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

Phase 4

Terminated

Conditions: Open-angle Glaucoma
Ocular Hypertension

Interventions: Drug: Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension
Drug: Brinzolamide/brimonidine vehicle
Drug: Travoprost 0.004%/timolol 0.5% solution

Registration Number: NCT02730871

Lead Sponsor: Alcon Research

Brief Summary: 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: 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).

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 173

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vehicle + Duotrav	Travoprost 0.004%/timolol 0.5% solution	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)
Simbrinza + Duotrav	Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension	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)
Simbrinza + Duotrav	Travoprost 0.004%/timolol 0.5% solution	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)
Vehicle + Duotrav	Brinzolamide/brimonidine vehicle	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)

Primary Outcome Measures

Name	Time	Method
Mean Change From Baseline in Diurnal Intraocular Pressure (IOP) (Mean of Changes at 09:00 and 11:00 Time Points) at Week 6	Baseline, 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.

Secondary Outcome Measures

Name	Time	Method
Mean Change From Baseline in IOP (09:00, 11:00) at Week 6	Baseline, 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.
Mean Percentage Change From Baseline in IOP (09:00, 11:00) at Week 6	Baseline, 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.
Mean Diurnal IOP at Week 6	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.
Mean Percentage Change From Baseline in Diurnal IOP at Week 6	Baseline, 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.