Phase IV Clinical Study to Compare the Efficacy of the Ophthalmic Solution Humylub Ofteno® PF With Hyabak® and Lagricel Ofteno® PF as Treatment for Dry Eye.

Study Overview
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Brief Summary
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Phase IV, non inferiority, controlled, open, multicenter clinical study to compare the efficacy of the Ophthalmic Solution Humylub Ofteno® PF against Hyabak® and Lagricel Ofteno® PF applied quater in die (QID) for 30 days in patients with mild to moderate dry eye disease.

Official Title
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Non Inferiority Phase IV Clinical Study, to Compare the Efficacy of the Ophthalmic Solution Humylub Ofteno® PF Against Hyabak® and Lagricel Ofteno® PF When Applied on the Ocular Surface of Patients With Mild to Moderate Dry Eye.

Conditions
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Dry Eye

Intervention / Treatment
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* Drug: Sodium hyaluronate 0.1%/chondroitin sulfate 0.18%
* Drug: Sodium hyaluronate 0.15%
* Drug: Sodium hyaluronate 0.4%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Being capable of voluntarily grant a signed informed consent. Being willing and able to meet the requirements of the study such as attending programmed visits, treatment plan and other study procedures. Age ≥ 18 years old Women in child-bearing age must assure the continuation (start ≥ 30 days prior to informed consent signing) of a hormonal contraceptive method or intrauterine device (IUD) during the study. Presenting a mild to moderate dry eye disease diagnosis, defined as: OSDI score ≥ 13, plus one of the following: More than 5 dots of corneal staining More than 9 dots of conjunctival staining Tear break-up time < 10 seconds Exclusion Criteria: - Pregnancy, breastfeeding or planning to become pregnant during the time of the study Having participated in clinical trials within 30 days prior to the eligibility visit. Having participated previously in this study. BCVA equal or worse than 20/200, in either eye. Diagnosis of any of the following: Allergic, viral or bacterial conjunctivitis Anterior blepharitis Parasite infestation of any ocular or annex structures (Demodex, for example) Unresolved history of ocular trauma Scarring diseases of the ocular surface Corneal or conjunctival ulcers Filamentary keratitis Neurotrophic keratitis Bullous keratopathy Neoplastic diseases of the ocular surface or ocular annexes Diseases presenting fibrovascular proliferations on the corneal or conjunctival surface. Any retinal or posterior segment diseases that require treatment or threat the visual outcome. Glaucoma Any palpebral alteration that causes eyelid malposition, limiting the adequate closure or aperture of this structures, or that cause tearing. Requiring management for dry eye that includes implementation of treatments described in the step 2 management recommendations of the Tear Film & Ocular Surface Society's Dry Eye Work Shop II (TFO DEWS II). Previous history of drug addiction within the last 2 years prior to signing this study's informed consent form. Having a previous history of any ophthalmological surgical procedure, within the last 3 months prior to the informed consent signing date. Being a contact lens user, rigid or soft. Inclusion is possible if the use of contact lenses is suspended both during the study period and at least 15 days prior inclusion takes place. Previous history of any medical affliction, acute or chronic, that according to the investigator may increase either the risk to the patient for participating in this study or the risk of interference of the accurate interpretation of results. Known hypersensitivity to any of the components of the products used in this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase IV, non inferiority, controlled, open, comparative, multicenter clinical study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1; Humylub Ofteno® PF<br>Humylub Ofteno® PF (sodium hyaluronate 0.1%/chondroitin sulfate 0.18%) ophthalmic solution applied QID for 30 days. | Drug: Sodium hyaluronate 0.1%/chondroitin sulfate 0.18%<br>* Application of one drop of Humylub Ofteno® PF (Sodium hyaluronate 0.1%/chondroitin sulfate 0.18%) QID in both eyes (OU) during 30 days.<br>* Other names: PRO-087;|
