Efficacy and Safety of the Ophthalmic Solution PRO-087 Versus Systane ® Ultra and Ultra Preservative Free (087LATAMFIV)

• Sponsor: Laboratorios Sophia S.A de C.V. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03223909
• Collaborator: (none)
• Enrollment: 326
• Location: 1
• Arms: 3
• Actual Duration (Months): 26.1
• Patients Per Site Per Month: 12.5

Study Details

Study Description

Brief Summary

Efficacy and Safety of the Ophthalmic Solution PRO-087 versus Systane ® Ultra and Systane ® Ultra Preservative Free on the Tear Film Dysfunction Syndrome from Mild to Moderate Clinical trial To evaluate the effectiveness of preservative-free ophthalmic formulation PRO-087 (by Laboratorios Sophia, S.A. de C.V.) to restore the anatomical and physiological characteristics of the ocular surface, as well as its distribution and the characteristics of the mild to moderate tear film dysfunction syndrome compared to Systane ® Ultra and Ultra Systane ® preservative free (by Laboratorios Alcon, S.A. de C.V.).

Controlled, randomized, double-blind, masked clinical study, comparing the safety and efficacy of preservative-free PR0-087 vs Systane Ultra with preservative and Systane Ultra preservative free, in subjects with mild to moderate tear film dysfunction syndrome, for a period of 90 days plus 15 days of remote surveillance, in which one of the three agents will be administered (PR0-087, Systane® Ultra or Systane® Ultra preservative free) with a q.i.d. dosage. in both eyes, with regular follow-up visits (5 overall).

Best-corrected visual acuity Intraocular pressure Ocular surface Anterior segment examination Posterior segment examination Tear film break-up time Schirmer test Corneal epithelization Goblet cells count Adverse events Subjects with a clinical diagnosis of mild to moderate tear film dysfunction syndrome between 18 and 90 years old, without concomitant eye diseases nor requiring different treatments of any of the three interventions in this study They will be randomized in 3 groups where PRO-087, Systane® Ultra o Systane® Ultra preservative free will be administered.

Condition or Disease	Intervention/Treatment	Phase
Dry Eye Syndrome	Drug: PRO-087; Drug: Systane Ultra; Drug: Systane Ultra Preservative Free	Phase 4

Detailed Description

Design Controlled, double-blind, randomized, clinical trial comparing the safety and efficacy parameters between a group of subjects with a diagnose of mild to moderate tear film dysfunction syndrome under a regimen of ophthalmic solution lubricant drops PRO-087 versus subject under Systane® Ultra or Systane® Ultra preservative free, with the same diagnosis, with a follow-up of 90 days

MAIN OBJECTIVE:

To evaluate the effectiveness of preservative-free ophthalmic formulation PRO-087 (by Laboratorios Sophia, S.A. de C.V.) to restore the anatomical and physiological characteristics of the ocular surface, as well as its distribution and the characteristics of the mild to moderate tear film dysfunction syndrome compared to Systane ® Ultra and Ultra Systane ® preservative free (by Laboratorios Alcon, S.A. de C.V.).

SPECIFIC OBJECTIVES:

To evaluate the safety of the preservative-free ophthalmic formulation PRO-087 (by Laboratorios Sophia, S.A. de C.V.) on the corneal and conjunctival epithelium, intraocular pressure, and structures of anterior and posterior segment in patients with tear film dysfunction syndrome from mild to moderate.

To determine the correlation between improvement of clinical status and perceived improvement of symptoms of each participant in each study group.

To compare the qualitative and quantitative histological status of the ocular surface before and after the pharmacological intervention in each study group to determine the evolution under the intervention of PRO-087.

To evaluate the quantitative rating of tear film production by the Schirmer Test throughout the study.

To qualitatively assess the tear film production by measuring the tear film break-up time stained with fluorescein and cobalt filter.

Blinding:

The double-blind study is a procedure in which the patient and the treating doctor ignore to which intervention group the study patient was assigned. To achieve the blinding of both the drug in research and both comparator drugs, these will be labeled in the same way (masking). Besides the figure of an unblinded pharmacist, who is responsible for the delivery of the medication to the patient, will be added. Blinding codes are protected by an outsider appointed by the study sponsor. The codes are also available in the research center (fully sealed), so that they can be consulted by the investigator in case a subject presents a serious adverse event, prior authorization from the study sponsor; the blinding also continues rigorous during the data analysis and interpretation.

patients with tear film dysfunction, classified as mild to moderate, will be included and randomized into 3 groups; the first being treated with PRO-087 ophthalmic solution, the second with Systane® Ultra ophthalmic solution, and the third with ophthalmic solution Systane® Ultra preservative free.

