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

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:

• Preservative free PRO-087 ophthalmic solution. Dropper bottle. Multidose 1 drop every 4 hours for 90 days.
• Systane® Ultra ophthalmic solution. Dropper bottle. Multidose. 1 drop every 4 hours for 90 days.
• Systane ® Ultra preservative free ophthalmic solution. Single-use vials. 1 drop every 4 hours for 90 days.

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

• 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).
• Subjects (females) with active sexual life that do not use a contraceptive method.
• Female subjects who are pregnant or lactating
• Female subjects with a positive urine pregnancy test
• Positive drug addictions* (verbal interrogatory)
• Subjects who have participated on any other research clinical trials on the last 40 days
• Subjects legal or mentally disabled to give an informed consent for participating on this study
• Subjects who can't comply with the appointments or with every protocol requirement.

Criteria related with ophthalmic ailments

• Serious tear film dysfunction syndrome TBUT < 5 s Schirmer: < 4 mm OSDI > 30 pints Corneal staining > grade III on the Oxford scale
• Non perforated corneal ulcer
• Perforated corneal ulcer
• Autoimmune corneal ulcer
• Ocular surface scarring diseases
• Ocular surface or annexes metaplastic lesions
• Fibro vascular proliferation lesions on the conjunctival and/or corneal surface (i.e.: pterygium)
• Concomitant chronic inflammatory diseases on any ocular structure
• Acute or infectious inflammatory disease
• Corneal disease potentially requiring a treatment during the following 3 months
• Use of topical or systemic drug products classified as forbidden
• Ocular surgical procedures 3 months before the protocol inclusion
• Treatments or procedures indicated on the tear film dysfunction treatment, as punctal silicone plugs.
• Posterior segment diseases requiring a treatment or threatening the visual prognosis
• Retinal diseases potentially requiring treatment during the following 3 months
• History of penetrating keratoplasty.
• Soft or hard contact lenses use during the last month from inclusion day