<p>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</p>

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 noninferior to BRINZ+BRIM in patients with OAG/OHT. The safety profile of BBFC was similar to that of BRINZ+BRIM.

Evaluation of the Use of Brinzolamide-Brimonidine Fixed Combination in Maximum Medical Therapy

“…Previous studies in the literature reported adverse drug reactions similar to those in our study after BBFC. 7 , 15 , 16 , 17 , 18 , 19 , 20 Similar to our study, Lerner et al 7 , reported that the rate of ocular adverse effects was 11.9% in patients who received maximum medical therapy in the form of BBFC and a beta-blocker/PG analog. In the same study, ocular adverse effects were observed in 7.5% of the control group given the beta-blocker/PG analog combination alone.…”

“…Based on the results of their study, the authors suggested that BBFC is an effective alternative for patients in whom IOP is not adequately controlled with brinzolamide or brimonidine alone, or in patients with contraindications to PG analog and beta-blockers. Similarly, Wang et al 16 compared treatment regimens including BBFC and separate brinzolamide and brimonidine drops together in patients with POAG and OHT and found both treatment regimens to have similar efficacy and safety. Kozobolis et al 17 compared the efficacy of BBFC and a dorzolamide/timolol fixed combination in 44 patients and reported a comparable IOP-lowering effect and safety profile.…”

“…After fixed combination treatment, adverse effects such as ocular surface damage and dry eye associated with the toxic effects of preservatives such as benzalkonium chloride decrease and drug tolerance increases. 15 , 16 …”

“…In previous studies in the literature, it is seen that the majority of patients treated with BBFC are diagnosed with POAG. 15 , 16 , 17 , 18 , 19 In contrast, our study included 48 patients with POAG (52.2%) and 35 patients with PEG (38.0%). BBFC provided effective IOP reduction in both POAG and PEG patients.…”

The Relationship between Central Macular Thickness and Metabolic Parameters Changes in Patients with Non-Proliferative Diabetic Retinopathy

“…In the present study, mean reduction in IOP after 6 weeks of [17]. In the present study, mean IOP reduction at the end of 6 weeks was statistically similar between the Brinzolamide 1% plus Brimonidine 0.2% Fixed Combination (BBFC) therapy and separate concomitant Brinzolamide 1% and Brimonidine 0.2% therapy in patients of POAG and OHT.…”