Safety and Efficacy of SIMBRINZA® BID as an Adjunctive to DUOTRAV®

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the additive intraocular pressure (IOP) lowering effect of Brinzolamide 1%/Brimonidine 0.2% (SIMBRINZA®) dosed twice daily (BID) when added to Travoprost 0.004%/Timolol 0.5% (DUOTRAV®) in subjects with open-angle glaucoma or ocular hypertension.

Detailed Description
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This study is divided into 2 sequential phases for a total of 5 visits. Phase I of the study is the open-labeled Screening/Eligibility Phase, which includes a Screening Visit followed by 2 Eligibility Visits. Phase II of the study is the randomized, double-masked Treatment Phase, which includes 2 on-therapy visits: Visit 4 (at Week 2) and Visit 5 (Week 6, Exit Visit).

Official Title
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Safety and Efficacy With Twice Daily Brinzolamide 1%/Brimonidine 0.2% (SIMBRINZA®) as an Adjunctive Therapy to Travoprost 0.004%/Timolol 0.5% (DUOTRAV®)

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/brimonidine vehicle
* Drug: Travoprost 0.004%/timolol 0.5% solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of open-angle glaucoma (including pseudoexfoliation or pigment dispersion glaucoma) or ocular hypertension. Currently on treatment with Travoprost 0.004%/Timolol 0.5% prescribed as approved in the country, on morning or evening dosing for at least 28 days prior to screening, and in the opinion of the Investigator may benefit from further IOP lowering. Mean IOP measurements at both the Eligibility 1 and Eligibility 2 visits, in at least 1 eye (the same eye(s) ≥ 19 and ≤ 28 mmHg at 09:00 while on a Travoprost 0.004%/ Timolol 0.5% solution. Able to understand and sign an informed consent form that has been approved by an Institutional Review Board/Ethics Committee. Willing and able to attend all study visits. Exclusion Criteria: Women of childbearing potential: not postmenopausal for at least 1 year or less than 6 weeks since sterilization, currently pregnant; have a positive result on the urine pregnancy test at Screening; intend to become pregnant during the study period; breast-feeding; or not in agreement to use adequate birth control methods to prevent pregnancy throughout the study. Mean IOP > 28 mmHg at any time point in either eye during the Screening/Eligibility Phase. Any form of glaucoma other than open-angle glaucoma or ocular hypertension. Severe central visual field loss in either eye. Chronic, recurrent or severe inflammatory eye disease in either eye. Ocular trauma in either eye within the past 6 months prior to the Screening visit. Ocular infection or ocular inflammation in either eye within the past 3 months prior to the Screening visit. Retinal degeneration, diabetic retinopathy, or retinal detachment in either eye. Best-corrected visual acuity score worse than 55 ETDRS letters (equivalent to approximately 20/80 Snellen, 0.60 logMAR or 0.25 decimal) in either eye. Other ocular pathology (including severe dry eye) in either eye that may, in the opinion of the Investigator, preclude the safe administration of any study medication. Intraocular surgery in either eye within the past 6 months prior to the Screening visit. Ocular laser surgery in either eye within the past 3 months prior to the Screening visit. Any other condition including severe illness which would make the subject, in the opinion of the Investigator, unsuitable for the study. Asthma, history of asthma, or severe chronic obstructive pulmonary disease.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simbrinza + Duotrav<br>Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00 hrs) plus travoprost 0.004%/timolol 0.5% solution, 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for 42 days (Treatment Phase) | Drug: Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension<br> <br> * Other names: SIMBRINZA® suspension;Drug: Travoprost 0.004%/timolol 0.5% solution<br>* 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for up to 10 days during the Screening/Eligibility Phase and 42 days during the Treatment Phase<br>* Other names: DUOTRAV®;|
| Placebo Comparator: Vehicle + Duotrav<br>Brinzolamide/brimonidine vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00 hrs) plus travoprost 0.004%/timolol 0.5% solution, 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for 42 days (Treatment Phase) | Drug: Brinzolamide/brimonidine vehicle<br>* Inactive ingredients used as placebo comparator<br>Drug: Travoprost 0.004%/timolol 0.5% solution<br>* 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for up to 10 days during the Screening/Eligibility Phase and 42 days during the Treatment Phase<br>* Other names: DUOTRAV®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Diurnal Intraocular Pressure (IOP) (Mean of Changes at 09:00 and 11:00 Time Points) at Week 6 | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry. Diurnal IOP change was defined as the average of the two changes from baseline (timepoints 9 AM, 11 AM). A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) was used for the analyses. | Baseline, Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Diurnal IOP at Week 6 | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry. Diurnal IOP was defined as the average of the two time points measured (9 AM, 11 AM). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Only one eye (study eye) was used for the analyses. | Week 6 | 
| Mean Percentage Change From Baseline in Diurnal IOP at Week 6 | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry. Diurnal IOP percentage change was defined as the average of the two changes from baseline (timepoints 9 AM, 11 AM). A more negative percentage change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) was used for the analyses. | Baseline, Week 6 | 
| Mean Change From Baseline in IOP (09:00, 11:00) at Week 6 | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) was used for the analyses. | Baseline, Week 6 | 
| Mean Percentage Change From Baseline in IOP (09:00, 11:00) at Week 6 | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry. A more negative percentage change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) was used for the analyses. | Baseline, Week 6 |