Efficacy and Safety of PRO-155 on Inflammation of the Conjunctival Surface in Subjects With Grade I-III Pterygium vs Placebo. (PRO-155/IV)

Efficacy and Safety of PRO-155 (Zebesten Ofteno®) on Inflammation of the Conjunctival Surface in Subjects With Grade I-III Pterygium vs Placebo.

Title of the study Efficacy and safety of PRO-155 (Zebesten ofteno®) on inflammation of the conjunctival surface in subjects with grade I-III pterygium vs placebo.

Hypothesis H0. The Zebesten® ophthalmic solution (bromfenac 0.09%) is less effective and safe than placebo in reducing conjunctival hyperemia in subjects with grade I-III pterygium.

H1 The Zebesten® ophthalmic solution (bromfenac 0.09%) is more effective and safe than placebo in reducing conjunctival hyperemia in subjects with grade I-III pterygium.

Objective

To evaluate the efficacy and safety of PRO-155 (bromfenac 009%) ophthalmic solution in the treatment of conjunctival hyperemia and ocular surface inflammation in a clinical model of pterygium grade I to III.

Study Overview

• Status: Completed
• Conditions: Ocular Inflammation; Ocular Pain; Pterygium; Post-surgical Inflammation
• Intervention / Treatment: Drug: PRO-155; Other: Placebo

Detailed Description

Variables to be evaluated Visual ability Intraocular pressure. Ocular surface Exploration of the previous segment. Exploration of the posterior segment. Lacrimal rupture time. Corneal de-epithelialization Conjunctival de-epithelialization Adverse events.

PHARMACOLOGICAL INTERVENTION

The pharmacological intervention will consist of the instillation of the ophthalmological solution in the conjunctival cul-de-sac, during the waking period, to any of the following study groups:

• Group 1:

  • Sodium hyaluronate 0.4% [Lagricel ofteno®] 1 drop 3 times a day in the period of vigil in the conjunctival sac fund (the following application scheme is suggested: start: 7:00 ± 1 hours, continuation: 15:00 ± 1 hour and term: at 19:00 ± 1 hours) for 20 days
  • Pro-155 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac (the following application scheme is recommended: start: 7:15 ± 1 hours and term: at 19:15 ± 1 hours) during 20 days

• Group 2:

  • Sodium hyaluronate 0.4% [Lagricel ofteno®] 1 drop 3 times a day in the period of vigil in the conjunctival sac fund (the following application scheme is suggested: start: 7:00 ± 1 hours, continuation: 15:00 ± 1 hour and term: at 19:00 ± 1 hours) for 20 days
  • Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac (the following application scheme is recommended: start: 7:15 ± 1 hours and term: at 19:15 ± 1 hours) for 20 days

• Study Type: Interventional
• Enrollment (Actual): 166
• Phase: Phase 4

Contacts and Locations

Study Locations

• Mexico
  • Ciudad de México, Mexico, 06700
    • Consultorio PRivado Miguel Angel Villanueva
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44160
      • catarata y glaucoma de occidente S.A de C.V.
    • Guadalajara, Jalisco, Mexico, 44620
      • Novam y Vita

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age of 18 to 90 years.
• Both genders.
• Clinical diagnosis of grade I to III pterygium (temporal, nasal, or bitemporal).
• Possibility of going to the revisions when indicated.

Exclusion Criteria:

• Subjects with topical or systemic medication that interfere decisively in the results of the study; such as topical immunomodulators, NSAIDs, antihistamines, corticosteroids, artificial tears with conservative, vasoconstrictors etc.
• Subjects (female) with active sexual life who do not use a contraceptive method.
• Subjects of the female sex in a pregnant state or who are breastfeeding.
• Subjects of the female sex with pregnancy test in positive urine.
• Positive substance abuse
• Subjects who have participated in any clinical research study in the last 40 days.
• Subjects legally or mentally incapacitated to give their informed consent for their participation in this study.
• Subjects that can not comply with the appointments or with all the requirements of the Protocol.

