Noninferiority Study Comparing Latanoprost 0.005% Without Versus With Benzalkonium Chloride in Open-Angle Glaucoma or Ocular Hypertension.

OBJECTIVES: To evaluate the noninferiority of intraocular pressure (IOP)-lowering latanoprost without benzalkonium chloride (BAK) versus latanoprost with BAK (for treatment of open-angle glaucoma or ocular hypertension). METHODS: Overall, 578 patients were randomized 1:1 to latanoprost without BAK or latanoprost with BAK once daily in the affected eye(s) for 12 weeks. The primary efficacy endpoint was IOP, measured on days 0, 7, 28, 56, and 84 (8 am, 10 am, and 4 pm). Noninferiority was established if the following criteria were met: 95% confidence interval (CI) of the mean difference between treatments included 0 mm Hg for all time points (N1), 95% CI upper limit less than 1.5 mm Hg (N2), and less than 1 mm Hg for≥7 of 12 time points (N3). Primary efficacy analysis was performed on the intent-to-treat population. Safety measurements included ocular and systemic adverse event (AE). RESULTS: The 95% CI included 0 mm Hg for 7/12 time points (N1), 95% CI upper limit was less than 1.5 mm Hg for 12/12 time points (N2), and less than 1.0 mm Hg for 4/7 time points (N3). AEs were mild and similarly distributed between groups. CONCLUSIONS: Latanoprost without BAK did not meet two of three criteria for noninferiority and showed a similar safety profile relative to latanoprost with BAK.

A Randomized Trial of Fixed-Dose Combination Brinzolamide 1%/Brimonidine 0.2% as Adjunctive Therapy to Travoprost 0.004.

PURPOSE: To evaluate the safety and efficacy of adding fixed-combination brinzolamide 1%/brimonidine 0.2% (BBFC) as adjunctive therapy to travoprost 0.004% (TRAV) in patients with open-angle glaucoma or ocular hypertension. DESIGN: Multicenter, randomized, double-masked, parallel-group phase 4 clinical trial. METHODS: setting: Multicenter; 32 sites in the United States. PATIENT POPULATION: Total of 233 patients with open-angle glaucoma or ocular hypertension and with mean intraocular pressure (IOP) ≥21 mm Hg and <32 mm Hg while receiving once-daily TRAV monotherapy. INTERVENTION: Masked BBFC or vehicle (3 times daily) adjunctive to TRAV for 6 weeks. MAIN OUTCOME MEASURE: Mean diurnal IOP averaged over 8 AM, 10 AM, 3 PM, and 5 PM time points at week 6. Superiority of BBFC+TRAV over vehicle+TRAV was based on statistical significance of a treatment difference favoring BBFC+TRAV. RESULTS: Mean diurnal IOP at week 6 (least squares mean ± standard error) was 17.6 ± 0.4 mm Hg and 20.7 ± 0.4 mm Hg in the BBFC+TRAV and vehicle+TRAV groups, respectively (between-group difference, -3.2 ± 0.5 mm Hg; P < .0001). Superiority of BBFC+TRAV over vehicle+TRAV was established. Mean and percent diurnal IOP change from baseline were significantly greater with BBFC+TRAV compared with vehicle+TRAV (P < .0001 for both). Conjunctival hyperemia was the most common treatment-related adverse event in either group (BBFC+TRAV, 12.8%; vehicle+TRAV, 6.0%). CONCLUSIONS: Adjunctive treatment with BBFC added to TRAV resulted in lower mean diurnal IOP after 6 weeks of treatment compared with vehicle added to TRAV; this difference was both statistically and clinically significant.

Six-month results from a Phase III randomized trial of fixed-combination brinzolamide 1% + brimonidine 0.2% versus brinzolamide or brimonidine monotherapy in glaucoma or ocular hypertension.

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.

Phase 3 randomized 3-month trial with an ongoing 3-month safety extension of fixed-combination brinzolamide 1%/brimonidine 0.2%.

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.