Comparison of Efficacy and Ocular Surface Assessment Between BRIDIN-plus and Combigan in Glaucoma or Ocular Hypertensive

Study Overview
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Brief Summary
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Comparison of Efficacy and Ocular Surface Disease Assessment between BRIDIN-plus Eye drops and Combigan Eye drops in Glaucoma or Ocular Hypertensive Patients : Phase 4, Parallel Group Design, Investigator-blind, Active-control, Randomized, Multi-center Trial

Detailed Description
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The purpose of this clinical trial is to prove lower negative effects on ocular surface disease and higher patient compliance of a single-use formula BRIDIN-PLUS® eye drops group, comparing to a multi-use formula COMBIGAN® eye drops after 12 weeks of administration to glaucoma or ocular hypertensive patients.

Official Title
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Comparison of Efficacy and Ocular Surface Disease Assessment Between BRIDIN- PLUS® Eye Drops and COMBIGAN® Eye Drops in Glaucoma or Ocular Hypertensive Patients

Conditions
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Glaucoma, Ocular Hypertensive

Intervention / Treatment
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* Drug: BRIDIN-plus Eye drops
* Drug: Combigan Eye drops


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Male or female adults who are 19 years or older with a diagnosis of glaucoma or intraocular hypertension A person who has completed an appropriate washout period if glaucoma treatment medication has been used Intraocular pressure measured by Goldman applanation tonometer at visit 2 is 15mmHg or above and less than 40mmHg A person who has signed the written consent form by himself/herself or by a legal representative Exclusion Criteria: A patient with primary close angle glaucoma, congenital glaucoma, secondary glaucoma caused by steroids Best corrected visual acuity of both eyes measured by Snellen acuity charts is 20/80 (decimal 0.25) or less A patient with progressive intraocular inflammation Central corneal thickness is less than 470um or greater than 591ums A patient who has had lacrimal punctual occlusion done within the last 3 monthds or who has eye surgery plan during the clinical study Pregnant or lactating women Other cases if investigators judge the patient is difficult to participate the clinical trial

Ages Eligible for Study
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Minimum Age: 19 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BRIDIN-plus Eye drops<br>One drop in the eyes, twice a day, approximately 12 hours apart. | Drug: BRIDIN-plus Eye drops<br>* One drop in the eyes, twice a day, approximately 12 hours apart.<br>* Other names: Brimonidine tartrate 2.0mg, Timolol maleate 6.8mg(without preservative);|
| Active Comparator: Combigan Eye drops<br>One drop in the eyes, twice a day, approximately 12 hours apart. | Drug: Combigan Eye drops<br>* One drop in the eyes, twice a day, approximately 12 hours apart.<br>* Other names: Brimonidine tartrate 2.0mg, Timolol maleate 6.8mg(with preservative);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corneal staining test | Corneal staining score is evaluated according to the oxford grading system after blue fluorescein staining under a slit lamp biomicroscope of cobalt blue light source using a yellow filter. Corneal surface is divided into 3 areas and evaluated from grade 0 indicating that there is no staining to grade 5 indicating denser staining due to severe corneal defect. (The score ranges from 0 to 5, with higher scores indicate worse symtoms.) | 12 weeks after administration | 
| Conjunctival staining test | Conjunctival staining score is evaluated after blue fluorescein staining under a slit lamp biomicroscope, by NEI(The National Eye Institute) scale. Conjunctival surface is divided into 6 areas and evaluated from grade 0 indicating that there is no staining to grade 3 indicating denser staining due to severe conjunctival defect. | 12 weeks after administration | 
| Ocular surface disease index (OSDI) | Ocular surface disease index include 12 items comprising of assessment of vision related functioning (5 items), ocular symptoms(4 items) and environmental factors that may cause symptoms (3 items). Each item is 5-point Likert scale in which a higher score indicates more severe symptoms. A total score is classified as normal (0-12), mild (13-22), moderate (23-32) and severe (33 or more) and it is evaluated based on grades and score changes | 12 weeks after administration | 
| Questionnaire (Evaluation of Satisfaction with Medication, Ocular tolerance) | treatment administration satisfaction and ocular tolerance are evaluated through questionnaires. Treatment administration satisfaction questionnaire includes the convenience of use and storage of investigational products and ocular tolerance evaluation questionnaire includes symptom severity(0 3) and symptom duration(briefly, persistent) for 8 symptoms of stinging/burning, sticky eyes, itching, blurred vision, foreign-body sensation, dryness, photophobia, pain. Medication compliance is evaluated with MGL-MAQ-Korean version. | 12 weeks after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corneal staining test | Corneal staining score is evaluated according to the oxford grading system after blue fluorescein staining under a slit lamp biomicroscope of cobalt blue light source using a yellow filter. Corneal surface is divided into 3 areas and evaluated from grade 0 indicating that there is no staining to grade 5 indicating denser staining due to severe corneal defect. (The score ranges from 0 to 5, with higher scores indicate worse symtoms.) | 4 weeks after administration | 
| Conjunctival staining test | Conjunctival staining score is evaluated after blue fluorescein staining under a slit lamp biomicroscope, by NEI(The National Eye Institute) scale. Conjunctival surface is divided into 6 areas and evaluated from grade 0 indicating that there is no staining to grade 3 indicating denser staining due to severe conjunctival defect. | 4 weeks after administration | 
| Ocular surface disease index (OSDI) | Ocular surface disease index include 12 items comprising of assessment of vision related functioning (5 items), ocular symptoms(4 items) and environmental factors that may cause symptoms (3 items). Each item is 5-point Likert scale in which a higher score indicates more severe symptoms. A total score is classified as normal (0-12), mild (13-22), moderate (23-32) and severe (33 or more) and it is evaluated based on grades and score changes | 4 weeks after administration | 
| IOP(Intraocular pressure) | The same tonometer (Goldman applanation tonometer) should be used. In the case of bilateral glaucoma, intraocular pressure of the right eye is first measured and a higher one is used. If intraocular pressures of both eyes are the same, intraocular pressures of the right eye is used. In unilateral glaucoma, intraocular pressures of an eye with glaucoma is used. | 4, 12 weeks after administration | 
| Tear break up time (TBUT) | Corneal staining score is evaluated after blue fluorescein staining on a 6-point scale according to oxford grading system under a slit lamp biomicroscope with a yellow filter offering cobalt blue light. After blue fluorescein staining, a participant is asked to blink their eyes. Then, time from the last blinking to the point when black spots, lines or loss of fluorescein are observed is measured in seconds under a slit lamp biomicroscope with a yellow filter offering cobalt blue light. The mean value of three repeated measurement results are used | 4, 12 weeks after administration | 
| Hyperemia score | Prior to fluorescein staining, hyperemia evaluation is done to the bulbar conjunctiva and the limbus, the border between cornea and conjunctiva using Efron Grading Scales. grade 0: normal; grade 1: trace; grade 2: mild; grade 3: moderate; grade 4: severe (The scales from grade 0 to 4, with higer scales indicate greater severity of symptoms.) | 4, 12 weeks after administration |