Objective: To evaluate the efficacy and safety of fixed-combination brimonidine tartrate 0.2%/timolol 0.5% ophthalmic solution dosed BID and demonstrate non-inferiority to concomitant use of brimonidine tartrate 0.2% BID and timolol 0.5% BID in glaucoma and ocular hypertension patients with intraocular pressure (IOP) uncontrolled on monotherapy.

Methods: Randomized, multicenter, double-masked, parallel-group study involving 371 patients with inadequate IOP control (IOP from 22 to 34 mmHg) after >=3 weeks of run-in on any monotherapy. Patients were treated with fixed-combination brimonidine/timolol BID (fixed-combination group, n=188) or concomitant brimonidine BID and timolol BID (concomitant group, n=183). IOP was assessed pre-dose and 2 hours after morning dosing at weeks 2, 6, and 12.

Results: A total of 355 patients (96%) completed the study. Patient demographics, run-in monotherapy, and baseline mean IOP on monotherapy were comparable between treatment groups. During follow-up, the mean reduction from baseline IOP was significant (p<0.001) at all time points and ranged from 4.4 to 5.3 mmHg in each group. Brimonidine/timolol fixed combination was as effective as concomitant therapy with respect to mean IOP and mean change from baseline IOP at all time points and visits. Between-group differences were <=0.35 mmHg for mean IOP and <=0.30 mmHg for mean change from baseline IOP; none were significant. No unexpected side effects were associated with the fixed combination. Both treatments were well tolerated with no difference in adverse events between groups.

Conclusions: Brimonidine/timolol fixed-combination therapy is as safe and effective as concomitant treatment with the individual components. Its simplified dosing regimen has the potential to improve compliance. (Eur J Ophthalmol 2005; 15: 581-90).