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

Phase 2

Completed

Conditions: Ocular Hypertension
Glaucoma

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

Registration Number: NCT02140060

Lead Sponsor: Alcon Research

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 327

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TRAV Z	Travoprost 0.004% ophthalmic solution TRAVATAN Z®	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
TRAV Z + AZOPT	Travoprost 0.004% ophthalmic solution TRAVATAN Z®	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
TRAV Z	Brinzolamide suspension vehicle	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
TravB/Brinz	Dose Level B / Brinzolamide 1% ophthalmic suspension	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
TravC/Brinz	Travoprost solution vehicle	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
AZOPT	Brinzolamide 1% ophthalmic suspension AZOPT®	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
TravA/Brinz	Dose Level A / Brinzolamide 1% ophthalmic suspension	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
TravA/Brinz	Travoprost solution vehicle	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
TravC/Brinz	Dose Level C / Brinzolamide 1% ophthalmic suspension	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
AZOPT	Travoprost solution vehicle	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
TRAV Z + AZOPT	Brinzolamide 1% ophthalmic suspension AZOPT®	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
TravB/Brinz	Travoprost solution vehicle	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

Primary Outcome Measures

Name	Time	Method
Mean IOP at Week 6	Week 6, 8 AM, 10 AM, 12 PM, 4 PM, and 8 PM	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.

Secondary Outcome Measures