6-Week Proof-of-Concept Study of Travoprost/Brinzolamide Ophthalmic Suspension in Subjects With Open-Angle Glaucoma or Ocular Hypertension

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate Travoprost/Brinzolamide fixed combination (Trav/Brinz) administered twice daily as compared to each of its marketed components (TRAVATAN Z® solution and AZOPT® suspension) and to the unfixed combination of TRAVATAN Z® plus AZOPT® in lowering intraocular pressure (IOP).

Detailed Description
-----------------
This study was divided into two phases conducted in sequence. Phase I was the Screening/Eligibility Phase, which included a Screening Visit, followed by two Eligibility Visits. Phase II was the randomized, double-masked, 6-week Treatment Phase which included on-therapy visits at Week 2 and Week 6. Travoprost was administered in 1 of 3 concentration levels (A-C), where A=lowest and C=highest.

Official Title
-----------------
A 6-Week Proof-of-Concept Study Evaluating the Safety and IOP-Lowering Efficacy of Travoprost/Brinzolamide Fixed Combination Ophthalmic Suspension in Subjects With Open-Angle Glaucoma or Ocular Hypertension

Conditions
-----------------
Glaucoma, Ocular Hypertension

Intervention / Treatment
-----------------
* Drug: Dose Level A / Brinzolamide 1% ophthalmic suspension
* Drug: Dose Level B / Brinzolamide 1% ophthalmic suspension
* Drug: Dose Level C / Brinzolamide 1% ophthalmic suspension
* Drug: Brinzolamide 1% ophthalmic suspension AZOPT®
* Drug: Travoprost 0.004% ophthalmic solution TRAVATAN Z®
* Drug: Travoprost solution vehicle
* Drug: Brinzolamide suspension vehicle


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosed with open-angle glaucoma (including open-angle glaucoma with pseudoexfoliation or pigment dispersion) or ocular hypertension; IOP within the protocol-specified range at both the Eligibility 1 and 2 Visits. Mean IOP 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: Woman of childbearing potential who is currently pregnant, intends to become pregnant during the study period, breastfeeding, or not using adequate birth control methods to prevent pregnancy throughout the study; Unable to discontinue all IOP-lowering ocular medication(s) per the appropriate washout schedule prior to the E1 Visit; Chronic, recurrent or severe inflammatory eye disease; Ocular trauma within the past 6 months prior to the Screening Visit; Ocular infection or ocular inflammation within the past 3 months prior to the Screening Visit; Clinically relevant 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, in the opinion of the Investigator, preclude the administration of a topical prostaglandin analogue or topical carbonic anhydrase inhibitor; Intraocular surgery within the past 6 months prior to the Screening Visit; Ocular laser surgery within the past 3 months prior to the Screening Visit; Any abnormality preventing reliable applanation tonometry; Any other conditions including severe illness which would make the subject, in the opinion of the Investigator, unsuitable for the study; History of hepatic or renal disease that would preclude the safe administration of a carbonic anhydrase inhibitor (CAI) in the opinion of the Investigator; Hypersensitivity to prostaglandin analogues, topical or oral CAIs, sulfonamide derivatives, or to any component of the study medications in the opinion of the Investigator; Recent (within 4 weeks of the Eligibility 1 Visit) use of high dose (> 1 g daily) salicylate therapy; Use of any additional topical or systemic ocular hypotensive medication during the study; Concurrent use of glucocorticoids administered by any route; Less than 30 days stable dosing regimen before the Screening Visit of any medications (excluding the IOP-lowering treatments) or substances administered by any route and used on a chronic basis that may affect IOP (ie, β adrenergic blocking agents); Therapy with another investigational agent within 30 days prior to the Screening Visit; Other protocol-specified exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TravA/Brinz<br>Dose Level A / Brinzolamide 1% ophthalmic suspension (fixed combination), 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks | Drug: Dose Level A / Brinzolamide 1% ophthalmic suspension<br>* Fixed combination<br>Drug: Travoprost solution vehicle<br>* Inactive ingredients used for masking purposes<br>|
| Experimental: TravB/Brinz<br>Dose Level B / Brinzolamide 1% ophthalmic suspension (fixed combination), 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks | Drug: Dose Level B / Brinzolamide 1% ophthalmic suspension<br>* Fixed combination<br>Drug: Travoprost solution vehicle<br>* Inactive ingredients used for masking purposes<br>|
| Experimental: TravC/Brinz<br>Dose Level C / Brinzolamide 1% ophthalmic suspension (fixed combination), 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night, for 6 weeks | Drug: Dose Level C / Brinzolamide 1% ophthalmic suspension<br>* Fixed combination<br>Drug: Travoprost solution vehicle<br>* Inactive ingredients used for masking purposes<br>|
| Active Comparator: AZOPT<br>Brinzolamide 1% ophthalmic suspension, 1 drop twice daily in the treated eye(s) morning and night, with travoprost solution vehicle, 1 drop once daily in the treated eye(s) at night for 6 weeks | Drug: Brinzolamide 1% ophthalmic suspension AZOPT®<br> <br> * Other names: AZOPT®;Drug: Travoprost solution vehicle<br>* Inactive ingredients used for masking purposes<br>|
| Active Comparator: TRAV Z<br>Brinzolamide suspension vehicle, 1 drop twice daily in the treated eye(s) morning and night, with travoprost 0.004% ophthalmic solution, 1 drop once daily in the treated eye(s) at night, for 6 weeks | Drug: Travoprost 0.004% ophthalmic solution TRAVATAN Z®<br> <br> * Other names: TRAVATAN Z®;Drug: Brinzolamide suspension vehicle<br>* Inactive ingredients used for masking purposes<br>|
| Active Comparator: TRAV Z + AZOPT<br>Brinzolamide 1% ophthalmic suspension, 1 drop twice daily in the treated eye(s) twice daily morning and night, with travoprost 0.004% ophthalmic solution, 1 drop once daily in the treated eye(s) at night, for 6 weeks | Drug: Brinzolamide 1% ophthalmic suspension AZOPT®<br> <br> * Other names: AZOPT®;Drug: Travoprost 0.004% ophthalmic solution TRAVATAN Z®<br> <br> * Other names: TRAVATAN Z®;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean IOP at Week 6 | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and measured in millimeters of mercury (mmHg). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye (study eye) was used for the analysis. | Week 6, 8 AM, 10 AM, 12 PM, 4 PM, and 8 PM | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ocular, Glaucoma, Hypertension, OAG, POAG, OHT