Clinical Trial to Compare the Safety and Efficacy of Nanodrop®

Study Overview
=================
Brief Summary
-----------------
Study design: Phase I-II clinical trial, comparative, non-inferiority with active control, parallel groups, double blind with randomisation. Safety analysis when completing the visits of the first 12 subjects of the Nanodrop® group, if there are less than 20% of unexpected Events (EA), related to the research product, recruitment is continued until the sample is completed for efficacy analysis objectives Security: Evaluate the safety of the ophthalmic application of Nanodrop® by quantifying the incidence of unexpected Adverse Events (EA) related to the research product (PI). Effectiveness: Demonstrate the non-inferiority of Nanodrop® compared to Systane® Balance, in the efficacy of the treatment of patients with dry eye, by means of the Ocular Surface Disease Index (OSDI). Hypothesis Security: H0 = Nanodrop® is safe in its ophthalmic application as it presents an incidence of unexpected adverse events related to the research drug, less than 20% of the population of Nanodrop® safety group. H1 = Nanodrop® is not safe in its ophthalmic application, as it presents an incidence of unexpected adverse events related to the research drug, exceeding 20% of the population of Nanodrop® safety group. Effectiveness: H0 = Nanodrop® is lower than Systane® Balance by more than 5 points in the OSDI test score. H1 = Nanodrop® is lower than Systane® Balance by 5 points or less in the OSDI test score. Number of subjects: n = 126 evaluable subjects 63 evaluable subjects per group (both eyes). Main inclusion criteria: Dry eye diagnosis Duration of intervention treatment: 28 days Approximate duration of the subject in the study: 35 days

Official Title
-----------------
Phase I-II Clinical Trial to Compare the Safety and Efficacy of Nanodrop® Against Systane® Balance in the Treatment of Dry Eye Patients

Conditions
-----------------
Dry Eye

Intervention / Treatment
-----------------
* Drug: Nanodrop®
* Drug: Systane Balance