Pharmacological Intervention

The pharmacological intervention will be the instillation of the ophthalmic solution in the bottom of the conjunctival sac during the waking period, in any of the following study groups:

1. Preservative free PRO-087 ophthalmic solution. Dropper bottle. Multidose 1 drop every 4 hours for 90 days.

2. Systane® Ultra ophthalmic solution. Dropper bottle. Multidose. 1 drop every 4 hours for 90 days.

3. Systane ® Ultra preservative free ophthalmic solution. Single-use vials. 1 drop every 4 hours for 90 days.

Study Design

• Study Type: Interventional
• Actual Enrollment: 326 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Controlled, double-blind, randomized, clinical trial comparing the safety and efficacy parameters between a group of subjects with a diagnose of mild to moderate tear film dysfunction syndrome under a regimen of ophthalmic solution lubricant drops PRO-087 versus subject under Systane® Ultra or Systane® Ultra preservative free, with the same diagnosis, with a follow-up of 90 days.Controlled, double-blind, randomized, clinical trial comparing the safety and efficacy parameters between a group of subjects with a diagnose of mild to moderate tear film dysfunction syndrome under a regimen of ophthalmic solution lubricant drops PRO-087 versus subject under Systane® Ultra or Systane® Ultra preservative free, with the same diagnosis, with a follow-up of 90 days.
• Masking: Double (Participant, Investigator)
• Masking Description: The double-blind study is a procedure in which the patient and the treating doctor ignore to which intervention group the study patient was assigned. To achieve the blinding of both the drug in research and both comparator drugs, these will be labeled in the same way (masking). Besides the figure of an unblinded pharmacist, who is responsible for the delivery of the medication to the patient, will be added. Blinding codes are protected by an outsider appointed by the study sponsor. The codes are also available in the research center (fully sealed), so that they can be consulted by the investigator in case a subject presents a serious adverse event, prior authorization from the study sponsor; the blinding also continues rigorous during the data analysis and interpretation.
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of the Ophthalmic Solution PRO-087 Versus Systane ® Ultra and Systane ® Ultra Preservative Free on Tear Film Dysfunction Syndrome From Mild to Moderate
• Actual Study Start Date: Oct 13, 2016
• Actual Primary Completion Date: Oct 16, 2018
• Actual Study Completion Date: Dec 16, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PRO-087 PF Preservative free (PF) PRO-087 ophthalmic solution. Dropper bottle. Multidose 1 drop every 4 hours for 90 days.	Drug: PRO-087; 0.1% sodium hyaluronate, free-preservative 0.18% chondroitin sulphate; Other Names: Chondroitin sulfate sodium hyaluronate
Active Comparator: Systane Ultra Systane Ultra ophthalmic solution, Dropper bottle, Multidose. 1 drop every 4 hours for 90 days.	Drug: Systane Ultra; Is a sterile solution containing polyethylene glycol 400, propylene glycol, hydroxypropyl-guar, sorbitol, aminomethylpropanol, boric acid, potassium chloride, sodium chloride and POLYQUAD® (poly-hydronium chloride) 0.001% as preservative.; Other Names: polyethylene glycol 400, propylene glycol
Active Comparator: Systane Ultra PF Systane Ultra, preservative free ophthalmic solution, single-use vials. 1 drop every 4 hours for 90 days.	Drug: Systane Ultra Preservative Free; Polyethylene Glycol 400 0.4%Lubricant, Propylene Glycol 0.3% Lubricant,; Other Names: Polyethylene Glycol 400 0.4%, Propylene Glycol 0.3%

Outcome Measures

Primary Outcome Measures

1. Visual Acuity [Change from Baseline visual acuity at 90 days]

   Best-corrected visual acuity

Secondary Outcome Measures

1. Corneal Epithelization Defects With Rose of Bengal [Final Visit (day 90)]

   Percentage of the damaged epithelium of the ocular surface, reduction of staining according to the oxford scale.

2. Tear Film Break-up Time (TBUT) [Base line and Final Visit (day 90)]

   Tear breakup time (TBUT) is a clinical test used to assess for evaporative dry eye disease. To measure TBUT, fluorescein is instilled into the patient's tear film and the patient is asked not to blink while the tear film is observed under a broad beam of cobalt blue illumination. The TBUT is recorded as the number of seconds that elapse between the last blink and the appearance of the first dry spot in the tear film, as seen in this progression of these slit lamps photos over time. A TBUT under 10 seconds is considered abnormal

3. Schirmer Test [Base line and Final Visit (day 90)]

   Schirmer's test determines whether the eye produces enough tears to keep it moist. This test is used when a person experiences very dry eyes or excessive watering of the eyes. It poses no risk to the subject. A negative (more than 10 mm of moisture on the filter paper in 5 minutes) test result is normal. Both eyes normally secrete the same amount of tears.