| Active Comparator: Arm 2; Hyabak®<br>Hyabak® PF (sodium hyaluronate 0.15%) ophthalmic solution applied QID for 30 days. | Drug: Sodium hyaluronate 0.15%<br>* Application of one drop of Hyabak® PF (Sodium hyaluronate 0.15%) QID in OU during 30 days.<br>* Other names: Hyabak® PF;|
| Active Comparator: Arm 3; Lagricel Ofteno® PF<br>Lagricel Ofteno® PF (sodium hyaluronate 0.4%) ophthalmic solution applied QID for 30 days. | Drug: Sodium hyaluronate 0.4%<br>* Application of one drop of Lagricel Ofteno® PF (Sodium Hyaluronate 0.4%) QID in OU during 30 days.<br>* Other names: PRO-037;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Ocular Surface Disease Index (OSDI) | It is a 12-item questionnaire used to evaluate symptoms associated with dry eye disease, as well as classify their severity. According the obtained score, categories are as follows: normal (0-12 points), mild (13-22 points), moderate (23-32 points), or severe (33-100 points). | Days: 0 (± 2) (eligibility visit), 17 - 19 (± 1) (first follow-up visit), and 31 - 33 (± 1) (final visit). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Noninvasive keratograph break-up time (NIKBUT) | This evaluation will be performed through an Oculus Keratograph 5M, and the parameter first break-up time will be recorded as NIKBUT. This study can take place within a time frame of 0 - 2 days between eligibility and baseline visits, and ± 2 of fist follow-up and final visits. | Days: 0 - 2 (baseline visit),17 - 19 (± 1) (first follow-up visit), and 31 - 33 (± 1) (final visit). | 
| Change in conjunctival and corneal staining with lissamine green | The evaluation will take place after applying the lissamine green stain on the ocular surface and evaluating the resulting staining pattern. This will be measured through the Oxford scale which includes 6 grades: Absent (0), Minimal (I), Mild (II), Moderate (III), Marked (IV), Severe (V). | Days: 0 (eligibility visit), 17 - 19 (± 1) (first follow-up visit), and 31 - 33 (± 1) (final visit). | 
| Change in conjunctival and corneal staining with fluorescein | The evaluation will take place after applying the fluorescein stain on the ocular surface and evaluating the resulting staining pattern. This will be measured through the Oxford scale which includes 6 grades: Absent (0), Minimal (I), Mild (II), Moderate (III), Marked (IV), Severe (V). | Days: 0 (eligibility visit), 17 - 19 (± 1) (first follow-up visit), and 31 - 33 (± 1) (final visit). | 
| Change in conjunctival hyperemia | Rate of conjunctival hyperemia will be evaluated through the Efron scale which includes 5 grades: Normal (0), Very Mild (I), Mild (II), Moderate (3), and Severe (4). | Days: 0 (eligibility visit), 17 - 19 (± 1) (first follow-up visit), and 31 - 33 (± 1) (final visit). | 
| Incidence of related non expected adverse events | Presence/absence of related non expected adverse events. | Days: 0 (eligibility visit), 0 - 2 (baseline visit),17 - 19 (± 1) (first follow-up visit), 31 - 33 (± 1) (final visit), and 38 - 40 (± 1) (safety call). | 
| Change in Best Corrected Visual Acuity (BCVA) | With the patient's best possible refractive correction, visual acuity will be evaluated through the Snellen chart. Its notation (fraction or decimal) is described as the distance from the chart at which the test is performed, divided by the distance at which a letter equals vertically 5 minutes of arc. | Days: 0 (eligibility visit), 17 - 19 (± 1) (first follow-up visit), and 31 - 33 (± 1) (final visit). | 
| Change in incidence of chemosis | Chemosis will be evaluated as present (if conjunctiva separates from the sclera in ≥ 1/3 of the palpebral opening area or if it exceeds the eyelid's gray line) or absent. | Days: 0 (eligibility visit), 17 - 19 (± 1) (first follow-up visit), and 31 - 33 (± 1) (final visit). |