BACKGROUND

Approximately 40% of patients with glaucoma are concomitantly prescribed >or=2 different intraocular pressure (IOP)-lowering medications. An effective and well-tolerated fixed combination of agents requiring once-daily instillation may improve patient compliance.

OBJECTIVE

The purpose of this study was to compare the efficacy and safety profile of the fixed combination latanoprost 0.005% + timolol maleate 0.5% QD with those of latanoprost 0.005% monotherapy QD in patients whose elevated IOP (>or=21 mm Hg) was inadequately controlled by latanoprost.

METHODS

This 21-day, randomized, double-masked, active-control study was conducted at 49 study sites in Argentina, Brazil, Colombia, Mexico, Peru, the United States, and Venezuela. Adults with glaucoma or ocular hypertension who had failed to reach an IOP of <21 mm Hg while receiving latanoprost for at least 28 days were enrolled. After an additional 28 days of latanoprost run-in, patients were randomly assigned to continue latanoprost monotherapy or to switch to the fixed combination for 21 days. The intent-to-treat (ITT) population included all patients who received at least 1 dose of double-masked study medication; the per-protocol (PP) analysis included patients who completed the study without a major protocol violation and who had IOP measurements both at baseline and at day 21. The primary end point was the proportion of patients whose IOP was decreased >or=2 mm Hg from the baseline level on day 21. Proportions of patients demonstrating IOP decreases >or=3, >or=4, or >or=5 mm Hg from the baseline level and of patients reaching an 10P <or=18 mm Hg were evaluated. Adverse events (AEs) were also assessed.

RESULTS

A total of 350 patients were enrolled. In all, 348 patients were included in the ITT and tolerability analyses (fixed combination, n = 175; latanoprost, n = 173; mean [SD] age, 64.4 [13.2] and 63.2 [14.0] years, respectively; 103 women in each group). Baseline demographic and clinical characteristics were similar between groups. A higher percentage of patients receiving the fixed combination had IOP decreases of 2 mm Hg on day 21 relative to baseline compared with latanoprost-treated patients (79.4% vs 51.4%, respectively; P < 0.001). PP analyses found that more patients in the fixed-combination group had IOP decreases >or=3, >or=4, or >or=5 mm Hg (for each target level, P < 0.001 vs latanoprost group) or final IOP 18 mm Hg (fixed -combination, 35.1%; latanoprost, 17.8%; P < 0.001). Both treatments were well tolerated. Similar proportions of patients in the fixed-combination and latanoprost groups reported at least 1 treatment-emergent AE (10.9% and 12.1%, respectively).

CONCLUSION

In this selected population of patients with an inadequate initial IOP response to latanoprost, switching to fixed-combination latanoprosttimolol resulted in a greater decrease in IOP and similar tolerability compared with continuing latanoprost therapy.