4. Adverse Events [90 days]

   Presence of adverse events modifying some of the abovementioned criteria or others, evaluated as serious.

5. Ocular Surface Disease Index (OSDI) [Change from Baseline OSDI at 90 days]

   The OSDI, which was created to order to quickly assess the symptoms of ocular irritation in dry eye disease and how they affect functioning related to vision. This 12-item questionnaire assesses dry eye symptoms and the effects it has on vision-related function in the past of the patient's life. The questionnaire has 3 subscales: ocular symptoms, vision-related function, and environmental triggers. Patients rate their responses on a 0 to 4 scale with 0 corresponding to "none of the time" and 4 corresponding to "all of the time." A final score is calculated which ranges from 0 to 100 with scores 0 to 12 representing normal, 13 to 22 representing mild dry eye disease, 23 to 32 representing moderate dry eye disease, and greater than 33 representing severe dry eye disease.

6. Goblet Cells Population [Change from Baseline Goblet cells population at 90 days]

   Increase of 20% from baseline

7. Corneal Epithelization Defects With Fluorescein [Final Visit (day 90)]

   Percentage of the damaged epithelium of the ocular surface, reduction of staining according to the oxford scale.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18 to < 90 years old

• Both sexes

• Mild to moderate tear film dysfunction clinical diagnose

• Mild to moderate clinical stage of the disease

• TBUT > 5 sec. and < 10 sec.

• Schirmer: > 4 mm and < 14 mm

• OSDI < 30 points

• Corneal staining < grade III on the Oxford scale

• Availability to go to each revision when indicated.

Exclusion Criteria:

General Criteria

1. Subjects with topical and/or systemic medication or mechanical devices that interfere determinedly on the results of the study (such as topical immunomodulators, punctal plugs, corticosteroids, preservative artificial tears, contact lenses).

2. Subjects (females) with active sexual life that do not use a contraceptive method.

3. Female subjects who are pregnant or lactating

4. Female subjects with a positive urine pregnancy test

5. Positive drug addictions* (verbal interrogatory)

6. Subjects who have participated on any other research clinical trials on the last 40 days

7. Subjects legal or mentally disabled to give an informed consent for participating on this study

8. Subjects who can't comply with the appointments or with every protocol requirement.

Criteria related with ophthalmic ailments

1. Serious tear film dysfunction syndrome TBUT < 5 s Schirmer: < 4 mm OSDI > 30 pints Corneal staining > grade III on the Oxford scale

2. Non perforated corneal ulcer

3. Perforated corneal ulcer

4. Autoimmune corneal ulcer

5. Ocular surface scarring diseases

6. Ocular surface or annexes metaplastic lesions

7. Fibro vascular proliferation lesions on the conjunctival and/or corneal surface (i.e.: pterygium)

8. Concomitant chronic inflammatory diseases on any ocular structure

9. Acute or infectious inflammatory disease

10. Corneal disease potentially requiring a treatment during the following 3 months

11. Use of topical or systemic drug products classified as forbidden

12. Ocular surgical procedures 3 months before the protocol inclusion

13. Treatments or procedures indicated on the tear film dysfunction treatment, as punctal silicone plugs.

14. Posterior segment diseases requiring a treatment or threatening the visual prognosis

15. Retinal diseases potentially requiring treatment during the following 3 months

16. History of penetrating keratoplasty.

17. Soft or hard contact lenses use during the last month from inclusion day

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fernando Rodriguez Sixtos Higuera	Irapuato	Guanajuato	Mexico	36670

Sponsors and Collaborators

• Laboratorios Sophia S.A de C.V.

Investigators

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

Study Documents (Full-Text)

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

More Information

Publications

None provided.

• Responsible Party: Laboratorios Sophia S.A de C.V.
• ClinicalTrials.gov Identifier: NCT03223909
• Other Study ID Numbers: SOPH087-0415/IV
• First Posted: Jul 21, 2017
• Last Update Posted: Oct 31, 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.: dry eye; Chondroitin sulfate; Ocular lubricants
• Additional relevant MeSH terms: Dry Eye Syndromes; Syndrome; Hyaluronic Acid

