Comparison of the Intraocular Pressure-Lowering Efficacy and Safety of the Brinzolamide/Brimonidine Fixed-Dose Combination versus Concomitant Use of Brinzolamide and Brimonidine for Management of Open-Angle Glaucoma or Ocular Hypertension

Abstract

Objective: To demonstrate that the intraocular pressure (IOP)-lowering efficacy of a twice-daily brinzolamide 10 mg/mL (BRINZ)/brimonidine 2 mg/mL (BRIM) fixed-dose combination (BBFC) was non-inferior to its individual components (BRINZ+BRIM) dosed concomitantly in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Safety was also evaluated.

Methods and analysis: This was a Phase III, multicenter, observer-masked study in patients from China, Russia and Taiwan. Patients aged ≥18 years with a mean IOP ≥21 mmHg and ≤36 mmHg in the same eye after washout of other IOP-lowering medications were included. Eligible patients were randomized (1:1) to receive BBFC or BRIZ+BRIM eye drops twice daily for 3 months. The primary endpoint was the mean change in diurnal IOP (averaged over 09:00, +2 h, and +7 h) from baseline to Month 3. Adverse events (AEs) were recorded throughout the study.

Results: The per-protocol set included 349 patients (BBFC, n=172; BRINZ+BRIM, n=177). The mean±standard deviation diurnal IOP at baseline was 24.6±2.66 mmHg in both groups. At Month 3, the least square mean±standard error change in diurnal IOP from baseline was -7.2±0.34 mmHg and -7.3±0.34 mmHg with BBFC and BRINZ+BRIM, respectively (between-group difference: 0.1 mmHg [95% CI -0.5, 0.7]). In the BBFC and BRINZ+BRIM groups, 53.3% and 55.0% of patients achieved a diurnal IOP <18 mmHg, and 43.2% and 37.4% of patients, respectively, achieved a mean diurnal IOP reduction >30% from baseline at Month 3. Ocular AEs were reported in 28.7% (BBFC) and 22.5% (BRINZ+BRIM) of patients; conjunctival hyperemia was the most frequent ocular AE (BBFC, 6.4%; BRINZ+BRIM, 6.8%). Non-ocular AEs were reported in 32.4% (BBFC) and 30.4% (BRINZ+BRIM) of patients.

Conclusion: The study findings demonstrate that the efficacy of twice-daily BBFC was non-inferior to BRINZ+BRIM in patients with OAG/OHT. The safety profile of BBFC was similar to that of BRINZ+BRIM.

Keywords: brinzolamide/brimonidine fixed-dose combination; intraocular pressure reduction; ocular hypertension; open-angle glaucoma.

Figure 1

Study design. Abbreviations: BBFC, brinzolamide 10 mg/mL/brimonidine 2 mg/mL fixed-dose combination; BID, twice daily; BRINZ+BRIM, brinzolamide 10 mg/mL and brimonidine 2 mg/mL dosed concomitantly; E1, eligibility visit 1; E2, eligibility visit 2; IOP, intraocular pressure.

Figure 2

Patient disposition. Abbreviations: BBFC, brinzolamide 10 mg/mL/brimonidine 2 mg/mL fixed-dose combination; BRINZ+BRIM, brinzolamide 10 mg/mL and brimonidine 2 mg/mL dosed concomitantly; N, total number of patients; n, number of patients.

Figure 3

The mean IOP in the BBFC and BRINZ+BRIM treatment groups by visit and time point (per-protocol set). Abbreviations: BBFC, brinzolamide 10 mg/mL/brimonidine 2 mg/mL fixed-dose combination; BRINZ+BRIM, brinzolamide 10 mg/mL and brimonidine 2 mg/mL dosed concomitantly; IOP, intraocular pressure; n, number of patients; SD, standard deviation.

Figure 4

(A) The mean IOP change from baseline in the BBFC and BRINZ+BRIM treatment groups by visit and time point (per-protocol set). (B) The mean percentage change in IOP from baseline in the BBFC and BRINZ+BRIM treatment groups by visit and time point (per-protocol set). Abbreviations: BBFC, brinzolamide 10 mg/mL/brimonidine 2 mg/mL fixed-dose combination; BRINZ+BRIM, brinzolamide 10 mg/mL and brimonidine 2 mg/mL dosed concomitantly; IOP, intraocular pressure; n, number of patients; SD, standard deviation.