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

Laboratorios Sophia S.A de C.V.326 enrolled

Overview

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.

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Visual Acuity

Best-corrected visual acuity

Time frame: Change from Baseline visual acuity at 90 days

Secondary Outcomes

Corneal Epithelization Defects With Rose of Bengal

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

Time frame: Final Visit (day 90)

Tear Film Break-up Time (TBUT)

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)

Schirmer Test

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)

Adverse Events

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

Time frame: 90 days

Ocular Surface Disease Index (OSDI)

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

Goblet Cells Population

Increase of 20% from baseline

Time frame: Change from Baseline Goblet cells population at 90 days

Corneal Epithelization Defects With Fluorescein