Brinzolamide/brimonidine demonstrates broad efficacy in subgroup analyses

February 1, 2015

The protocols for the pivotal trials establishing the efficacy of the brinzolamide 1%/brimonidine 0.2% fixed combination included pre-planned analyses of subgroups defined by IOP and demographic characteristics.

 

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The protocols for the pivotal trials establishing the efficacy of the brinzolamide 1%/brimonidine 0.2% fixed combination included pre-planned analyses of subgroups defined by IOP and demographic characteristics.

 

 

By Cheryl Guttman Krader; Reviewed by Tony Realini, MD, MPH

Morgantown, WV-Results from pre-planned subgroup analyses of IOP outcomes in the brinzolamide 1%/brimonidine 0.2% fixed combination (Simbrinza, Alcon Laboratories) pivotal trial demonstrate the product has broad applicability for patients with ocular hypertension and open-angle glaucoma, said Tony Realini, MD, MPH.

“We are fortunate that we have so many options for IOP reduction at this time, and I welcome the introduction of all new products,” said Dr. Realini, associate professor of ophthalmology and director, glaucoma fellowship, West Virginia University Health Sciences Center, Morgantown, WV. “Some transform the therapeutic landscape and some are niche products.

“I have found that every product is the ideal treatment for some of my patients, and the brinzolamide/brimonidine fixed combination expands our options,” he added.

The brinzolamide/brimonidine fixed combination pivotal trial program comprised two parallel-arm, double-masked studies that enrolled a total of 690 patients with open-angle glaucoma or ocular hypertension. Patients were randomly assigned 1:1:1 into three groups to receive the fixed combination or its components as monotherapy.

IOP measurements were obtained at 8 a.m. (trough), 10 a.m., 3 p.m., and 5 p.m. The primary endpoint visit was at 3 months, and the analyses of those data showed statistical superiority of the brinzolamide/fixed combination to its components in lowering IOP at all four time points.

The prespecified subgroup analyses investigated potential variations in IOP responses depending on baseline IOP (24 to 27, 38 to 36 mm Hg), age (<65, >65, 65-75, 75 to 85 years), gender, and ethnicity (Caucasian, African American, and Hispanic).

Result for the overall population showed that at the 3-month visit, mean IOP across the four time points ranged from 16.5 to 20.2 mm Hg in the brinzolamide/brimonidine fixed combination group, 19.5 to 21.2 mm Hg in eyes treated with brinzolamide, and 18.0 to 22.5 mm Hg in the brimonidine group. For all four time points, the difference between the fixed combination group and both the brinzolamide and brimonidine group was statistically significant.

The results of the subgroup analyses showed that the IOP-lowering effect of the brinzolamide/brimonidine fixed combination remained superior to that of its components at all time points across all subgroups.

In addition, comparisons of the IOP-lowering effect of the brinzolamide/brimonidine fixed combination were undertaken between subgroups within each category, and those results showed it had the same efficacy profile regardless of baseline IOP, age, gender, and ethnicity.

Novel benefits

The brinzolamide/brimonidine fixed combination brings value to the medical armamentarium as the first fixed combination IOP-lowering product without a beta-blocker, Dr. Realini noted.

“Now patients with contraindications to beta-blockers can enjoy the benefits of fixed combination therapy,” he said.

“In addition, the [product] offers a fixed combination in which both agents can be expected to provide optimal IOP reduction in patients on systemic beta-blocker therapy in whom topical beta-blockers are less effective in lowering IOP,” he said.

Dr. Realini also observed that unlike beta-blockers, both brinzolamide and brimonidine provide additive IOP reduction when used in conjunction with a prostaglandin analogue.

“The brinzolamide/brimonidine fixed combination represents the first fixed combination containing two agents both known to provide additive IOP reduction when used in conjunction with a PGA,” he said.

 

Tony Realini, MD, MPH

E: realinia@wvuhealthcare.com

Dr. Realini is a consultant to Alcon Laboratories and receives research support from Lumenis.