Study Results

Participant Flow

Arm/Group Title	PRO-087 PF	Systane Ultra	Systane Ultra PF
Arm/Group Description	Preservative free (PF) PRO-087 ophthalmic solution. Dropper bottle. Multidose 1 drop every 4 hours for 90 days. PRO-087: 0.1% sodium hyaluronate, free-preservative 0.18% chondroitin sulphate	Systane Ultra ophthalmic solution, Dropper bottle, Multidose. 1 drop every 4 hours for 90 days. Systane Ultra: Is a sterile solution containing polyethylene glycol 400, propylene glycol, hydroxypropyl-guar, sorbitol, aminomethylpropanol, boric acid, potassium chloride, sodium chloride and POLYQUAD® (poly-hydronium chloride) 0.001% as preservative.	Systane Ultra, preservative free ophthalmic solution, single-use vials. 1 drop every 4 hours for 90 days. Systane Ultra Preservative Free: Polyethylene Glycol 400 0.4%Lubricant, Propylene Glycol 0.3% Lubricant,
Period Title: Overall Study
STARTED	120	109	97
COMPLETED	72	64	81
NOT COMPLETED	48	45	16

Baseline Characteristics

Arm/Group Title	PRO-087 PF	Systane Ultra	Systane Ultra PF	Total
Arm/Group Description	Preservative free (PF) PRO-087 ophthalmic solution. Dropper bottle. Multidose 1 drop every 4 hours for 90 days. PRO-087: 0.1% sodium hyaluronate, free-preservative 0.18% chondroitin sulphate	Systane Ultra ophthalmic solution, Dropper bottle, Multidose. 1 drop every 4 hours for 90 days. Systane Ultra: Is a sterile solution containing polyethylene glycol 400, propylene glycol, hydroxypropyl-guar, sorbitol, aminomethylpropanol, boric acid, potassium chloride, sodium chloride and POLYQUAD® (poly-hydronium chloride) 0.001% as preservative.	Systane Ultra, preservative free ophthalmic solution, single-use vials. 1 drop every 4 hours for 90 days. Systane Ultra Preservative Free: Polyethylene Glycol 400 0.4%Lubricant, Propylene Glycol 0.3% Lubricant,	Total of all reporting groups
Overall Participants	72	64	81	217
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.5 (15.3)	55.0 (17.6)	51.9 (16.2)	54.2 (16.5)
Sex: Female, Male (Count of Participants)
Female	52 72.2%	46 71.9%	63 77.8%	161 74.2%
Male	20 27.8%	18 28.1%	18 22.2%	56 25.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%	0 0%
More than one race	72 100%	64 100%	81 100%	217 100%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Visual Acuity
Description	Best-corrected visual acuity
Time Frame	Change from Baseline visual acuity at 90 days

Outcome Measure Data

Analysis Population Description

the statistical analysis was carried out by intention to treat (ITT)

Arm/Group Title	PRO-087 PF	Systane Ultra	Systane Ultra PF
Arm/Group Description	Preservative free (PF) PRO-087 ophthalmic solution. Dropper bottle. Multidose 1 drop every 4 hours for 90 days. PRO-087: 0.1% sodium hyaluronate, free-preservative 0.18% chondroitin sulphate	Systane Ultra ophthalmic solution, Dropper bottle, Multidose. 1 drop every 4 hours for 90 days. Systane Ultra: Is a sterile solution containing polyethylene glycol 400, propylene glycol, hydroxypropyl-guar, sorbitol, aminomethylpropanol, boric acid, potassium chloride, sodium chloride and POLYQUAD® (poly-hydronium chloride) 0.001% as preservative.	Systane Ultra, preservative free ophthalmic solution, single-use vials. 1 drop every 4 hours for 90 days. Systane Ultra Preservative Free: Polyethylene Glycol 400 0.4%Lubricant, Propylene Glycol 0.3% Lubricant,
Measure Participants	72	64	81
Base Line	0.187 (0.25)	0.215 (0.26)	0.219 (0.23)
Final Visit	0.172 (0.24)	0.187 (0.24)	0.176 (0.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-087 PF, Systane Ultra, Systane Ultra PF
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	it was considered as not inferior when the treatments did not present differences greater than 20% Statistical analysis of groups in the baseline visit versus final visit
Statistical Test of Hypothesis	p-Value	0.080
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PRO-087 PF, Systane Ultra, Systane Ultra PF
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	it was considered as not inferior when the treatments did not present differences greater than 20% Statistical analysis between groups in the final visit
Statistical Test of Hypothesis	p-Value	0.848
	Comments
	Method	ANOVA
	Comments

2. Secondary Outcome

Title	Corneal Epithelization Defects With Rose of Bengal
Description	Percentage of the damaged epithelium of the ocular surface, reduction of staining according to the oxford scale.
Time Frame	Final Visit (day 90)

