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