Clinical Study of the Efficacy of the Ophthalmic Emulsion PRO-145 for Inflammation and Pain After Phacoemulsification

Study Overview
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Brief Summary
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objective: To evaluate the efficacy of the ophthalmic emulsion PRO-145 in the treatment of inflammation and pain after phacoemulsification. Hypothesis: The use of the ophthalmic emulsion PRO-145 is effective in decreasing the inflammatory response evaluated by means of cellularity in the anterior chamber, after phacoemulsification. Methodology: Phase III clinical trial, double-blind, controlled, parallel group, multicentre, randomized. Number of patients: 178 subjects divided into 2 groups (89 subjects per group), who will provide an eye for the evaluation of efficacy. Diagnosis and main inclusion criteria: Diagnosis: Postoperative phacoemulsification and foldable intraocular lens placement in a bag.

Detailed Description
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The study subjects will be recruited from various research centers in western and central Mexico. Each research center has a monitoring plan specified according to the recruitment capabilities of the same, which must be at least once a month, where the queries of your data entered into the electronic case report report will be reported to the center. (e-CRF) for which it has as time limit the next monitoring visit to make the pertinent changes. The report of adverse events will be made according to the standard operating procedure (PNO) where it specifies, according to Official Mexican Standard 220 (NOM 220), that the signs or symptoms of adverse events will be reported based on the Medical Dictionary. for Regulatory Activities, for which the sponsor has version 20.1 in Spanish. For serious adverse events (SAEs) will be reported in accordance with the standardized operation procedure of pharmacovigilance of the sponsor, which adheres to the guidelines of NOM 220 and international regulations, these will be reported in the regulatory framework to the regulatory entity within a period of time no more than 7 days. The study is registered in the National Registry of Clinical Trials (RNEC), entity equivalent to Clinical Trials in Mexico. The quality assurance plan is carried out by the sponsor through the Quality Assurance agent in Clinical Research, whose function is to conduct inspections and audits of the research sites to document and generate reports of deviations from the protocol. In addition to the visits of the monitoring plan, the reliability of the data is guaranteed. To verify the integrity, veracity and reliability of the data entered into the e-CRF, the monitors of each center will check the information uploaded to the portal with that reported in the source document of the principal investigator (PI), such as clinical notes, clinical history and documents. and formats attached to the research protocol, physical case report format, as well as those provided by the sponsor to the PI (subject's diary and quality and satisfaction survey). The e-CRF used for this clinical study is provided by an internationally certified provider with the highest quality standards, protection of information under current regulations and confidentiality guarantee. The information that the PIs enter into the e-CRF is collated and verified by the clinical monitors and by the service provider's personnel, later reviewed and approved by the medical ophthalmologist researcher and by the Clinical Security Pharmacologist, who authorize the monitored data of clinical information and safety of the study molecule, respectively.

Official Title
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Clinical Study of the Efficacy of the Ophthalmic Emulsion PRO-145 for the Management of Inflammation and Pain After Phacoemulsification Compared to Prednisolone Acetate 1%.

Conditions
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Cataract

Intervention / Treatment
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* Drug: Difluprednate 0.05%
* Drug: Prednefrin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent. Age ≥ 18 years. Both sexes. Postoperative cataract surgery by phacoemulsification. o That they have met the criteria for phacoemulsification and a classification of the lens opacity classification system (LOCS) III cataract of Opalescence of the nucleus (NO) ≥2 and Kernel color (NC) ≥2. Exclusion Criteria: Pregnant women, lactating or planning to get pregnant. Women of reproductive age and who do not have a hormonal contraceptive method, intrauterine device or bilateral tubal obstruction. Participation in another clinical research study ≤ 30 days before the baseline visit. Have previously participated in this same study with the contralateral eye. That they can not comply with their attendance at appointments or with all the requirements of the protocol. Medical and therapeutic criteria. Surgery in both eyes in the same surgical shift. Time> 24 hours after having surgery. Intraocular lens placement outside the bag. Presentation of rupture of the posterior capsule, with or without the presence of vitreous. Carrying out an iridectomy, or lesion of the pupillary sphincter during phacoemulsification surgery. Scheduled for surgical intervention in the contralateral eye during the study period. History of glaucoma or ocular hypertension. History of increased Intraocular pressure (IOP) with the use of steroids. Intraocular pressure (IOP) ≥24. History of uveitis. Presence of corneal abrasion or corneal ulceration in the study eye. Use of steroids or topical non steroidal anti inflammatory drugs, 24 hours prior to surgery and until the start of instillation of investigational drugs. Use of anticoagulants, systemic steroids or immunomodulators in the last two weeks Periocular injection of any steroid in the study eye 4 weeks before the start of the instillation of the investigational drugs. Use of storage steroids 2 months prior to the start of instillation of investigational drugs. Presence or suspicion of keratitis and / or viral, bacterial or fungal conjunctivitis. Presence or suspicion of endophthalmitis. Presence or suspicion of toxic syndrome of the anterior segment. Severe corneal edema that does not allow assessment of the anterior chamber Macular diseases. Diabetes Mellitus with glycosylated hemoglobin (A1C) ≥ 6.5% (48 mmol / mol) or fasting glucose (no caloric intake by ≥ 8 hours) of ≥ 126 mg / dL (7.0 mmol / L). Any disease or condition that requires the use of topical or systemic nonsteroidal anti-inflammatories (NSAIDs) during the time of intervention. Any disease or condition that requires the use of steroids other than topical ophthalmic application. Subjects with a single eye. Any condition or disease that at the discretion of the principal investigator (IP) does not make the subject suitable for the study. Known hypersensitivity to the components of the products under investigation.

