Twelve-week, randomized, multicenter study comparing a fixed combination of brimonidine-timolol with timolol as therapy adjunctive to latanoprost

Abstract

Objective

To evaluate the additive intraocular pressure (IOP)-lowering efficacy and safety of fixed-combination brimonidine 0.2%/timolol 0.5% compared with timolol 0.5% at peak and trough effect when used as therapy adjunctive to latanoprost 0.005% in patients with glaucoma or ocular hypertension who require additional IOP lowering.

Methods

In this prospective, randomized, multicenter, investigator-masked, parallel-group study, patients were treated with latanoprost monotherapy for at least four weeks prior to baseline. At baseline on latanoprost, patients with IOP ≥21 mmHg in at least one eye were randomized to twice-daily fixed brimonidine-timolol (n = 102) or timolol (n = 102), each adjunctive to latanoprost for 12 weeks. IOP was measured at 8 am and 10 am at baseline, week 6, and week 12 and evaluated in the per protocol population. The primary efficacy endpoint was peak IOP lowering at 10 am, week 12. Safety measures included adverse events.

Results

Baseline mean IOP was similar at 10 am in the treatment groups (brimonidine-timolol 23.4 mmHg; timolol 23.0 mmHg). The mean additional reduction from latanoprost-treated baseline IOP was 8.3 mmHg (35.5%) with fixed brimonidine-timolol and 6.2 mmHg (27.0%) with timolol at 10 am, week 12 (P < 0.001). Patients treated with fixed brimonidine-timolol adjunctive to latanoprost were significantly more likely than patients treated with adjunctive timolol to achieve an IOP <18 mmHg (P = 0.028) and a ≥20% reduction in IOP from baseline (P = 0.047) at both 8 am and 10 am in week 12. Adverse events occurred in 14.7% of fixed brimonidine-timolol patients and 12.7% of timolol patients. Biomicroscopy findings were similar between the treatment groups after 12 weeks of treatment.

Conclusion

Fixed-combination brimonidine-timolol reduced IOP significantly more effectively than timolol when used as adjunctive therapy to latanoprost in patients with glaucoma and ocular hypertension. Both fixed brimonidine-timolol and timolol were well tolerated as agents adjunctive to latanoprost.

Keywords:

• brimonidine
• drug combinations
• glaucoma
• intraocular pressure
• ocular hypertension
• timolol

Acknowledgments

Renaissance Associates (Newport Beach, CA), a clinical research organization, was retained by Allergan to manage the study. Renaissance Associates personnel monitored the study sites and performed all data entry and analysis. RDF was supported, in part, by an unrestricted grant from Research to Prevent Blindness. Kate Ivins provided medical writing assistance in the development of the manuscript. Principal investigators in this study were Ike Ahmed (Toronto, ON, Canada), Louis Alpern (El Paso, TX), Edward Chang (Pittsburgh, PA), Anastasios Costarides (Atlanta, GA), Douglas Day (Atlanta, GA), Robert Fechtner (Newark, NJ), Brian Flowers (Fort Worth, TX), Paul Harasymowycz (Montreal, QC, Canada), Barry Katzman, (San Diego, CA), Norman Levy (Gainesville, FL), Donald Nixon (Orillia, ON, Canada), William Rand (Pompano Beach, FL), Steven Vold (Rogers, AK), Mark Weiss (Tulsa, OK), and Fiaz Zaman (Houston, TX).

Disclosure

This study was sponsored by Allergan Inc. RDF is a consultant to and has received research support from Allergan Inc. PH, DRN, SDV, and FZ have also received research support from Allergan Inc. JW and DAH are employees of Allergan Inc.