THE EFFICACY AND SAFETY OF THE DORZOLAMIDE-TIMOLOL COMBINATION VERSUSTHE CONCOMITANT ADMINISTRATION OF ITS COMPONENTS

Objective: To evaluate whether a fixed combination of 2% dorzolamide a nd 0.5% timolol given twice daily showed equivalent efficacy to the co ncomitant administration of 2% dorzolamide given three times daily and 0.5% timolol given twice daily in patients whose intraocular pressure (IOP) remained elevated during monotherapy with 0.5% timolol twice da ily. Design: Multicenter, parallel, randomized, double-masked clinical trial with an open-label extension. Participants and intervention: In the masked phase, 242 patients received either the dorzolamide-timolo l combination twice daily and placebo three times daily or dorzolamide three times daily and timolol twice daily for up to 3 months, In the open-label extension, 220 patients received the dorzolamide-timolol co mbination twice daily for up to 9 months. Main Outcome Measures: The c riterion for establishing treatment equivalency was a 95% or greater c onfidence that the absolute difference in the mean change in IOP from baseline was less than 1.5 mmHg between treatments, Results: During 3 months of treatment, the dorzolamide-timolol combination reduced IOP r elative to the 0.5% timolol baseline by approximately 14% at hour 0 (j ust before the morning dose), 20% at hour 2, and 15% at hour 8, The IO P-lowering effect of concomitant therapy with dorzolamide and timolol was approximately 16% at hour 0, 20% at hour 2, and 17% at hour 8, At hours 0, 2, and 8, there was greater than 97% confidence that the trea tments were equivalent. During the open-label extension, the mean IOP reduction ranged from 14% to 15% at hour 0 and from 20% to 21% at hour 2. The treatment groups were generally comparable in terms of adverse events, symptoms, ocular signs, visual acuity, visual fields, physica l examination, and laboratory measures. Conclusions: The IOP-lowering effect of the dolzolamide-timolol combination is comparable to that of dorzolamide three times daily plus timolol twice daily and is maintai ned for up to 1 year. The dorzolamide-timolol combination provides cli nically important reduction in IOP relative to baseline treatment with timolol alone and is generally well-tolerated for up to 1 year.