Difluprednate vs. a Prednisolone Acetate - Phenylephrine on Post-operative Inflammation Following Cataract Surgery.

Study Overview
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Brief Summary
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This controlled, randomized, double blind, multicenter study will be carried out to demonstrate that the topical ophthalmic nanoemulsion of difluprednate 0.05% (Tolf®, Poen Laboratories), has a high anti-inflammatory efficacy, which would allow it to be administered after cataract surgery 1 drop, twice a day , starting the day before surgery and continuing for 14 days and 1 drop, once a day for the following 2 weeks, achieving an adequate anti-inflammatory activity, with the benefit of reducing the toxicity on the ocular surface, improving the dosage and adherence to treatment. The follow-up time will be 28 days and the outcome measures will be evaluated in a baseline (time 0), on day 1, on day 4 and on day 28 after surgery. The active control will be prednisolone acetate 1% + phenylephrine hydrochloride 0.12% topical ophthalmic suspension (Prednefrin® Forte, Allergan Argentina) given 1 drop, 4 times a days and 1 drop, twice a day for the next 2 weeks. Corneal thickness, central macula thickness, endothelial cell count, intraocular pressure, visual acuity, anterior chamber clearance and lacrimal film recovery will be evaluated.

Official Title
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Efficacy and Safety of Difluprednate Ophthalmic Emulsion vs. a Fixed-Combination of Prednisolone Acetate - Phenylephrine Ophthalmic Suspension on Post-operative Inflammation Following Cataract Surgery.

Conditions
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Cataract

Intervention / Treatment
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* Drug: Difluprednate Ophthalmic Emulsion 0.05%
* Drug: Prednisolone Acetate 1% Phenylephrine hydrochloride 0,12% ophthalmic solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of both sexes between 45 and 65 years old (women who are not fertile) who undergo cataract surgery N2 and N3, defined according to BCN10, Decimal classification of cataracts. That the surgical technique is ultrasonic phacoemulsification. Patients who have an initial corneal thickness between 500 and 570 µm inclusive. Patients with initial intraocular pressure between 12 and 18 mm Hg inclusive. Patients with an endothelial cell count greater than 1000 cells / mm2 Exclusion Criteria: Patients who use eye medication, except eye lubricant. Patients who before surgery have not been able to dilate their pupil more than 5 mm Patients who have been treated with corticosteroids or systemic anti-inflammatory drugs for 2 weeks prior to enrollment Patients who have received periocular corticosteroid injections in the study eye within the previous 4 weeks or used depot corticosteroids within 2 months prior to enrollment Patients who have received a topical ocular corticosteroid or non-steroidal anti-inflammatory drug (NSAID) within 24 hours prior to enrollment History of glaucoma or ocular hypertension in the study eye, history or presence of endogenous uveitis, or corneal abrasion or ulceration Patients with a diagnosis or suspicion of keratoconjunctival disease caused by viruses, bacteria, or fungi Patients which presents an allergy to the drug to be tested or to any similar drug such as other corticosteroids History of increased intraocular pressure due to the use of corticosteroids Patients with pathological macular features Diabetics Breastfeeding women Patients with rheumatoid arthritis. Patients treated with Amiodarone

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Difluprednate Ophthalmic Emulsion 0.05% | Drug: Difluprednate Ophthalmic Emulsion 0.05%<br>* 1 drop, 2 times a day, starting the day before surgery and continuing for 14 post-surgical days and 1 drop, once a day for the next 2 weeks.<br>* Other names: Tolf®;|
| Active Comparator: Comparator<br>Prednisolone Acetate 1% - Phenylephrine 0.12% Ophthalmic Suspension | Drug: Prednisolone Acetate 1% Phenylephrine hydrochloride 0,12% ophthalmic solution<br>* 1 drop, 4 times a day, starting the day before surgery and continuing for 14 post-surgical days and 1 drop, twice a day for the next 2 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline corneal thickness between treatments | Demonstrate that 0.05% difluprednate ophthalmic nanoemulsion administered 1 drop, 2 times a day, beginning the day before cataract surgery and continuing for the first 14 postoperative days and then 1 drop, once a day for the next 14 days, it does not present an anti-inflammatory efficacy lower than treatment with prednisolone acetate 1% + phenylephrine hydrochloride 0.12% ophthalmic suspension administered 1 drop, 4 times a day starting the day before surgery and continuing during the first 14 post-surgical days and 1 drop , 2 times a day for the next 14 days, for the treatment of postsurgical inflammation, in patients operated on for N2 and N3 cataracts. Difluprednate 0.05% ophthalmic nanoemulsion will not be clinically inferior than Prednisolone acetate 1% + 0.12% phenylephrine hydrochloride ophthalmic suspension, if the difference in corneal thickness obtained with OCT between the baseline day and the post-surgical day it does not differ beyond 17 µm between treatments. | Baseline to visit 3 (96 hours from surgery) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retinal Thickness | Retinal Thickness measured by Optical Coherence Tomography (mm) | Day before surgery (-1); Day 1 after surgery (1); Day 4 after surgery (4); 28 days post surgery (28) | 
| Corneal endothelial cell count | Corneal endothelial cell count measured by specular microscope (cells/mm2) | Day before surgery (-1); Day after surgery (1); Day 4 after surgery (4); 28 days post surgery (28). | 
| Visual acuity | Visual acuity measured by visual acuity standardized chart (20/20) | Day before surgery (-1); Day after surgery (1); Day 4 after surgery (4); 28 days post surgery (28). | 
| Flare and cell on anterior chamber | Presence of flare and cells on anterior chamber using slit lamp (biomicroscopy) | Day before surgery (-1); Day after surgery (1); Day 4 after surgery (4); 28 days post surgery (28). | 
| Intraocular pressure | Intraocular pressure measured by Goldmann tonometer (mmHg) | Day before surgery (-1); Day after surgery (1); Day 4 after surgery (4); 28 days post surgery (28). | 
| Equal safety profile of both treatments | Report of adverse events of both treatments under study | Day before surgery (-1); Day 1 after surgery (1); Day 4 after surgery (4); 28 days post surgery (28) | 
| Corneal Thickness by pachymetry | Corneal Thickness (mm) | Day before surgery (-1); Day after surgery (1); Day 4 after surgery (4); 28 days post surgery (28). |