Outcome Measure Data

Analysis Population Description

the statistical analysis was carried out by intention to treat

Arm/Group Title	PRO-087 PF	Systane Ultra	Systane Ultra PF
Arm/Group Description	Preservative free (PF) PRO-087 ophthalmic solution. Dropper bottle. Multidose 1 drop every 4 hours for 90 days. PRO-087: 0.1% sodium hyaluronate, free-preservative 0.18% chondroitin sulphate	Systane Ultra ophthalmic solution, Dropper bottle, Multidose. 1 drop every 4 hours for 90 days. Systane Ultra: Is a sterile solution containing polyethylene glycol 400, propylene glycol, hydroxypropyl-guar, sorbitol, aminomethylpropanol, boric acid, potassium chloride, sodium chloride and POLYQUAD® (poly-hydronium chloride) 0.001% as preservative.	Systane Ultra, preservative free ophthalmic solution, single-use vials. 1 drop every 4 hours for 90 days. Systane Ultra Preservative Free: Polyethylene Glycol 400 0.4%Lubricant, Propylene Glycol 0.3% Lubricant,
Measure Participants	72	64	81
Normal (0)	80.6	73.4	77.8
Very mild (1)	18.1	25	19.1
Mild (2)	1.4	1.6	3.1
Moderate (3)	0	0	0
Severe (4)	0	0	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-087 PF, Systane Ultra, Systane Ultra PF
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	it was considered as not inferior when the treatments did not present differences greater than 20%
Statistical Test of Hypothesis	p-Value	0.468
	Comments
	Method	Chi-squared, Corrected
	Comments

3. Secondary Outcome

Title	Tear Film Break-up Time (TBUT)
Description	Tear breakup time (TBUT) is a clinical test used to assess for evaporative dry eye disease. To measure TBUT, fluorescein is instilled into the patient's tear film and the patient is asked not to blink while the tear film is observed under a broad beam of cobalt blue illumination. The TBUT is recorded as the number of seconds that elapse between the last blink and the appearance of the first dry spot in the tear film, as seen in this progression of these slit lamps photos over time. A TBUT under 10 seconds is considered abnormal
Time Frame	Base line and Final Visit (day 90)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PRO-087 PF	Systane Ultra	Systane Ultra PF
Arm/Group Description	Preservative free (PF) PRO-087 ophthalmic solution. Dropper bottle. Multidose 1 drop every 4 hours for 90 days. PRO-087: 0.1% sodium hyaluronate, free-preservative 0.18% chondroitin sulphate	Systane Ultra ophthalmic solution, Dropper bottle, Multidose. 1 drop every 4 hours for 90 days. Systane Ultra: Is a sterile solution containing polyethylene glycol 400, propylene glycol, hydroxypropyl-guar, sorbitol, aminomethylpropanol, boric acid, potassium chloride, sodium chloride and POLYQUAD® (poly-hydronium chloride) 0.001% as preservative.	Systane Ultra, preservative free ophthalmic solution, single-use vials. 1 drop every 4 hours for 90 days. Systane Ultra Preservative Free: Polyethylene Glycol 400 0.4%Lubricant, Propylene Glycol 0.3% Lubricant,
Measure Participants	72	64	81
Base Line	7.08 (1.01)	7.10 (1.01)	7.10 (1.01)
Final visit	8.28 (2.3)	8.46 (2.6)	8.52 (2.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-087 PF, Systane Ultra, Systane Ultra PF
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	population analysis was per protocol
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PRO-087 PF, Systane Ultra
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	population analysis was per protocol
Statistical Test of Hypothesis	p-Value	0.650
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Schirmer Test
Description	Schirmer's test determines whether the eye produces enough tears to keep it moist. This test is used when a person experiences very dry eyes or excessive watering of the eyes. It poses no risk to the subject. A negative (more than 10 mm of moisture on the filter paper in 5 minutes) test result is normal. Both eyes normally secrete the same amount of tears.
Time Frame	Base line and Final Visit (day 90)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PRO-087 PF	Systane Ultra	Systane Ultra PF
Arm/Group Description	Preservative free (PF) PRO-087 ophthalmic solution. Dropper bottle. Multidose 1 drop every 4 hours for 90 days. PRO-087: 0.1% sodium hyaluronate, free-preservative 0.18% chondroitin sulphate	Systane Ultra ophthalmic solution, Dropper bottle, Multidose. 1 drop every 4 hours for 90 days. Systane Ultra: Is a sterile solution containing polyethylene glycol 400, propylene glycol, hydroxypropyl-guar, sorbitol, aminomethylpropanol, boric acid, potassium chloride, sodium chloride and POLYQUAD® (poly-hydronium chloride) 0.001% as preservative.	Systane Ultra, preservative free ophthalmic solution, single-use vials. 1 drop every 4 hours for 90 days. Systane Ultra Preservative Free: Polyethylene Glycol 400 0.4%Lubricant, Propylene Glycol 0.3% Lubricant,
Measure Participants	72	64	81
basal visit (day 1)	9.48 (2.5)	9.05 (2.7)	9.25 (2.7)
Final Visit	10.19 (4.2)	12.21 (4.5)	12.16 (5.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-087 PF, Systane Ultra
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	It was considered as not inferior when the treatments did not present differences greater than 20% Statistical analysis of Humylub® Ofteno (PRO-087) versus Systane® Ultra PF at the final visit.
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	ANOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PRO-087 PF, Systane Ultra PF
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	It was considered as not inferior when the treatments did not present differences greater than 20% Statistical analysis of Humylub® Ofteno (PRO-087) versus Systane® Ultra PF at the final visit.
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	ANOVA
	Comments

