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

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

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.

Study Overview

• Status: Completed
• Conditions: Cataract
• Intervention / Treatment: Drug: Difluprednate Ophthalmic Emulsion 0.05%; Drug: Prednisolone Acetate 1% Phenylephrine hydrochloride 0,12% ophthalmic solution

• Study Type: Interventional
• Enrollment (Actual): 255
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma De Buenos Aires
    • Ciudad Autonoma de Buenos Aire, Ciudad Autonoma De Buenos Aires, Argentina, C1407BDR
      • Laboratorios Poen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Difluprednate Ophthalmic Emulsion 0.05%	Drug: Difluprednate Ophthalmic Emulsion 0.05%; 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.; Other Names: Tolf®
Active Comparator: Comparator; Prednisolone Acetate 1% - Phenylephrine 0.12% Ophthalmic Suspension	Drug: Prednisolone Acetate 1% Phenylephrine hydrochloride 0,12% ophthalmic solution; 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.

What is the study measuring?

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).

Collaborators and Investigators

• Sponsor: Laboratorios Poen
• Investigators: Study Director: Jorge Tosi, M.D., Laboratorios Poen

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2019
• Primary Completion (Actual): May 24, 2020
• Study Completion (Actual): July 21, 2020

Study Registration Dates

• First Submitted: November 5, 2020
• First Submitted That Met QC Criteria: November 10, 2020
• First Posted (Actual): November 17, 2020

Study Record Updates

• Last Update Posted (Actual): May 12, 2023
• Last Update Submitted That Met QC Criteria: May 11, 2023
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Lens Diseases; Inflammation; Cataract; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Respiratory System Agents; Pharmaceutical Solutions; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Ophthalmic Solutions; Phenylephrine; Oxymetazoline; Difluprednate
• Other Study ID Numbers: DIFLUPRED03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes