Phase 3 Randomized 3-Month Trial with an Ongoing 3-Month Safety Extension of Fixed-Combination Brinzolamide 1%/Brimonidine 0.2%

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.

Combination of brinzolamide and brimonidine for glaucoma and ocular hypertension: critical appraisal and patient focus

“…The incidence of ocular hyperemia continued to be higher in the brimonidine group (3.8%) than the BBFC (2.7%) or brinzolamide (0.4%) groups after 6 months 56. In the two Phase III clinical trials, discontinuations because of nonserious TRAEs were more common with BBFC (up to 11.3%) than with brinzolamide (up to 2.1%) or brimonidine (up to 9.4%) 53,54. The slightly greater occurrence of some TRAEs and TRAE-related discontinuations with BBFC in these studies may be attributable to exposure to multiple therapeutic agents (ie, brinzolamide and brimonidine) versus monotherapy.…”

“…The occurrence of blurred vision with BBFC and brinzolamide in some patients is unsurprising given that these medications are administered as ophthalmic suspensions. In contrast, the most frequently reported ocular TRAEs with brimonidine at 3 months were conjunctivitis (3.0%), dry eye (0.4%–2.7%), eye irritation (1.8%–2.6%), and ocular hyperemia (2.6%–4.1%) 53,54. In both trials, the incidence of ocular hyperemia was more prevalent with brimonidine (2.6%–4.1%) than BBFC (0.9%–3.3%) or brinzolamide (0.4%–0.9%) at 3 months 53,54.…”

“…53 Mean IOP reductions from baseline and percentage change in IOP from baseline were also greater with BBFC (5.7–8.8 mmHg; percentage reduction, 24.1%–34.9%) than with brinzolamide (4.1–6.2 mmHg; percentage reduction, 16.9%–22.6%) or brimonidine (3.5–6.5 mmHg; percentage reduction, 14.3%–25.8%) 53. Similar results were observed in a separate randomized, double-masked Phase III trial with a 3-month safety extension (LS mean IOP at 3 months: BBFC, 17.2–21.1 mmHg; brinzolamide, 20.4–22.0 mmHg, P ≤0.005 versus [vs] BBFC; brimonidine, 18.9–23.2 mmHg, P <0.0001 vs BBFC; Figure 2) and a pooled analysis of both Phase III trials (LS mean IOP at 3 months: BBFC, 17.1–20.8 mmHg; brinzolamide, 20.2–21.8 mmHg, P <0.0001 vs BBFC; brimonidine, 18.8–23.2 mmHg, P <0.0001 vs BBFC) 54,55. Greater reductions in mean IOP with BBFC compared with brinzolamide or brimonidine were observed at week 2 (the first post baseline evaluation day) in both Phase III trials53,54 and continued for up to 6 months (mean reductions from baseline to month 6: 4.9–8.0 mmHg with BBFC, 4.1–5.8 mmHg with brinzolamide, and 3.0–6.3 mmHg with brimonidine) 56.…”

“…Similar results were observed in a separate randomized, double-masked Phase III trial with a 3-month safety extension (LS mean IOP at 3 months: BBFC, 17.2–21.1 mmHg; brinzolamide, 20.4–22.0 mmHg, P ≤0.005 versus [vs] BBFC; brimonidine, 18.9–23.2 mmHg, P <0.0001 vs BBFC; Figure 2) and a pooled analysis of both Phase III trials (LS mean IOP at 3 months: BBFC, 17.1–20.8 mmHg; brinzolamide, 20.2–21.8 mmHg, P <0.0001 vs BBFC; brimonidine, 18.8–23.2 mmHg, P <0.0001 vs BBFC) 54,55. Greater reductions in mean IOP with BBFC compared with brinzolamide or brimonidine were observed at week 2 (the first post baseline evaluation day) in both Phase III trials53,54 and continued for up to 6 months (mean reductions from baseline to month 6: 4.9–8.0 mmHg with BBFC, 4.1–5.8 mmHg with brinzolamide, and 3.0–6.3 mmHg with brimonidine) 56. Thus, the therapeutic benefit of BBFC occurs shortly after initial administration (ie, within the first 2 weeks) and continues for up to 6 months.…”

Early Clinical Experiences with Brinzolamide/Brimonidine Fixed Combination in Open-angle Glaucoma and Ocular Hypertension

“…Registration of BBFC with the FDA for three-times daily eye drop dosing for glaucoma treatment was supported by three phase III trials (n=660-690) [25][26][27] (Table 4). A combined analysis 28 of two of the phase III trials showed that after 3 months treatment, patients receiving BBFC mean IOP levels were significantly lower than in patients receiving brinzolamide or brimonidine alone (p<0.0001) at four daily time points (08.00, 10.00, 15.00 and 17.00 hours) (see Figure 3).…”