ABSTRACT
BACKGROUND: The objective of this study was to examine the safety and intraocular pressure (IOP)-lowering efficacy of a fixed combination of brinzolamide 1% + brimonidine 0.2% (BBFC) after six months of treatment in patients with open-angle glaucoma or ocular hypertension. METHODS: This was a randomized, multicenter, double-masked, three-month, three-arm contribution-of-elements study with a three-month safety extension. Patients were randomly assigned 1:1:1 to treatment with BBFC, brinzolamide 1%, or brimonidine 0.2% after a washout period. Patients dosed their study medications three times daily at 8 am, 3 pm, and 10 pm for six months. Patients returned for visits at two weeks, six weeks, three months, and six months. IOP measurements were used to assess efficacy. Safety assessments were adverse events, corrected distance visual acuity, slit-lamp biomicroscopy, pachymetry, perimetry, fundus parameters, and cardiac parameters. RESULTS: A total of 690 patients were randomized. Six-month mean IOP values were similar to those at three months, when the mean IOP in patients treated with BBFC was significantly lower than that of either monotherapy group. A total of 175 patients experienced at least one treatment-related adverse event (BBFC, 33.0%; brinzolamide, 18.8%; brimonidine, 24.7%), eight of which were severe, and five resulted in discontinuation. Seventy-seven patients discontinued participation due to treatment-related adverse events (BBFC, 17.2%; brinzolamide, 2.1%; brimonidine, 14.5%). There were 21 serious adverse events (n = 7 in each group), none of which was related to treatment. Resting mean pulse and blood pressure with BBFC were similar to those with brimonidine, demonstrating modest, clinically insignificant decreases. No new or increased risks were identified with use of BBFC relative to either monotherapy. CONCLUSION: This study showed that, after six months of treatment, the safety profile of BBFC was similar to that of its individual components and its IOP-lowering activity was similar to its efficacy at three months, when it was superior to both brinzolamide 1% alone and brimonidine 0.2% alone.
ABSTRACT
PURPOSE: This study compared the intraocular pressure (IOP)-lowering efficacy of fixed-combination brinzolamide 1%/brimonidine 0.2% (BBFC) with that of its component medications, brinzolamide and brimonidine, in patients with open-angle glaucoma or ocular hypertension. PATIENTS AND METHODS: In this phase 3, multicenter, double-masked, parallel-group, 3-month study with a 3-month safety extension, eligible patients were randomized 1:1:1 to treatment with BBFC, brinzolamide, or brimonidine thrice daily after a washout period, during which any IOP-lowering medications were discontinued. The primary objectives of this study were to determine whether the IOP-lowering efficacy of BBFC was superior to that of brinzolamide alone and, separately, of brimonidine alone. IOP was assessed at 8:00 AM, 10:00 AM, 3:00 PM, and 5:00 PM at 2 weeks, 6 weeks, and 3 months after study drug initiation. RESULTS: A total of 690 patients were enrolled in the study, and 615 completed the 3-month visit. Baseline mean IOP levels were similar among the 3 treatment groups at each of the 4 time points assessed. At the 3-month primary endpoint, mean IOP of the BBFC group was significantly lower than that of either the brinzolamide group or the brimonidine group (P≤0.005) across all time points. At the 2- and 6-week supportive endpoints, mean IOP of the BBFC group was significantly lower at all time points than the mean IOP of either the brinzolamide group (P≤0.01) or the brimonidine group (P<0.0001). A total of 143 patients experienced at least 1 treatment-related adverse event (AE; BBFC group, n=58, 26.2%; brinzolamide group, n=44, 18.8%; brimonidine group, n=41, 17.4%), the majority of which were ocular AEs. CONCLUSIONS: This study demonstrated that BBFC has significantly superior IOP-lowering activity compared with either brinzolamide 1% or brimonidine 0.2% in patients with open-angle glaucoma or ocular hypertension while providing a safety profile which is consistent with that of the individual components.