5. Secondary Outcome

Title	Adverse Events
Description	Presence of adverse events modifying some of the abovementioned criteria or others, evaluated as serious.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

Statistical analysis was performed by protocol (PP)

Arm/Group Title	PRO-087 PF	Systane Ultra	Systane Ultra PF
Arm/Group Description	Preservative free (PF) PRO-087 ophthalmic solution. Dropper bottle. Multidose 1 drop every 4 hours for 90 days. PRO-087: 0.1% sodium hyaluronate, free-preservative 0.18% chondroitin sulphate	Systane Ultra ophthalmic solution, Dropper bottle, Multidose. 1 drop every 4 hours for 90 days. Systane Ultra: Is a sterile solution containing polyethylene glycol 400, propylene glycol, hydroxypropyl-guar, sorbitol, aminomethylpropanol, boric acid, potassium chloride, sodium chloride and POLYQUAD® (poly-hydronium chloride) 0.001% as preservative.	Systane Ultra, preservative free ophthalmic solution, single-use vials. 1 drop every 4 hours for 90 days. Systane Ultra Preservative Free: Polyethylene Glycol 400 0.4%Lubricant, Propylene Glycol 0.3% Lubricant,
Measure Participants	120	109	97
Number [percentage of adverse events]	19.2	21.1	20.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-087 PF, Systane Ultra, Systane Ultra PF
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	the statistical analysis was carried out by intention to treat It was considered as not inferior when the treatments did not present differences greater than 20%
Statistical Test of Hypothesis	p-Value	0.930
	Comments
	Method	Chi-squared
	Comments

6. Secondary Outcome

Title	Ocular Surface Disease Index (OSDI)
Description	The OSDI, which was created to order to quickly assess the symptoms of ocular irritation in dry eye disease and how they affect functioning related to vision. This 12-item questionnaire assesses dry eye symptoms and the effects it has on vision-related function in the past of the patient's life. The questionnaire has 3 subscales: ocular symptoms, vision-related function, and environmental triggers. Patients rate their responses on a 0 to 4 scale with 0 corresponding to "none of the time" and 4 corresponding to "all of the time." A final score is calculated which ranges from 0 to 100 with scores 0 to 12 representing normal, 13 to 22 representing mild dry eye disease, 23 to 32 representing moderate dry eye disease, and greater than 33 representing severe dry eye disease.
Time Frame	Change from Baseline OSDI at 90 days

Outcome Measure Data

Analysis Population Description

The statistical analysis was carried out by intention to treat

Arm/Group Title	PRO-087 PF	Systane Ultra	Systane Ultra PF
Arm/Group Description	Preservative free (PF) PRO-087 ophthalmic solution. Dropper bottle. Multidose 1 drop every 4 hours for 90 days. PRO-087: 0.1% sodium hyaluronate, free-preservative 0.18% chondroitin sulphate	Systane Ultra ophthalmic solution, Dropper bottle, Multidose. 1 drop every 4 hours for 90 days. Systane Ultra: Is a sterile solution containing polyethylene glycol 400, propylene glycol, hydroxypropyl-guar, sorbitol, aminomethylpropanol, boric acid, potassium chloride, sodium chloride and POLYQUAD® (poly-hydronium chloride) 0.001% as preservative.	Systane Ultra, preservative free ophthalmic solution, single-use vials. 1 drop every 4 hours for 90 days. Systane Ultra Preservative Free: Polyethylene Glycol 400 0.4%Lubricant, Propylene Glycol 0.3% Lubricant,
Measure Participants	72	64	81
Base Line	16.59 (7.3)	15.74 (7.0)	16.31 (7.7)
Final Visit	5.99 (8.2)	7.47 (8.8)	6.32 (7.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-087 PF, Systane Ultra, Systane Ultra PF
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	it was considered as not inferior when the treatments did not present differences greater than 20%
Statistical Test of Hypothesis	p-Value	0.548
	Comments
	Method	ANOVA
	Comments

