Efficacy and Safety of Brinzolamide/Brimonidine Fixed Combination BID Compared to Brinzolamide BID Plus Brimonidine BID in Subjects With Open-Angle Glaucoma (OAG) or Ocular Hypertension (OHT)

Study Overview
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Brief Summary
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The purpose of this study is to compare the fixed combination (BID) [Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL eyes drops, suspension] to the unfixed combination (BID) [Brinzolamide 10 mg/mL eye drops, suspension plus Brimonidine 2 mg/mL eyes drops, solution] with respect to intraocular pressure (IOP)-lowering efficacy.

Detailed Description
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This study is divided into 2 phases conducted in sequence for a total of 6 visits: Phase I (Screening/Eligibility) which includes a Screening Visit, followed by 2 Eligibility Visits (E1 and E2) and Phase II (Treatment/Follow-up) which includes 3 visits at Week 2, Week 6, and Month 3. Following washout of any IOP-lowering medication, subjects who meet all inclusion/exclusion criteria at both Eligibility visits and had IOP measurements within the specified range during this period will be randomized to Phase II.

Official Title
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Efficacy and Safety of Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL Eye Drops, Suspension Compared to Brinzolamide 10 mg/mL Eye Drops, Suspension Plus Brimonidine 2 mg/mL Eye Drops, Solution in Subjects With Open-Angle Glaucoma or Ocular Hypertension

Conditions
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Open-Angle Glaucoma, Ocular Hypertension

Intervention / Treatment
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* Drug: Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL fixed combination eye drops, suspension
* Drug: Brinzolamide 10 mg/mL eye drops, suspension
* Drug: Brimonidine 2 mg/mL eye drops, solution
* Drug: Vehicle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of open-angle glaucoma or ocular hypertension insufficiently controlled on monotherapy or currently on multiple IOP-lowering medications; Mean IOP measurements within guidelines specified in the protocol. Must not be > 36 mmHg at any time point; Able to understand and sign an informed consent form; Other protocol-specified inclusion criteria may apply. Exclusion Criteria: Women of childbearing potential who are pregnant, test positive for pregnancy, intend to become pregnant during the study period, breast-feeding, or not in agreement to use adequate birth control methods throughout the study; Severe central visual field loss in either eye; Unable to safely discontinue all IOP-lowering ocular medication(s) for a minimum of 5 (± 1) to 28 (± 1) days prior to E1 Visit; Chronic, recurrent or severe inflammatory eye disease; Ocular trauma within the past 6 months; Ocular infection or ocular inflammation within the past 3 months; Clinically significant or progressive retinal disease such as retinal degeneration, diabetic retinopathy, or retinal detachment; Best-corrected visual acuity (BCVA) score worse than 55 ETDRS letters (equivalent to approximately 0.60 logMAR, 20/80 Snellen, or 0.25 decimal); Other ocular pathology (including severe dry eye) that may preclude the administration of α-adrenergic agonist and/or topical carbonic anhydrase inhibitor (CAI); Intraocular surgery within the past 6 months; Ocular laser surgery within the past 3 months; Any abnormality preventing reliable applanation tonometry; Any conditions including severe illness which would make the Subject, in the opinion of the Investigator, unsuitable for the study; History of active, severe, unstable or uncontrolled cardiovascular, cerebrovascular, hepatic, or renal disease that would preclude safe administration of a topical α-adrenergic agonist or CAI; Recent (within 4 weeks of the E1 Visit) use of high-dose (> 1 g daily) salicylate therapy; Current or anticipated treatment with any psychotropic drugs that augment adrenergic response (eg, desipramine, amitriptyline); Concurrent use of monoamine oxidase inhibitors (MAOI); Concurrent use of glucocorticoids administered by any route; Therapy with another investigational agent within 30 days prior to the Screening Visit; Hypersensitivity to α-adrenergic agonist drugs, topical or oral CAIs, sulfonamide derivatives, or to any component of the study medications; Less than 30 days stable dosing regimen before the Screening Visit of any medications (excluding IOP-lowering treatments) or substances administered by any route and used on a chronic basis that may affect IOP, including but not limited to β-adrenergic blocking agents; Use of any additional topical or systemic ocular hypotensive medication during the study; Other protocol-specified exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 95 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brinz/Brim<br>Vehicle solution, 1 drop, followed by Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL fixed combination eye drops, suspension, 1 drop, administered at least 5 minutes apart in the treated eye(s) twice daily (BID) for 3 months | Drug: Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL fixed combination eye drops, suspension<br> <br> Drug: Vehicle<br>* Inactive ingredients used as a placebo for masking purposes<br>|
| Active Comparator: Brinz+Brim<br>Brimonidine 2 mg/mL eye drops, solution, 1 drop, followed by Brinzolamide 10 mg/mL eye drops, suspension, 1 drop, administered at least 5 minutes apart in the treated eye(s) BID for 3 months | Drug: Brinzolamide 10 mg/mL eye drops, suspension<br> <br> * Other names: AZOPT™;Drug: Brimonidine 2 mg/mL eye drops, solution<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Diurnal IOP Change From Baseline at Month 3 | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in mmHg. Diurnal IOP was defined as the average of the three timepoints measured: 9 AM, +2 Hrs and +7Hrs. Baseline was the average of the values for 2 eligibility visits. If one of the values was missing, the other non-missing value was taken as the baseline. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates greater improvement, ie, a reduction of IOP. Only one eye (study eye) contributed to the analysis. | Baseline (Day 0), Month 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OAG, OHT