Efficacy and Safety of Brinzolamide/Brimonidine Fixed Combination BID Compared to Brinzolamide BID Plus Brimonidine BID in Subjects With Open-Angle Glaucoma (OAG) or Ocular Hypertension (OHT)

Efficacy and Safety of Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL Eye Drops, Suspension Compared to Brinzolamide 10 mg/mL Eye Drops, Suspension Plus Brimonidine 2 mg/mL Eye Drops, Solution in Subjects With Open-Angle Glaucoma or Ocular Hypertension

The purpose of this study is to compare the fixed combination (BID) [Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL eyes drops, suspension] to the unfixed combination (BID) [Brinzolamide 10 mg/mL eye drops, suspension plus Brimonidine 2 mg/mL eyes drops, solution] with respect to intraocular pressure (IOP)-lowering efficacy.

Study Overview

• Status: Completed
• Conditions: Ocular Hypertension; Open-Angle Glaucoma
• Intervention / Treatment: Drug: Vehicle; Drug: Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL fixed combination eye drops, suspension; Drug: Brinzolamide 10 mg/mL eye drops, suspension; Drug: Brimonidine 2 mg/mL eye drops, solution

Detailed Description

This study is divided into 2 phases conducted in sequence for a total of 6 visits: Phase I (Screening/Eligibility) which includes a Screening Visit, followed by 2 Eligibility Visits (E1 and E2) and Phase II (Treatment/Follow-up) which includes 3 visits at Week 2, Week 6, and Month 3. Following washout of any IOP-lowering medication, subjects who meet all inclusion/exclusion criteria at both Eligibility visits and had IOP measurements within the specified range during this period will be randomized to Phase II.

• Study Type: Interventional
• Enrollment (Actual): 493
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of open-angle glaucoma or ocular hypertension insufficiently controlled on monotherapy or currently on multiple IOP-lowering medications;
• Mean IOP measurements within guidelines specified in the protocol. 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:

• Women of childbearing potential who are pregnant, test positive for pregnancy, intend to become pregnant during the study period, breast-feeding, or not in agreement to use adequate birth control methods throughout the study;
• Severe central visual field loss in either eye;
• Unable to safely discontinue all IOP-lowering ocular medication(s) for a minimum of 5 (± 1) to 28 (± 1) days prior to E1 Visit;
• Chronic, recurrent or severe inflammatory eye disease;
• Ocular trauma within the past 6 months;
• Ocular infection or ocular inflammation within the past 3 months;
• Clinically significant 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 preclude the administration of α-adrenergic agonist and/or topical carbonic anhydrase inhibitor (CAI);
• Intraocular surgery within the past 6 months;
• Ocular laser surgery within the past 3 months;
• Any abnormality preventing reliable applanation tonometry;
• Any conditions including severe illness which would make the Subject, in the opinion of the Investigator, unsuitable for the study;
• History of active, severe, unstable or uncontrolled cardiovascular, cerebrovascular, hepatic, or renal disease that would preclude safe administration of a topical α-adrenergic agonist or CAI;
• Recent (within 4 weeks of the E1 Visit) use of high-dose (> 1 g daily) salicylate therapy;
• Current or anticipated treatment with any psychotropic drugs that augment adrenergic response (eg, desipramine, amitriptyline);
• Concurrent use of monoamine oxidase inhibitors (MAOI);
• Concurrent use of glucocorticoids administered by any route;
• Therapy with another investigational agent within 30 days prior to the Screening Visit;
• Hypersensitivity to α-adrenergic agonist drugs, topical or oral CAIs, sulfonamide derivatives, or to any component of the study medications;
• Less than 30 days stable dosing regimen before the Screening Visit of any medications (excluding IOP-lowering treatments) or substances administered by any route and used on a chronic basis that may affect IOP, including but not limited to β-adrenergic blocking agents;
• Use of any additional topical or systemic ocular hypotensive medication during the study;
• 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Brinz/Brim; Vehicle solution, 1 drop, followed by Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL fixed combination eye drops, suspension, 1 drop, administered at least 5 minutes apart in the treated eye(s) twice daily (BID) for 3 months	Drug: Vehicle; Inactive ingredients used as a placebo for masking purposes; Drug: Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL fixed combination eye drops, suspension
Active Comparator: Brinz+Brim; Brimonidine 2 mg/mL eye drops, solution, 1 drop, followed by Brinzolamide 10 mg/mL eye drops, suspension, 1 drop, administered at least 5 minutes apart in the treated eye(s) BID for 3 months	Drug: Brinzolamide 10 mg/mL eye drops, suspension; Other Names: AZOPT™; Drug: Brimonidine 2 mg/mL eye drops, solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Diurnal IOP Change From Baseline at Month 3	IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in mmHg. Diurnal IOP was defined as the average of the three timepoints measured: 9 AM, +2 Hrs and +7Hrs. Baseline was the average of the values for 2 eligibility visits. If one of the values was missing, the other non-missing value was taken as the baseline. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates greater improvement, ie, a reduction of IOP. Only one eye (study eye) contributed to the analysis.	Baseline (Day 0), Month 3

Collaborators and Investigators

• Sponsor: Alcon Research
• Investigators: Study Director: Clinical Trial Management, Asia, Alcon, A Novartis Division

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2015
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: January 13, 2015
• First Submitted That Met QC Criteria: January 13, 2015
• First Posted (Estimate): January 15, 2015

Study Record Updates

• Last Update Posted (Actual): July 2, 2018
• Last Update Submitted That Met QC Criteria: May 31, 2018
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: OAG; OHT
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Eye Diseases; Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Carbonic Anhydrase Inhibitors; Pharmaceutical Solutions; Brimonidine Tartrate; Ophthalmic Solutions; Brinzolamide
• Other Study ID Numbers: C-13-013