Original Articles
The long-term safety and efficacy of brinzolamide 1.0% (Azopt) in patients with primary open-angle glaucoma or ocular hypertension

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Abstract

PURPOSE: Oral carbonic anhydrase inhibitors used to treat glaucoma have significant systemic side effects. Brinzolamide 1.0%, a new topical ocular carbonic anhydrase inhibitor, is effective apparently without significant systemic side effects. This study was performed to establish the long-term safety and efficacy of brinzolamide 1.0% two and three times daily for primary open-angle glaucoma and ocular hypertension.

METHODS: An 18-month, multicenter, double-masked, parallel, controlled study was conducted. Patients were randomized to brinzolamide two or three times daily or timolol 0.5% twice daily in a 2:2:1 ratio (n = 150, 153, and 75, respectively). Intraocular pressure was measured at 8:00 am at eligibility and months 1, 3, 6, 9, 12, 15, and 18. Efficacy was based on intraocular pressure reduction from baseline. Safety was also evaluated.

RESULTS: All regimens produced clinically relevant and statistically significant (P < .05) intraocular pressure reductions from baseline. Mean changes in intraocular pressure trough measurements ranged from −2.7 to −3.9 mm Hg with brinzolamide twice-daily dosing and −2.8 to −3.8 mm Hg three times daily dosing compared with −4.7 to −5.6 mm Hg with timolol. The intraocular pressure reductions with brinzolamide two and three times daily were clinically and statistically equivalent. One hundred forty-four patients were discontinued from the study after randomization with the most common reasons being the occurrence of an adverse event (46), inadequate intraocular pressure control (23), patient decision unrelated to study medication (11), lost to follow-up (16), and noncompliance (9). Adverse events were nonserious and resolved without sequelae. There were no clinically relevant changes in safety parameters. Brinzolamide produced less ocular discomfort (burning/stinging) than timolol, and total carbonic anhydrase inhibition levels remained below that known to cause systemic side effects.

CONCLUSION: Brinzolamide produced significant and equivalent reductions in intraocular pressure when dosed two and three times daily for 18 months. Brinzolamide was safe and well tolerated by patients, with minimal ocular discomfort.

Section snippets

Methods

The study was a multicenter, double-masked, primary therapy trial designed to evaluate the safety and efficacy of brinzolamide 1.0% ophthalmic suspension two and three times daily. Timolol 0.5% (Timoptic, Merck and Company, Inc) ophthalmic solution twice daily was included as a therapeutic reference standard. The primary efficacy parameter was intraocular pressure reduction from baseline. Safety was assessed through the evaluation of adverse events, visual acuity, biomicroscopic examinations,

Results

at 18 investigational sites, 378 patients were randomized to treatment and were included in the safety and intent-to-treat analysis. There were no significant differences between treatment groups with respect to demographics (P > .595; Table 1). The primary efficacy group included 369 patients whose visits were determined to be invaluable for efficacy. One hundred forty-four patients were discontinued from the study after randomization with the most common reasons being the occurrence of an

Discussion

Topical ocular dosing two or three times daily with brinzolamide 1.0% ophthalmic suspension produced clinically relevant and statistically significant intraocular pressure changes from baseline in patients with primary open-angle glaucoma or ocular hypertension. The intraocular pressure reductions were maintained for the 18-month treatment period. The clinical and statistical equivalence of two and three times daily dosing with brinzolamide was demonstrated at all study visits. These findings

Acknowledgements

Statistical consultation was provided by Mark VonTress, PhD, and Russell Andrew, MS, Alcon Laboratories, Inc, Ft Worth, Texas.

THE BRINZOLAMIDE LONG-TERM THERAPY STUDY GROUP INVESTIGATORS

Delmar R. Caldwell, MD, Tulane University, New Orleans, Louisiana; John S. Cohen, MD, Cincinnati Eye Institute, Cincinnati, Ohio; George A. Cioffi, MD, Devers Eye Institute, Portland, Oregon; Miles A. Galin, MD, East Side Ophthalmology, New York, New York; Stephen C. Foster, MD, Boston, Massachusetts; Michael S.

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This research was supported by an unrestricted grant from Research to Prevent Blindness, New York, New York. The study was funded by Alcon Laboratories, Inc, Ft Worth, Texas.

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