Safety and Efficacy of Brinzolamide/Brimonidine Fixed Combination

Study Overview
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Brief Summary
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The purpose of this study was to compare the safety and intraocular pressure (IOP)-lowering efficacy of a new fixed combination of brinzolamide/brimonidine (Brinz/Brim) to: its individual components (Brinz and Brim), and the concomitant administration of Brinz and Brim (Brinz+Brim).

Detailed Description
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This study consisted of 5 visits conducted during 2 sequential phases: the screening/eligibility phase, which included a screening visit and 2 eligibility visits, and the treatment phase, which included 2 on-therapy visits conducted at Week 2 and Week 6 (or early exit). A washout period based on previous ocular medication preceded Eligibility Visit 1. Subjects who met all inclusion/exclusion criteria at both eligibility visits were randomized to 1 of 4 study drug groups for 6 weeks. Study drug instillation began the morning after the second eligibility visit. The study was terminated by the sponsor out of caution due to microgel formation in the Brinz/Brim formulation. 13 remaining active subjects were discontinued. Further analysis revealed that neither the drop size nor the concentration of the active ingredients was affected.

Official Title
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Safety and IOP-Lowering Efficacy of Brinzolamide/Brimonidine Fixed Combination Ophthalmic Suspension in Patients With Open-Angle Glaucoma and/or Ocular Hypertension

Conditions
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Open-Angle Glaucoma, Ocular Hypertension

Intervention / Treatment
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* Drug: Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension
* Drug: Brinzolamide ophthalmic suspension, 1%
* Drug: Brimonidine tartrate ophthalmic solution, 0.2%
* Other: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign Informed Consent document. Diagnosis of open-angle glaucoma or ocular hypertension, with mean intraocular pressure within protocol-specified range at eligibility visit/s. Other protocol-specified inclusion criteria may apply. Exclusion Criteria: Females of childbearing potential if pregnant, lactating, or not using highly effective birth control measures. Any form of glaucoma other than open-angle glaucoma. Severe central vision loss in either eye. Chronic, recurrent, or severe inflammatory eye disease. Ocular trauma within the preceding 6 months. Ocular infection or ocular inflammation within the preceding 3 months. Clinically significant or progressive retinal disease such as retinal degeneration, diabetic retinopathy, or retinal detachment. Best-corrected visual acuity score worse than 55 letters using the Early Treatment Diabetic Retinopathy Study chart. Other ocular pathology (including severe dry eye) that may, in the opinion of the Investigator, preclude the administration of study product. Ocular surgery within the preceding 6 months. Ocular laser surgery within the preceding 3 months. Any abnormality preventing reliable applanation tonometry. Any other conditions, including severe illness, which could make the patient, in the opinion of the Investigator, unsuitable for the study. Other protocol-specified exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brinz/Brim<br>Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks. A time lapse of at least 10 minutes was required between instillations of each study drug. | Drug: Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension<br> <br> Other: Vehicle<br>* Inactive ingredients used as placebo<br>|
| Active Comparator: Brinz<br>Brinzolamide ophthalmic suspension, 1% and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks. A time lapse of at least 10 minutes was required between instillations of each study drug. | Drug: Brinzolamide ophthalmic suspension, 1%<br> <br> Other: Vehicle<br>* Inactive ingredients used as placebo<br>|
| Active Comparator: Brim<br>Brimonidine tartrate ophthalmic solution, 0.2% and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks. A time lapse of at least 10 minutes was required between instillations of each study drug. | Drug: Brimonidine tartrate ophthalmic solution, 0.2%<br> <br> Other: Vehicle<br>* Inactive ingredients used as placebo<br>|
| Active Comparator: Brinz+Brim<br>Brinzolamide ophthalmic suspension, 1% and brimonidine tartrate ophthalmic solution, 0.2%: 1 drop each instilled in both eyes 3 times a day for 6 weeks. A time lapse of at least 10 minutes was required between instillations of each study drug. | Drug: Brinzolamide ophthalmic suspension, 1%<br> <br> Drug: Brimonidine tartrate ophthalmic solution, 0.2%<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Intraocular Pressure (IOP) From Baseline to Each of the Assessment Time Points (8 AM, + 2 Hrs, + 7 Hrs, and + 9 Hrs) at Week 6 - Brinz/Brim, Brinz, Brim | The study drug was instilled at 8 AM and +7 hours relative to the 8 AM dosing (approximately 15 minutes after conducting the IOP measurements). Intraocular pressure was measured by Goldmann applanation tonometry. One eye from each patient was chosen as the study eye and only data for the study eye were used for the efficacy analysis. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Intent-to-Treat (ITT) analysis data set was pre-specified for the comparison of Brinz/Brim to its individual components (Brinz and Brim). | Baseline, Week 6 | 
| Mean Change in Intraocular Pressure (IOP) From Baseline to Each of the Assessment Time Points (8 AM, +2 Hrs, +7 Hrs, and +9 Hrs) at Week 6 - Brinz/Brim, Brinz+Brim | The study drug was instilled at 8 AM and +7 hours relative to the 8 AM dosing (approximately 15 minutes after conducting the IOP measurements). Intraocular pressure was measured by Goldmann applanation tonometry. One eye from each patient was chosen as the study eye and only data for the study eye were used for the efficacy analysis. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Per-Protocol (PP) analysis data set was pre-specified for the comparison of Brinz/Brim to Brinz+Brim. | Baseline, Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Open-Angle Glaucoma, Ocular Hypertension, Brinzolamide, Brimonidine, Intraocular Pressure