Randomized trial of brinzolamide/brimonidine versus brinzolamide plus brimonidine for open-angle glaucoma or ocular hypertension

Abstract

Introduction: Fixed-combination intraocular pressure (IOP)-lowering medications simplify treatment regimens for patients requiring 2 ocular hypotensive agents to maintain sufficiently low IOP. The aim of this study was to evaluate the safety and efficacy of fixed-combination brinzolamide 1%/brimonidine 0.2% (BBFC) versus concomitant administration of brinzolamide 1% plus brimonidine 0.2% (BRINZ + BRIM) in patients with open-angle glaucoma or ocular hypertension.

Methods: This was a prospective, phase 3, multicenter, double-masked, 6-month trial. Patients who had insufficient IOP control with monotherapy or who were receiving 2 IOP-lowering medications were randomized 1:1 to receive twice-daily BBFC or BRINZ + BRIM. IOP was assessed at 9 a.m. and 11 a.m. during week 2, week 6, month 3, and month 6 visits. The primary efficacy endpoint was mean diurnal IOP change from baseline to month 3; noninferiority was concluded if the upper limit of the 95% CI of the between-group difference was <1.5 mmHg. Supportive endpoints included mean IOP, IOP change from baseline, and percentage of patients with IOP <18 mmHg. Adverse events were recorded.

Results: The mean diurnal IOP change from baseline with BBFC (least squares mean ± standard error -8.5 ± 0.16 mmHg) was noninferior to that with BRINZ + BRIM (-8.3 ± 0.16 mmHg; mean difference -0.1 mmHg; 95% CI -0.5 to 0.2 mmHg). The upper limits of the 95% CIs were <1.5 mmHg at all time points. Decreases from baseline >8 mmHg were observed for least squares mean diurnal IOP in both groups as early as week 2 and continued to the end of the study. The results of all other supportive endpoints were similar to the primary efficacy endpoint. The most common ocular adverse drug reactions were hyperemia of the eye (reported as ocular or conjunctival hyperemia), visual disturbances, ocular allergic reactions, and ocular discomfort. Common systemic adverse drug reactions included dysgeusia, oral dryness, and fatigue/drowsiness.

Conclusion: Brinzolamide 1%/brimonidine 0.2% fixed combination was as well tolerated and effective as concomitant therapy with its components. BBFC reduces treatment burden in patients who require multiple IOP-lowering medications.

Trial registration: ClinicalTrials.gov NCT01309204.

Figures

Fig. 1

Patient disposition. Percentages reflect number of patients randomized to treatment for each group. Asterisk indicates patients analyzed according to treatment received; two patients were randomized to receive BRINZ + BRIM but actually received BBFC. AE adverse event, BBFC brinzolamide 1%/brimonidine 0.2% fixed combination, BRINZ + BRIM concomitant unfixed brinzolamide 1% and brimonidine 0.2%, IOP intraocular pressure, ITT intent-to-treat, PP per-protocol

Fig. 2

LS mean changes in diurnal IOP (i.e., average of IOP at 9 a.m. and 11 a.m.) from baseline (per-protocol population). Error bars represent standard errors. LS mean between-group differences and 95% CIs for the primary efficacy endpoint (month 3) and supportive efficacy endpoints (week 2 and month 6) are provided. BBFC brinzolamide 1%/brimonidine 0.2% fixed combination, BRINZ + BRIM concomitant unfixed brinzolamide 1% and brimonidine 0.2%, IOP intraocular pressure, LS least squares