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

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

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).

Study Overview

• Status: Completed
• Conditions: Ocular Hypertension; Glaucoma
• Intervention / Treatment: Drug: Dose Level A / Brinzolamide 1% ophthalmic suspension; Drug: Travoprost solution vehicle; 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: Brinzolamide suspension vehicle

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.

• Study Type: Interventional
• Enrollment (Actual): 327
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TravA/Brinz; 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; Fixed combination; Drug: Travoprost solution vehicle; Inactive ingredients used for masking purposes
Experimental: TravB/Brinz; 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: Travoprost solution vehicle; Inactive ingredients used for masking purposes; Drug: Dose Level B / Brinzolamide 1% ophthalmic suspension; Fixed combination
Experimental: TravC/Brinz; 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: Travoprost solution vehicle; Inactive ingredients used for masking purposes; Drug: Dose Level C / Brinzolamide 1% ophthalmic suspension; Fixed combination
Active Comparator: 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	Drug: Travoprost solution vehicle; Inactive ingredients used for masking purposes; Drug: Brinzolamide 1% ophthalmic suspension AZOPT®; Other Names: AZOPT®
Active Comparator: TRAV 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	Drug: Travoprost 0.004% ophthalmic solution TRAVATAN Z®; Other Names: TRAVATAN Z®; Drug: Brinzolamide suspension vehicle; Inactive ingredients used for masking purposes
Active Comparator: TRAV Z + 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	Drug: Brinzolamide 1% ophthalmic suspension AZOPT®; Other Names: AZOPT®; Drug: Travoprost 0.004% ophthalmic solution TRAVATAN Z®; 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

Collaborators and Investigators

• Sponsor: Alcon Research
• Investigators: Study Director: Sr. Clinical Manager, GCRA, Pharma, Alcon Research

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: May 14, 2014
• First Submitted That Met QC Criteria: May 15, 2014
• First Posted (Estimate): May 16, 2014

Study Record Updates

• Last Update Posted (Estimate): December 29, 2015
• Last Update Submitted That Met QC Criteria: November 24, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: POAG; Hypertension; Glaucoma; OAG; OHT; Ocular
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Ophthalmic Solutions; Pharmaceutical Solutions; Travoprost; Brinzolamide
• Other Study ID Numbers: C-14-003