frequency.
Statistical Test of Hypothesis	p-Value	0.497
	Comments	CrossOver
	Method	Chi-squared, Corrected
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	to be considered as not inferior to the group, the differences between both should not be greater than 20% of the frequency.
Statistical Test of Hypothesis	p-Value	0
	Comments	Final Visit No statistic will be calculated because Final Chemosis is a constant
	Method	Chi-squared, Corrected
	Comments

6. Other Pre-specified Outcome

Title	Eye Burning
Description	Eye ocular burning will be evaluated by the presence or absence of it and the number of affected by group will be reported.
Time Frame	Baseline (day 1) crossover visit (day 30) and final visit (day 60)

Outcome Measure Data

Analysis Population Description

the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.

Arm/Group Title	Sequence A	Sequence B
Arm/Group Description	First Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	First Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: _1 drop every 12 hours for 30 days of alternating treatment with 30 days
Measure Participants	30	30
Measure eyes	49	50
basal visit (day 1)	16	18
Crossover visit (day 30)	12	18
Final visit (day 60)	14	19

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	to be considered as not inferior to the group, the differences between both should not be greater than 20% of the frequency.
Statistical Test of Hypothesis	p-Value	1.000
	Comments	baseline
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	to be considered as not inferior to the group, the differences between both should not be greater than 20% of the frequency.
Statistical Test of Hypothesis	p-Value	0.391
	Comments	Cross Over
	Method	Chi-squared
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	to be considered as not inferior to the group, the differences between both should not be greater than 20% of the frequency.
Statistical Test of Hypothesis	p-Value	0.534
	Comments	Final Visit
	Method	Chi-squared
	Comments

7. Other Pre-specified Outcome

Title	Number of Eyes With Tearing
Description	Tearing will be evaluated by the presence or absence of it and the number of affected by group will be reported
Time Frame	Baseline (day 1) crossover visit (day 30) and final visit (day 60)

Outcome Measure Data

Analysis Population Description

the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.

Arm/Group Title	Sequence A	Sequence B
Arm/Group Description	First Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	First Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: _1 drop every 12 hours for 30 days of alternating treatment with 30 days
Measure Participants	30	30
Measure eyes	49	50
basal visit (day 1)	9	2
Crossover visit (day 30)	8	9
Final visit (day 60)	7	9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	to be considered as not inferior to the group, the differences between both should not be greater than 20% of the frequency.
Statistical Test of Hypothesis	p-Value	0.023
	Comments	Baseline
	Method	Chi-squared, Corrected
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	to be considered as not inferior to the group, the differences between both should not be greater than 20% of the frequency.
Statistical Test of Hypothesis	p-Value	1.000
	Comments	CrossOver
	Method	Chi-squared
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	to be considered as not inferior to the group, the differences between both should not be greater than 20% of the frequency.
Statistical Test of Hypothesis	p-Value	0.793
	Comments	Final Visit
	Method	Chi-squared
	Comments

8. Other Pre-specified Outcome

Title	Number of Eyes With Foreign Body Sensation
Description	Foreign body sensation will be evaluated by the presence or absence of it and the number of affected by group will be reported.
Time Frame	Baseline (day 1) crossover visit (day 30) and final visit (day 60)

Outcome Measure Data

Analysis Population Description

the statistical analysis was carried out taking into account each eye as a case number, therefore, each research subject could provide 2 cases.

Arm/Group Title	Sequence A	Sequence B
Arm/Group Description	First Period: PRO-122: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days	First Period: Krytantek Ofteno®: 1 drop every 12 hours for 30 days of alternating treatment with 30 days Second Period: _1 drop every 12 hours for 30 days of alternating treatment with 30 days
Measure Participants	30	30
Measure eyes	49	50
basal visit (day 1)	14	14
Crossover visit (day 30)	14	16
Final visit (day 60)	5	7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	to be considered as not inferior to the group, the differences between both should not be greater than 20% of the frequency.
Statistical Test of Hypothesis	p-Value	0.825
	Comments	Baseline
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	to be considered as not inferior to the group, the differences between both should not be greater than 20% of the frequency.
Statistical Test of Hypothesis	p-Value	1.000
	Comments	CrossOver
	Method	Chi-squared
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Sequence A, Sequence B
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	to be considered as not inferior to the group, the differences between both should not be greater than 20% of the frequency.
Statistical Test of Hypothesis	p-Value	0.765
	Comments
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	2 months
Adverse Event Reporting Description	The study's e-CRF was designed to collect adverse events for each research product separately. The sequence or crossing of the products under investigation was not considered for the report of adverse events because it can be detected at what time the event occurs and directly link it to the product that was being administered at the same time.
Arm/Group Title	PRO-122		Krytantek Ofteno®
Arm/Group Description	All adverse events that occurred with the product under investigation PRO-122 were collected regardless of the sequence in which they participated. The 30 participants of both sequences received at least one dose of PRO-122, therefore 60 subjects exposed in this group are considered.		All adverse events that occurred with the product under investigation Krytantek Ofteno® were collected regardless of the sequence in which they participated. The 30 participants of both sequences received at least one dose of Krytantek Ofteno®, therefore 60 subjects exposed in this group are considered.
All Cause Mortality
	PRO-122		Krytantek Ofteno®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		0/60 (0%)
Serious Adverse Events
	PRO-122		Krytantek Ofteno®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/60 (0%)		1/60 (1.7%)
Gastrointestinal disorders
acute gastritis	0/60 (0%)	0	1/60 (1.7%)	1
Other (Not Including Serious) Adverse Events
	PRO-122		Krytantek Ofteno®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/60 (20%)		08/60 (13.3%)
Cardiac disorders
sinus bradycardia	0/60 (0%)	0	1/60 (1.7%)	1
Ear and labyrinth disorders
vertigo	1/60 (1.7%)	1	0/60 (0%)	0
Eye disorders
allergic Blepharokeratoconjunctivitis	2/60 (3.3%)	2	0/60 (0%)	0
bacterial conjunctivitis	1/60 (1.7%)	1	1/60 (1.7%)	1
Dotted Keratopathy	0/60 (0%)	0	3/60 (5%)	3
Gastrointestinal disorders
pharyngitis tonsillitis	2/60 (3.3%)	2	1/60 (1.7%)	1
stomach flu	1/60 (1.7%)	1	0/60 (0%)	0
intestinal amebiasis	0/60 (0%)	0	1/60 (1.7%)	1
peptic acid disease	0/60 (0%)	0	1/60 (1.7%)	1
General disorders
headache	2/60 (3.3%)	2	0/60 (0%)	0
Meniere syndrome exacerbated	1/60 (1.7%)	1	0/60 (0%)	0
Musculoskeletal and connective tissue disorders
maxillary traumatism	1/60 (1.7%)	1	0/60 (0%)	0
ankle pain	1/60 (1.7%)	1	0/60 (0%)	0
low back pain	1/60 (1.7%)	1	0/60 (0%)	0
Respiratory, thoracic and mediastinal disorders
rhinopharyngitis	4/60 (6.7%)	4	1/60 (1.7%)	1
Skin and subcutaneous tissue disorders
atopic dermatitis	0/60 (0%)	0	1/60 (1.7%)	1
atopic dermatitis	1/60 (1.7%)	1	0/60 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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