Pterygium, Ocular Pain, Ocular Inflammation, Post-surgical Inflammation
Conditions
Keywords
zebesten, ocular anti-inflammatory, ocular analgesic, pterygium, anti-inflammatory non-steroidal ophthalmic
Brief summary
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.
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
Interventions
DRUGPRO-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
OTHERPlacebo
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
Sponsors
Laboratorios Sophia S.A de C.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The double-blind study is a procedure in which the subject and the principal investigator do not know which of the intervention groups was assigned to the subject of the study. To achieve the blinding of the drug, both the investigational drug and the placebo, will be packed in the same bottle, containing the same legends on the label. The blinding codes are protected by a person outside the study designated by the sponsor. The codes are also available in the research center (fully sealed), so that they can be consulted by the Investigator in the event that the subject presents a serious adverse event, prior authorization of the study sponsor, as well as strict continuous blindness during the analysis of data.
Intervention model description
A controlled, randomized, double-blind, masked clinical trial comparing the safety and efficacy of PRO-155 in the treatment of conjunctival hyperemia in pterygium I to III compared to placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Breakup Time (BUT) | will be evaluated at the end of the treatment at the final visit (day 21) | 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. |
| Conjunctival Hyperemia (CH) | will be evaluated at the end of the treatment at the final visit (day 21) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Epithelial Defects (ED) Green Lissamine | will be evaluated at the end of the treatment at the final visit (day 21) | 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. |
| Intraocular Pressure (IOP) | will be evaluated at the end of the treatment at the final visit (day 21) | 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 |
| Presence of Adverse Events (EAS) | will be evaluated at the end of the treatment at the final visit (day 36) | 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 |
| Number of Eyes With Chemosis | will be evaluated at the end of the treatment at the final visit (day 21) | 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. |
| Epithelial Defects (ED) Fluorescein Stain | will be evaluated at the end of the treatment at the final visit (day 21) | 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. |
| Visual Capacity | will be evaluated at the end of the treatment at the final visit (day 21) | 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. |
| Number of Eyes With Foreign Body Sensation (FBS) | will be evaluated at the end of the treatment at the final visit (day 21) | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Eyes With Ocular Burning (OB) | will be evaluated at the end of the treatment at the final visit (day 21) | 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. |
Countries
Mexico
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PRO-155 Pro-155: 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac for 20 days
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 | 41 |
| PRO-155 Pro-155: 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac for 20 days
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 | 82 |
| Placebo Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac
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 | 42 |
| Placebo Placebo 1 drop 2 times a day in the period of vigil in the conjunctival cul-de-sac
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 | 84 |
| Total | 249 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 7 | 17 |
Baseline characteristics
| Characteristic | Placebo | Total | PRO-155 |
|---|---|---|---|
| Age, Continuous | 57.17 years STANDARD_DEVIATION 14.4 | 55.51 years STANDARD_DEVIATION 13.45 | 53.8 years STANDARD_DEVIATION 13.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 42 Participants | 83 Participants | 41 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 30 Participants | 60 Participants | 30 Participants |
| Sex: Female, Male Male | 12 Participants | 23 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 76 | 0 / 90 |
| other Total, other adverse events | 13 / 76 | 19 / 90 |
| serious Total, serious adverse events | 0 / 76 | 0 / 90 |
Outcome results
Primary
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.
Time frame: will be evaluated at the end of the treatment at the final visit (day 21)
Population: Statistical analysis was performed by protocol (PP)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO-155 | Breakup Time (BUT) | 8.29 seconds | Standard Deviation 2.2 |
| Placebo | Breakup Time (BUT) | 7.63 seconds | Standard Deviation 2.3 |
p-value: 0.045Wilcoxon (Mann-Whitney)
Primary
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.
Time frame: will be evaluated at the end of the treatment at the final visit (day 21)
Population: statistical analysis by protocol (PP)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PRO-155 | Conjunctival Hyperemia (CH) | Very mild | 39 eyes |
| PRO-155 | Conjunctival Hyperemia (CH) | Moderate | 5 eyes |
| PRO-155 | Conjunctival Hyperemia (CH) | Mild | 25 eyes |
| PRO-155 | Conjunctival Hyperemia (CH) | Severe | 0 eyes |
| PRO-155 | Conjunctival Hyperemia (CH) | Normal | 0 eyes |
| Placebo | Conjunctival Hyperemia (CH) | Severe | 0 eyes |
| Placebo | Conjunctival Hyperemia (CH) | Normal | 0 eyes |
| Placebo | Conjunctival Hyperemia (CH) | Very mild | 29 eyes |
| Placebo | Conjunctival Hyperemia (CH) | Mild | 36 eyes |
| Placebo | Conjunctival Hyperemia (CH) | Moderate | 8 eyes |
p-value: 0.133Chi-squared, Corrected
Secondary
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.
