A RANDOMIZED TRIAL COMPARING THE DORZOLAMIDE-TIMOLAL COMBINATION GIVEN TWICE-DAILY TO MONOTHERAPY WITH TIMOLOL AND DORZOLAMIDE

Objective: To compare the efficacy and safety of a fixed combination o f 2.0% dorzolamide and 0.5% timolol administered twice daily with each of the individual components administered in their usual monotherapy dose regimens in patients who had washed out all ocular hypotensive me dications. Design: A 3-month, parallel, randomized, double-masked, act ive-controlled, multicenter clinical trial. Participants: A total of 3 35 patients with bilateral ocular hypertension or open-angle glaucoma participated. Intervention: After completing a washout of ocular hypot ensive medications, patients were randomized to receive either the dor zolamide-timolol combination twice daily plus placebo once daily, 0.5% timolol twice daily plus placebo once daily, or 2.0% dorzolamide thre e times daily. Main Outcome Measures: Intraocular pressure (IOP) was m easured at morning trough (hour 0) and peak (2 hours postdose) on day 1, week 2, and months 1, 2, and 3, Ocular and systemic safety were eva luated at each study visit. Results: Intraocular pressure reduction wa s greater on average in the combination group than in the dorzolamide and timolol groups. At morning trough (month 3, hour 0), the mean redu ction in IOP from baseline was 27.4% (-7.7 mmHg) for the combination, 15.5% (-4.6 mmHg) for dorzolamide, and 22.2% (-6.4 mmHg) for timolol, At morning peak (month 3, hour 2), the mean IOP reduction from baselin e was 32.7% (-9.0 mmHg), 19.8% (-5.4 mmHg), and 22.6% (-6.3 mmHg) for the combination, dorzolamide, and timolol, respectively. Overall, the incidence of clinical adverse experiences was comparable between the c ombination and each of its components. The proportion of patients who discontinued from the study because of clinical adverse experiences wa s also comparable between the combination and dorzolamide, although it was significantly greater in the combination group than in the timolo l group (7% vs. 1%, P = 0.035), Similarly, comparable numbers of patie nts in the combination and dorzolamide groups reported ocular symptoms ; however, when compared to the timolol group, more patients receiving the combination reported blurred vision, burning eye, stinging eye, a nd tearing eye. Conclusions: After a washout of ocular hypotensive the rapy the IOP-lowering effect of the dorzolamide-timolol combination wa s greater than that of either of its components administered as monoth erapy, The combination is generally well-tolerated and provides a conv enient alternative to concomitant therapy with its individual componen ts.