7. Secondary Outcome

Title	Goblet Cells Population
Description	Increase of 20% from baseline
Time Frame	Change from Baseline Goblet cells population at 90 days

Outcome Measure Data

Analysis Population Description

the statistical analysis was carried out by intention to treat

Arm/Group Title	PRO-087 PF	Systane Ultra	Systane Ultra PF
Arm/Group Description	Preservative free (PF) PRO-087 ophthalmic solution. Dropper bottle. Multidose 1 drop every 4 hours for 90 days. PRO-087: 0.1% sodium hyaluronate, free-preservative 0.18% chondroitin sulphate	Systane Ultra ophthalmic solution, Dropper bottle, Multidose. 1 drop every 4 hours for 90 days. Systane Ultra: Is a sterile solution containing polyethylene glycol 400, propylene glycol, hydroxypropyl-guar, sorbitol, aminomethylpropanol, boric acid, potassium chloride, sodium chloride and POLYQUAD® (poly-hydronium chloride) 0.001% as preservative.	Systane Ultra, preservative free ophthalmic solution, single-use vials. 1 drop every 4 hours for 90 days. Systane Ultra Preservative Free: Polyethylene Glycol 400 0.4%Lubricant, Propylene Glycol 0.3% Lubricant,
Measure Participants	72	64	81
Base Line	341.2 (136.9)	338.5 (150.6)	327.4 (146.8)
Final Visit	447.3 (173.4)	413.5 (157.7)	442.6 (147.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-087 PF, Systane Ultra, Systane Ultra PF
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	it was considered as not inferior when the treatments did not present differences greater than 20%
Statistical Test of Hypothesis	p-Value	0.170
	Comments
	Method	ANOVA
	Comments

8. Secondary Outcome

Title	Corneal Epithelization Defects With Fluorescein
Description	Percentage of the damaged epithelium of the ocular surface, reduction of staining according to the oxford scale.
Time Frame	Final Visit (day 90)

Outcome Measure Data

Analysis Population Description

the statistical analysis was carried out by intention to treat

Arm/Group Title	PRO-087 PF	Systane Ultra	Systane Ultra PF
Arm/Group Description	Preservative free (PF) PRO-087 ophthalmic solution. Dropper bottle. Multidose 1 drop every 4 hours for 90 days. PRO-087: 0.1% sodium hyaluronate, free-preservative 0.18% chondroitin sulphate	Systane Ultra ophthalmic solution, Dropper bottle, Multidose. 1 drop every 4 hours for 90 days. Systane Ultra: Is a sterile solution containing polyethylene glycol 400, propylene glycol, hydroxypropyl-guar, sorbitol, aminomethylpropanol, boric acid, potassium chloride, sodium chloride and POLYQUAD® (poly-hydronium chloride) 0.001% as preservative.	Systane Ultra, preservative free ophthalmic solution, single-use vials. 1 drop every 4 hours for 90 days. Systane Ultra Preservative Free: Polyethylene Glycol 400 0.4%Lubricant, Propylene Glycol 0.3% Lubricant,
Measure Participants	72	64	81
Normal (0)	52.8	53.1	53.7
Very mild (1)	36.8	36.7	10.4
Mild (2)	10.4	9.4	15.4
Moderate (3)	0	0	2.5
Severe (4)	0	0.8	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PRO-087 PF, Systane Ultra, Systane Ultra PF
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	it was considered as not inferior when the treatments did not present differences greater than 20%
Statistical Test of Hypothesis	p-Value	0.085
	Comments
	Method	Chi-squared, Corrected
	Comments