Time frame: will be evaluated at the end of the treatment at the final visit (day 21)
Population: the statistical analysis was carried out by protocol (PP)
| Arm | Measure | Category | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| PRO-155 | Epithelial Defects (ED) Fluorescein Stain | Fluorescein Grade 4 | 0 eyes |
| PRO-155 | Epithelial Defects (ED) Fluorescein Stain | Fluorescein Grade 5 | 0 eyes |
| PRO-155 | Epithelial Defects (ED) Fluorescein Stain | Fluorescein Grade 0 | 31 eyes |
| PRO-155 | Epithelial Defects (ED) Fluorescein Stain | Fluorescein Grade 1 | 27 eyes |
| PRO-155 | Epithelial Defects (ED) Fluorescein Stain | Fluorescein Grade 2 | 11 eyes |
| PRO-155 | Epithelial Defects (ED) Fluorescein Stain | Fluorescein Grade 3 | 0 eyes |
| Placebo | Epithelial Defects (ED) Fluorescein Stain | Fluorescein Grade 2 | 9 eyes |
| Placebo | Epithelial Defects (ED) Fluorescein Stain | Fluorescein Grade 4 | 0 eyes |
| Placebo | Epithelial Defects (ED) Fluorescein Stain | Fluorescein Grade 1 | 33 eyes |
| Placebo | Epithelial Defects (ED) Fluorescein Stain | Fluorescein Grade 5 | 0 eyes |
| Placebo | Epithelial Defects (ED) Fluorescein Stain | Fluorescein Grade 3 | 0 eyes |
| Placebo | Epithelial Defects (ED) Fluorescein Stain | Fluorescein Grade 0 | 31 eyes |
p-value: 0.117Chi-squared, Corrected
Secondary
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.
Time frame: will be evaluated at the end of the treatment at the final visit (day 21)
| Arm | Measure | Group | Value (COUNT_OF_UNITS) |
|---|---|---|---|
| PRO-155 | Epithelial Defects (ED) Green Lissamine | Green lissamine grade 0 | 41 eyes |
| PRO-155 | Epithelial Defects (ED) Green Lissamine | Green lissamine grade 1 | 21 eyes |
| PRO-155 | Epithelial Defects (ED) Green Lissamine | Green lissamine grade 2 | 4 eyes |
| PRO-155 | Epithelial Defects (ED) Green Lissamine | Green lissamine grade 3 | 3 eyes |
| PRO-155 | Epithelial Defects (ED) Green Lissamine | Green lissamine grade 4 | 0 eyes |
| PRO-155 | Epithelial Defects (ED) Green Lissamine | Green lissamine grade 5 | 0 eyes |
| Placebo | Epithelial Defects (ED) Green Lissamine | Green lissamine grade 4 | 0 eyes |
| Placebo | Epithelial Defects (ED) Green Lissamine | Green lissamine grade 0 | 44 eyes |
| Placebo | Epithelial Defects (ED) Green Lissamine | Green lissamine grade 3 | 0 eyes |
| Placebo | Epithelial Defects (ED) Green Lissamine | Green lissamine grade 1 | 21 eyes |
| Placebo | Epithelial Defects (ED) Green Lissamine | Green lissamine grade 5 | 0 eyes |
| Placebo | Epithelial Defects (ED) Green Lissamine | Green lissamine grade 2 | 8 eyes |
p-value: 0.333Chi-squared, Corrected
Secondary
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
Time frame: will be evaluated at the end of the treatment at the final visit (day 21)
Population: the statistical analysis was carried out by protocol (PP)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO-155 | Intraocular Pressure (IOP) | 12.45 mmHg | Standard Deviation 2.1 |
| Placebo | Intraocular Pressure (IOP) | 13.08 mmHg | Standard Deviation 1.8 |
p-value: 0.058Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: will be evaluated at the end of the treatment at the final visit (day 21)
Population: the statistical analysis was carried out by protocol (PP)
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| PRO-155 | Number of Eyes With Chemosis | 0 eyes |
| Placebo | Number of Eyes With Chemosis | 0 eyes |
Secondary
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.
Time frame: will be evaluated at the end of the treatment at the final visit (day 21)
Population: the statistical analysis was carried out by protocol (PP)
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| PRO-155 | Number of Eyes With Foreign Body Sensation (FBS) | 10 eyes |
| Placebo | Number of Eyes With Foreign Body Sensation (FBS) | 18 eyes |
p-value: 0.114Fisher Exact
Secondary
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
Time frame: will be evaluated at the end of the treatment at the final visit (day 36)
Population: The analysis of adverse events was done by intention to treat (ITT)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PRO-155 | Presence of Adverse Events (EAS) | 13 Participants |
| Placebo | Presence of Adverse Events (EAS) | 19 Participants |
p-value: 0.394Fisher Exact
Secondary
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.
Time frame: will be evaluated at the end of the treatment at the final visit (day 21)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PRO-155 | Visual Capacity | 0.043 LogMAR | Standard Deviation 0.1 |
| Placebo | Visual Capacity | 0.059 LogMAR | Standard Deviation 0.2 |
p-value: 0.056t-test, 2 sided
Other Pre-specified
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.
Time frame: will be evaluated at the end of the treatment at the final visit (day 21)
Population: the statistical analysis was carried out by protocol (PP)
| Arm | Measure | Value (COUNT_OF_UNITS) |
|---|---|---|
| PRO-155 | Number of Eyes With Ocular Burning (OB) | 8 eyes |
| Placebo | Number of Eyes With Ocular Burning (OB) | 11 eyes |
p-value: 0.626Fisher Exact