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have the ability to voluntarily grant your signed informed consent Power and willingness to comply with scheduled visits treatment plan and other study procedures Be willing to modify the activities of your lifestyle. Be of legal age Women of reproductive age should ensure continuation (initiated ≥ 30 days prior to the signing of the Informed Consent Form or ICF) of using a hormonal contraceptive method or intrauterine device (IUD) during the study period Present a dry eye diagnosis, defined by: OSDI ≥ 13 points plus one of the following: Corneal staining with more than 5 sites Conjunctival staining with more than 9 sites Breakup Time of lacrimal film (BUT) <10 seconds: Exclusion Criteria: In the case of women: being pregnant, breastfeeding or planning to get pregnant within the study period. Have participated in another clinical research study ≤ 30 days before the scrutiny visit. Having previously participated in this study. Present a Better Corrected Visual Acuity (MAVC) of 20/200 or worse in one of the eyes. Present an added ophthalmological diagnosis of: Allergic, viral or bacterial conjunctivitis. Anterior blepharitis. Demodex. Eye parasitic infections. Unresolved eye trauma. Healing diseases of the ocular surface. Corneal or conjunctival ulcers. Filamentous keratitis. Neurotrophic keratitis. Bullous keratopathy. Neoplastic diseases on the ocular surface or annexes. Diseases with fibrovascular proliferations on the conjunctival and / or corneal surface. Diseases in the retina and / or posterior segment that require treatment or threaten the visual prognosis. Glaucoma Have a management of your dry eye that requires the implementation of stage 2 treatments of the recommendations in the treatment and management by stages for the dry eye disease from the Dry Eye Workshop II of The Tear Film and Ocular Surface Society (DEWS II, TFOS). Have a history of drug addiction or current drug dependence or within the last two years prior to the signing of the Informed Consent Form. Have a history of ocular surgical procedure within the last 3 months prior to the signing of the Informed Consent Form. Be a user of soft or hard contact lenses. You can enter if you can suspend your use during the study, you must turn 15 days without using the contact lens before inclusion. Having another medical condition, acute or chronic, that at the discretion of the researcher could increase the risk associated with participation in the study or administration of the product under investigation, or that could interfere with the interpretation of the results of the study. Present known hypersensitivity to the components of the products under investigation. Be or have an immediate family member (for example: spouse, parent / legal guardian, brother or child) who is an employee of the research site or the sponsor, and who participates directly in this study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase I-II clinical trial, comparative, non-inferiority with active control, double blind with randomisation. Safety analysis when completing the visits of the first 12 subjects
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nanodrop® (PRO-176)<br>- Nanodrop®. 0.6% propylene glycol. Ophthalmic emulsion Laboratorios Sophia, S.A. from C.V. Route of administration: Ophthalmic. | Drug: Nanodrop®<br>* minimum to meet 1 drop 4 times a day, both eyes<br>* Other names: Propylene glycol 0.6%;|
| Active Comparator: Systane® Balance<br>Systane® Balance. 0.6% propylene glycol. Ophthalmic emulsion Alcon Laboratories, Inc. Route of administration: Ophthalmic. | Drug: Systane Balance<br>* minimum to meet 1 drop 4 times a day, both eyes<br>* Other names: Propylene glycol 0.6%;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ocular Surface Disease Index (OSDI) | OSDI is a questionnaire designed to measure eye surface irritation with Rasch analysis to produce estimates on a linear interval scale (ratings: 0-100). Similar to the index for ocular surface diseases, the ocular comfort index (OCI) evaluates symptoms. It contains items that focus on the discomfort associated with alterations of the ocular surface. Each of these questions has two parts, which concern separately the frequency and severity of symptoms. | will be evaluated at the end of the treatment (day 29, final visit) | 
| Incidence of unexpected events related to the research product | the adverse events will be evaluated with a scale of Present / Absent, it is a nominal variable, the normal value is absent | during the 29 days of evaluation, including the safety call | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| visual acuity (VA) | Visual acuity (VA) is a test of visual function. It will be evaluated at baseline, without refractive correction with the Snellen chart.Which will be located in a place with adequate lighting, natural or artificial and at a distance of 3meters from the subject to be evaluated. The snellen chart consists of a booklet with 11 lines composed of letters, each line has a different size and a different weighting. the subject is placed at a safe distance and the contralateral eye to which it will be evaluated is covered, then the examiner detects until the line can clearly see the letters given he or she a score, the normal score for a VA is 20/20. | will be evaluated at the end of the treatment (day 29, final visit) | 
| Epithelial Defects (ED) Fluorescein stain | The epithelial defects will be evaluated by fluorescein, it is a discrete variable that will be realized by direct observation, It will be qualified according to the Eye Staining Rating (CTO) of the International Alliance of Clinical Collaboration of Sjögren (SICCA).According to the CTO, grade 0 corresponds to the absence of dotted epithelial erosions (EEP); Grade 1 is defined as the presence of 1-5 EEP; Grade 2 corresponds to 6-30 EEP; and> 30 EEP will be classified as grade 3. Additionally a qualification point will be added if: 1) EEP is presented in the central portion of the cornea with a diameter of 4mm; 2) filaments are observed and 3) confluent staining patches are observed, including linear stains | will be evaluated at the end of the treatment (day 29, final visit) | 
| epithelial Defects (ED) Green lissamine | The epithelial defects will be evaluated by green lissamine, it is a discrete variable that will be realized by direct observation, It will be qualified according to the Eye Staining Rating (CTO) of the International Alliance of Clinical Collaboration of Sjögren (SICCA). In the CTO, grade 0 is defined as the presence of 0 to 9 lissamine green staining points in the interpalpebral bulbar conjunctiva (qualifying the temporal and nasal portion separately); grade 1 is defined by the presence of 10 to 32 points; grade 2 by 33 to 100; and grade 3 for> 100 points. Due to the difficulty of counting individual points in a moving eye, any area ≥ 4mm2 of confluent points is considered> 100 points | will be evaluated at the end of the treatment (day 29, final visit) | 
| Incidence of expected adverse events | the adverse events will be evaluated with a scale of Present / Absent, it is a nominal variable, the normal value is absent | will be evaluated at the end of the treatment (day 29, final visit) | 
| Tear breakup time (TBUT) | brake up time of the tear film One of the first aspects of the tear film that changes when there is an alteration to the ocular surface is its stability. In general, if the corneal or conjunctival surface is damaged, it is unlikely that a stable tear film can be maintained. The most common method to evaluate tear film stability is the evaluation of TBUT with fluorescein. Once the fluorescein is instilled, with the cobalt blue filter the patient is asked not to blink after having blinked 1 to 2 times. The colored precorneal fluorescein layer will change to less fluorescent or non-fluorescent regions. The time that elapses from the last blink to the appearance of these regions is the TBUT. It will be reported in seconds. | will be evaluated at the end of the treatment (day 29, final visit) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Dry eye, propylene glycol