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: PRO-155; Pro-155: 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac for 20 days	Drug: PRO-155; PRO-155 (Zebesten ofteno®) Active agent: bromfenac 0.90 mg / mL, dropper bottle of low density polyethylene for multidose administration in the form of an ophthalmic solution of 5 mL (milliliters). Sanitary registry in Mexico: 108M2014 Sodium hyaluronate 0.4% [Lagricel ofteno®] 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac; Other Names: zebesten; bromfenac
Placebo Comparator: Placebo; Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac	Other: Placebo; The placebo is constituted by agents, additives and vehicles, of the formulation PRO-155 without pharmacological activity. It is dispensed in dropper bottle of low density polyethylene for multi-dose administration in the form of ophthalmic solution of 5 mL Sodium hyaluronate 0.4% (Lagricel ofteno®) 1 drop 3 times a day in the period of vigil in the conjunctival cul-de-sac

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conjunctival Hyperemia (CH)	Conjunctival hyperemia will be evaluated as an ordinal variable, by direct observation and staged using the Efron scale as Normal / Very Light / Mild / Moderate / Severe. Based on this scale, the normal and mild stages are considered without pathologies or normal. Mild, moderate and severe are considered pathological.	will be evaluated at the end of the treatment at the final visit (day 21)
Breakup Time (BUT)	breakup time lacrimal film is a continuous variable that will be measured in seconds, evaluating the time it takes to break it, is done by direct counting and the normality range and mayor to 10 seconds.	will be evaluated at the end of the treatment at the final visit (day 21)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Epithelial Defects (ED) Green Lissamine	The epithelial defects will be evaluated by means of two stains, green lysine and fluorescein, it is a discrete variable that will be realized by direct observation, it will be staged according to the degrees of the oxford scale that go from 0 to 5 (0-V) according to its severity, where 0 is the normal lower limit and 5 the upper limit of defects.	will be evaluated at the end of the treatment at the final visit (day 21)
Intraocular Pressure (IOP)	the intraocular pressure will be evaluated by means of the Goldman applanation tonometry whose unit of measurement is millimeters of mercury (mmHg), it is a continuous variable and its normality range is between 11 - 21 mmHg	will be evaluated at the end of the treatment at the final visit (day 21)
Presence of Adverse Events (EAS)	primary security variable the adverse events will be evaluated with a scale of Present / Absent, it is a nominal variable, the normal value is absent. Adverse events that are reported until the safety call to the 36th day of the study will be considered for this variable	will be evaluated at the end of the treatment at the final visit (day 36)
Visual Capacity	The visual capacity variable will be reported using as a unit of measure a fraction, this is taken from a visual test with the Snellen primer, it is a Nominal type variable. where the optimal vision is 20/20.	will be evaluated at the end of the treatment at the final visit (day 21)
Number of Eyes With Chemosis	In a normal eye there is no presence of chemosis (it is a sign of irritation of the eye, in which the outer covering of the eye can look like a large blister) its presence indicates a pathological state and it will be evaluated if the subjects present it. The chemosis will be evaluated, as a nominal variable, by direct observation and it will be staged as present and absent, where the normality is that said variable is absent.	will be evaluated at the end of the treatment at the final visit (day 21)
Number of Eyes With Foreign Body Sensation (FBS)	Foreign body sensation will be evaluated, as a nominal variable, by direct observation and it will be staged as present and absent, where the normality is that said variable is absent.	will be evaluated at the end of the treatment at the final visit (day 21)
Epithelial Defects (ED) Fluorescein Stain	The epithelial defects will be evaluated by means of two stains, green lysine and fluorescein, it is a discrete variable that will be realized by direct observation, it will be staged according to the degrees of the oxford scale that go from 0 to 5 (0-V) according to its severity, where 0 is the normal lower limit and 5 the upper limit of defects.	will be evaluated at the end of the treatment at the final visit (day 21)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Eyes With Ocular Burning (OB)	primary tolerability variable Ocular burning is a nominal variable that will be evaluated by direct questioning to the research subject, then it will be staged according to the following scale: Severity: Absent, very mild, mild, moderate and severe, where the normality of severity is absent.Frequency: At all times, almost at all times, 50% of the time, almost in no time, at any time. where the normality of the frequency is in no time.	will be evaluated at the end of the treatment at the final visit (day 21)

Collaborators and Investigators

• Sponsor: Laboratorios Sophia S.A de C.V.

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2017
• Primary Completion (Actual): September 14, 2018
• Study Completion (Actual): October 31, 2018

Study Registration Dates

• First Submitted: April 30, 2018
• First Submitted That Met QC Criteria: April 30, 2018
• First Posted (Actual): May 11, 2018

Study Record Updates

• Last Update Posted (Actual): November 20, 2019
• Last Update Submitted That Met QC Criteria: October 30, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: zebesten; ocular anti-inflammatory; ocular analgesic; pterygium; anti-inflammatory non-steroidal ophthalmic
• Additional Relevant MeSH Terms: Pathologic Processes; Eye Diseases; Conjunctival Diseases; Inflammation; Pterygium; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Bromfenac
• Other Study ID Numbers: SOPH155-0415/IV

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