Combination trial finds less burning with brinzolamide 1% than dorzolamide 2%

Brinzolamide-timolol and dorzolamide-timolol showed similar IOP-lowering efficacy, but side effects were lower with the brinzolamide combo.

COPENHAGEN — Brinzolamide and dorzolamide, when used in conjunction with timolol, had similar effects on intraocular pressure in a study here. However, patients dosed with brinzolamide plus timolol reported fewer adverse events than those dosed with dorzolamide plus timolol, according to John Thygesen, MD, and colleagues.

“The results were as expected from the study design, which primarily explored the statistical equivalence of brinzolamide with dorzolamide on intraocular pressure-lowering efficacy when given in addition to timolol,” Dr. Thygesen said. “Brinzolamide was shown equivalent to dorzolamide throughout the 3 months of the study.”

Dr. Thygesen, one of the main contributors to this trial sponsored by Alcon Research Ltd., noted this is one of the first studies to directly compare Azopt (brinzolamide 2%, Alcon) and Trusopt (dorzolamide 2%, Merck) given in conjunction with Timoptic (timolol 0.5%, Merck).

A double-blind, randomized, controlled parallel group study was conducted at 31 sites in Australia and Europe. Of the 241 patients initially enrolled in the study, 213 patients were eligible for the baseline primary efficacy analysis. Of those, 15 patients were discontinued from the study.

Included in the study were patients with primary open-angle glaucoma or ocular hypertension uncontrolled by timolol 0.5% twice daily. Patients had intraocular pressure (IOP) values between 23 mm Hg and 36 mm Hg in at least one eye before the scheduled morning dose of timolol 0.5% and between 21 mm Hg and 36 mm Hg two hours after the initial morning dose of timolol 0.5%. All patients were assessed at baseline and monthly during 3 months of treatment, Dr. Thygesen said.

The treatments were equivalent in efficacy, Dr. Thygesen said. IOP reductions differed nonsignificantly, by 0.5 mm Hg or less, at all times.

The twice-daily regimen of brinzolamide 1% plus timolol 0.5% reduced morning IOP values by between 14.2% and 21.9% for a period of 3 months, relative to the timolol baseline, Dr. Thygesen said. Likewise, twice-daily dorzolamide 2% plus timolol 0.5% reduced morning IOP by between 14.1% and 21.2% from baseline.

Based on results of the study, Dr. Thygesen also said that “there is no clinical benefit” offered by three-times-daily dosing of brinzolamide 1% plus timolol 0.5%.

Safety profile impressive

“The results were also expected with regards to superiority on the safety profile of brinzolamide 1% as compared to dorzolamide 2%,” Dr. Thygesen said. “Although safety data were analyzed with descriptive statistics — the study was powered to evaluate the efficacy variable — the results show that brinzolamide 1% is better tolerated than dorzolamide 2%.”

A higher incidence of adverse events was associated with dorzolamide monotherapy, according to the study. With timolol added to the therapy regimen, “the overall incidence of patients experiencing adverse events was significantly higher with dorzolamide 2% plus timolol 0.5% than brinzolamide 1% plus timolol 0.5%,” Dr. Thygesen said. Adverse events under the dorzolamide plus timolol regimen were seen in 32.8% of patients versus 14.7% for those patients under the brinzolamide plus timolol treatment, he said.

In addition, significantly more patients complained of ocular discomfort after dorzolamide 2% plus timolol 0.5% (13.1%) than those dosed with brinzolamide 1% plus timolol 0.5% (1.7%). Dr. Thygesen noted that an earlier study had specifically evaluated the comfort of brinzolamide compared with dorzolamide. “The results of this study confirmed the better tolerance of brinzolamide,” Dr. Thygesen said.

Four patients were discontinued from the study because of dorzolamide-related ocular effects relating to local tolerance, Dr. Thygesen said, but none of the brinzolamide patients were discontinued.

Adverse events for patients on the brinzolamide-timolol treatment included ocular discomfort, blurred vision and taste perversion. Patients on dorzolamide-timolol experienced those same adverse events, but also experienced ocular hyperemia, ocular tearing and ocular pruritus.

“Since patients were also receiving timolol in addition to the tested medications, it is sometimes difficult to attribute the causality of an adverse event to the tested substances or to timolol,” said Dr. Thygesen. “However, all conditions being equal, patients receiving brinzolamide 1% plus timolol 0.5% experienced fewer events related to local tolerance than those receiving dorzolamide 2% plus timolol 0.5%.”

For Your Information:

John Thygesen, MD, can be reached at the Department of Ophthalmology, E2061, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark; +(45) 354-53177; Fax: +(45) 354-53270; e-mail: jthygesen@rh.dk.

Alcon Pharmaceuticals, marketers of Azopt, can be reached at 6201 South Freeway, Fort Worth, TX 76134 USA; +(1) 817-551-6828; fax: +(1) 817-241-0677.

Merck & Co., makers of Trusopt and Timoptic, can be reached at 351 North Sumneytown Pike, North Wales, PA 19454 USA; +(1) 267-305-7896; fax: +(1) 267-305-4283.

References:

Michaud J-E, Friren B, et al. Comparison of topical brinzolamide 1% and dorzolamide 2% eye drops given twice daily in addition to timolol 0.5% in patients with primary open-angle glaucoma or ocular hypertension. Am J Ophthalmol. 2001;132:235-243.

Silver LH, the Brinzolamide Comfort Study Group. Ocular comfort of brinzolamide 1.0% ophthalmic suspension compared with dorzolamide 2.0% ophthalmic solution. Results from two multicenter comfort studies. Surv Ophthalmol. 2000;44(4 suppl 2):141-145.