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: double-blind, controlled, parallel group, multicentre, randomized
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRO-145.<br>Difluprednate 0.05%. Prepared by Sophia Laboratories, S.A. of C.V., Zapopan, Jalisco, Mexico. | Drug: Difluprednate 0.05%<br>* Dosage: 1 drop 4 times a day (every 4 hours) during the period of vigil in the operated eye, for 14 days. Dose reduction for 14 days at the discretion of the principal investigator.<br>* Other names: PRO-145;|
| Active Comparator: Prednefrin<br>Prednefrin® SF. Prednisolone Acetate 1%. Prepared by Allergan, S.A. of C.V. | Drug: Prednefrin<br>* 1 drop 4 times a day (every 4 hours) during the period of vigil in the operated eye, for 14 days. Dose reduction for 14 days at the discretion of the principal investigator. - Route of administration: topical ophthalmic<br>* Other names: Difluprednate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Ability (VA) | The VA will be evaluated basally, 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 3 meters from the subject to be evaluated. The result of the Snellen fraction will be transformed to its decimal equivalent in LogMAR, ex. 20/20= 1.0, 20/25=0.8, 20/40= 0.5, 20/200= 1.0, etc. The subjects will be averaged by group. | day 28 at the final visit | 
| Adverse Events | The evaluation of adverse events requires a questioning conducted by the principal investigator and the appropriate exploratory techniques for its detection. the number of cases with adverse events will be reported per study arm | day 28 at the final visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cellularity in the Anterior Chamber | unit: degrees, Direct observation (Biomicroscopy). Scale for anterior chamber cellularity. Grade/Number of cells Grade / Number of cells 0 Any ½ + 1-5 + 6-15 + 16-25 + 26-60 + More than 60 the cellularity will be measured according to the scale that is added next, considering as normal the degree 0, and abnormal any other degree. | day 28 at the final visit | 
| Clinical Corneal Edema | The evaluation of clinical edema will be evaluated by the Efron scale, which is a series of factorial sections of the cornea, including features such as grooves and folds. The Efron scale has a strong correlation with variations in intensity. The number will be reported according to the rating awarded. Efron Scale: 0 Normal, 1 very slight, 2 mild, 3 moderate and 4 severe. | day 28 at the final visit | 
| Flare | In the presence of intraocular inflammation, the increased permeability of the non-pigmented layer of the ciliary epithelium, the posterior epithelium of the iris and the vascular endothelium of the iris results in the accumulation of cells and proteins (visible to the examiner as flare) in the anterior chamber. Using a light beam of 0.2mm X 0.2mm directed obliquely to the anterior chamber with a forward inclination of the light source (slit lamp tower) the degree of flare and cellularity will be determined according to the group of work of standardization for the nomenclature of uveitis. Flare scale 0 There is no flare + Mild + Moderate (iris and crystalline clearly visible) + Marking (iris and crystalline slightly blurred) + More than 60 (fibrin) | day 28 at the final visit | 
| Central Thickness of the Retina | By means of optical coherence tomography (OCT) the Retinal central thickness (GCR) will be measured. OCT is a noninvasive imaging test that uses light waves to take photographs of the cross section of the retina (the light-sensitive tissue that lines the back of the eye).With a OCT, each of the characteristic layers of the retina can be observed, allowing mapping and measuring its thickness a micrometer result will be obtained and the analysis will be carried out between groups. | day 28 at the final visit | 
| Conjunctival Hyperemia | Conjunctival hyperemia is defined as the simplest reaction of the conjunctiva to a stimulus, a red appearance secondary to the vasodilation of the conjunctival vessels of variable intensity, we will use the Efron scale for conjunctival hyperemia. 0 normal very slight mild moderate severe | day 28 at the final visit | 
| Intraocular Pressure | Tonometry is the objective measure of Intraocular pressure, based primarily on the force required to flatten the cornea, or the degree of corneal indentation produced by a fixed force. Goldman's tonometry is based on the Imbert-Fick principle. the result will be expressed in millimeters of mercury and the comparison between groups will be carried out | day 28 at the final visit | 
| Symptomatology Post Instillation | The subject will be questioned if after applying the medication he felt burning, pruritus, a foreign body sensation and blurred vision. Presence or absence: it will be marked as present (1) or absent (0) for each of the symptoms questioned | day 28 at the final visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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corticosteroid, anti-inflammatory steroid, phacoemulsification