Phase II Clinical Study to Evaluate the Efficacy of Multidose Lagricel® Ofteno Ophthalmic Solution as Treatment for Dry Eye Disease.

Study Overview
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Brief Summary
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Phase II, comparative, controlled, multicenter, parallel group, open, randomized clinical study. The main outcome variable will be the Ocular Surface Disease Index (OSDI) questionnaire. Three dosage schemes of topical ophthalmic application of Multidose Lagricel® Ofteno (Sodium Hyaluronate 0.4%; preservative free) are to be evaluated in patients diagnosed with mild to severe dry eye. Each group will be exposed to one of the following administration schemes: 1 drop bis in die (BID), 1 drop quater in die (QID), or 1 drop six times per day; instillation will take place in both eyes (OU).

Official Title
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Phase II Clinical Study to Evaluate the Efficacy of Multidose Lagricel® Ofteno Ophthalmic Solution Applied in Three Different Dosage Schemes as Treatment for Mild to Moderate Dry Eye

Conditions
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Dry Eye

Intervention / Treatment
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* Drug: Sodium Hyaluronate Ophthalmic 0.4% BID
* Drug: Sodium Hyaluronate Ophthalmic 0.4% QID
* Drug: Sodium Hyaluronate Ophthalmic 0.4% Six times per day


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years old. 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. 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 between 13 and 32, plus one of the following: More than 5 dots of corneal staining More than 9 dots of conjunctival staining BUT < 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 signing this study's informed consent form. 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 ocular 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 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: Comparative, controlled, multicenter, open, randomized clinical study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Application of one drop of Multidose Lagricel® Ofteno (Sodium Hyaluronate 0.4%) BID in OU during 30 days. | Drug: Sodium Hyaluronate Ophthalmic 0.4% BID<br>* Topical ophthalmic administration of one drop of Multidose Lagricel® Ofteno BID.<br>* Other names: Lagricel® Ofteno;|
| Experimental: Group 2<br>Application of one drop of Multidose Lagricel® Ofteno (Sodium Hyaluronate 0.4%) QID in OU during 30 days. | Drug: Sodium Hyaluronate Ophthalmic 0.4% QID<br>* Topical ophthalmic administration of one drop of Multidose Lagricel® Ofteno QID.<br>* Other names: Lagricel® Ofteno;|
| Experimental: Group 3<br>Application of one drop of Multidose Lagricel® Ofteno (Sodium Hyaluronate 0.4%) 6 times per day in OU during 30 days. | Drug: Sodium Hyaluronate Ophthalmic 0.4% Six times per day<br>* Topical ophthalmic administration of one drop of Multidose Lagricel® Ofteno six times per day.<br>* Other names: Lagricel® Ofteno;|

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 (baseline visit) and 31 (+1) (final visit), | 
| Incidence of adverse events | Presence/absence adverse events, defined as the appearance of any unfavorable reaction in a patient participating in a clinical investigation in which any pharmaceutical product is being administered, regardless of the causal attribution. | Day 33 (+ 1) (safety call). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in tear break-up time (BUT) | After application of fluorescein stain, using a slit lamp and its cobalt blue filter, the time elapsed after instructing the patient to blink 1 or 2 times and the appearance of dry spots on the ocular surface will be counted and reported as BUT. Normally, this parameter is ≥ 10 seconds. | Days: 0 (baseline visit),15 (± 1) (first follow-up visit), and 31 (+ 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 (baseline visit),15 (± 1) (first follow-up visit), and 31 (+ 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 (baseline visit),15 (± 1) (first follow-up visit), and 31 (+ 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 (baseline visit),15 (± 1) (first follow-up visit), and 31 (+ 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 (baseline visit),15 (± 1) (first follow-up visit), and 31 (+ 1) (final visit). | 
| 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 (baseline visit),15 (± 1) (first follow-up visit), and 31 (+ 1) (final visit). | 
| Change in intraocular Pressure (IOP) | Measured through Goldman tonometer in milligrams of mercury (mmHg). After instillation of topical anesthetic (tetracaine 0.5%) and fluorescein stain, IOP will be evaluated. Normal values are considered between 10 and 21 mmHg. | Days: 0 (baseline visit),15 (± 1) (first follow-up visit), and 31 (+ 1) (final visit). |