Adverse Events

Time Frame	Adverse events were monitored and recorded throughout the study, an average of 2 years, since october 2016 to october 2018.
Arm/Group Title	PRO-087 PF		Systane Ultra		Systane Ultra PF
Arm/Group Description	Preservative free (PF) PRO-087 ophthalmic solution. Dropper bottle. Multidose 1 drop every 4 hours for 90 days. PRO-087: 0.1% sodium hyaluronate, free-preservative 0.18% chondroitin sulphate		Systane Ultra ophthalmic solution, Dropper bottle, Multidose. 1 drop every 4 hours for 90 days. Systane Ultra: Is a sterile solution containing polyethylene glycol 400, propylene glycol, hydroxypropyl-guar, sorbitol, aminomethylpropanol, boric acid, potassium chloride, sodium chloride and POLYQUAD® (poly-hydronium chloride) 0.001% as preservative.		Systane Ultra, preservative free ophthalmic solution, single-use vials. 1 drop every 4 hours for 90 days. Systane Ultra Preservative Free: Polyethylene Glycol 400 0.4%Lubricant, Propylene Glycol 0.3% Lubricant,
All Cause Mortality
	PRO-087 PF		Systane Ultra		Systane Ultra PF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/120 (0%)		0/109 (0%)		0/28 (0%)
Serious Adverse Events
	PRO-087 PF		Systane Ultra		Systane Ultra PF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/120 (0%)		0/109 (0%)		0/97 (0%)
Other (Not Including Serious) Adverse Events
	PRO-087 PF		Systane Ultra		Systane Ultra PF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/120 (20%)		29/109 (26.6%)		19/97 (19.6%)
Ear and labyrinth disorders
Ringing in ears	0/120 (0%)	0	1/109 (0.9%)	1	0/97 (0%)	0
Eye disorders
bacterial conjunctivitis	3/120 (2.5%)	3	0/109 (0%)	0	0/97 (0%)	0
blepharitis	0/120 (0%)	0	1/109 (0.9%)	1	0/97 (0%)	0
Defect of the corneal epithelium	6/120 (5%)	6	6/109 (5.5%)	6	4/97 (4.1%)	4
Allergic conjunctivitis	1/120 (0.8%)	1	4/109 (3.7%)	4	1/97 (1%)	1
Eyelid spasm	0/120 (0%)	0	1/109 (0.9%)	1	0/97 (0%)	0
Feeling of burning	2/120 (1.7%)	2	1/109 (0.9%)	1	2/97 (2.1%)	2
Blurry vision	0/120 (0%)	0	2/109 (1.8%)	2	0/97 (0%)	0
Red eye	1/120 (0.8%)	1	1/109 (0.9%)	1	3/97 (3.1%)	3
Prurito en el ojo	3/120 (2.5%)	3	3/109 (2.8%)	3	2/97 (2.1%)	2
Tearing	4/120 (3.3%)	4	0/109 (0%)	0	2/97 (2.1%)	2
Foreign body sensation in the eyes	1/120 (0.8%)	1	2/109 (1.8%)	2	1/97 (1%)	1
Eye pain	0/120 (0%)	0	1/109 (0.9%)	1	0/97 (0%)	0
Gastrointestinal disorders
enteroviric gastroenteritis	0/120 (0%)	0	2/109 (1.8%)	2	0/97 (0%)	0
Episodes of aggravated nausea	0/120 (0%)	0	1/109 (0.9%)	1	0/97 (0%)	0
Bacterial gastroenteritis	0/120 (0%)	0	0/109 (0%)	0	1/97 (1%)	1
Food poisoning	0/120 (0%)	0	0/109 (0%)	0	1/97 (1%)	1
General disorders
Anxiety	0/120 (0%)	0	1/109 (0.9%)	1	0/97 (0%)	0
Nuisance in the area of application	1/120 (0.8%)	1	0/109 (0%)	0	0/97 (0%)	0
Light fever	0/120 (0%)	0	0/109 (0%)	0	1/97 (1%)	1
Musculoskeletal and connective tissue disorders
Flexo-extension injury	1/120 (0.8%)	1	0/109 (0%)	0	0/97 (0%)	0
Nervous system disorders
Headache	1/120 (0.8%)	1	1/109 (0.9%)	1	3/97 (3.1%)	3
Renal and urinary disorders
Bacterial urinary infection	0/120 (0%)	0	0/109 (0%)	0	1/97 (1%)	1
Urethritis	2/120 (1.7%)	2	0/109 (0%)	0	0/97 (0%)	0
Respiratory, thoracic and mediastinal disorders
Faringoamigdalitis	0/120 (0%)	0	2/109 (1.8%)	2	1/97 (1%)	1
cough	1/120 (0.8%)	1	0/109 (0%)	0	0/97 (0%)	0
flu	2/120 (1.7%)	2	0/109 (0%)	0	1/97 (1%)	1
Skin and subcutaneous tissue disorders
Contact dermatitis	1/120 (0.8%)	1	0/109 (0%)	0	1/97 (1%)	1
Cellulitis of the finger	1/120 (0.8%)	1	0/109 (0%)	0	0/97 (0%)	0
Allergy	0/120 (0%)	0	1/109 (0.9%)	1	0/97 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

IPs may not share, disclose or partially or completely publish the information of this research in order to request and receive written approval from the sponsor.