An eight-week, multicentric, randomized, interventional, open-label, phase 4, parallel comparison of the efficacy and tolerability of the fixed combination of timolol maleate 0.5%/brimonidine tartrate 0.2% versus fixed combination of timolol maleate 0.5%/dorzolamide 2% in patients with elevated intraocular pressure.

Objective: To compare the efficacy and tolerability of the fixed combination of timolol maleate 0.5%/brimonidine tartrate 0.2% versus fixed combination of timolol maleate 0.5%/dorzolamide 2% in patients with elevated intraocular pressure (IOP) over 8 weeks.

Methods: This 8-week, multicentric, interventional, randomized, open-label, parallel group study was conducted at 4 centers in Brazil and 1 center in Argentina. Patients with open-angle glaucoma or ocular hypertension were randomized to receive bilaterally fixed combination of brimonidine/timolol maleate 0.5% or fixed combination of dorzolamide 2%/timolol 0.5% twice daily at 8:00 AM and 8:00 PM. A modified diurnal tension curve (8:00 AM, 10:30 AM, 02:00 PM, and 4:00 PM) followed by the water drinking test (WDT), which estimates IOP peak of diurnal tension curve, were performed in the baseline and week-8 visits. Adverse events data were recorded at each visit.

Results: A total of 210 patients were randomized (brimonidine/timolol, n=111; dorzolamide/timolol, n=99). Mean baseline IOP was 23.43+/-3.22 mm Hg and 23.43+/-4.06 mm Hg in the patients treated with brimonidine/timolol and dorzolamide/timolol, respectively (P=0.993). Mean diurnal IOP reduction after 8 weeks were 7.02+/-3.06 mm Hg and 6.91+/-3.67 mm Hg, respectively (P=0.811). The adjusted difference between groups (analysis of covariance) at week 8 was not statistically significant (P=0.847). Mean baseline WDT peak was 27.79+/-4.29 mm Hg in the brimonidine/timolol group and 27.68+/-5.46 mm Hg in the dorzolamide/timolol group. After 8 weeks of treatment, mean WDT peaks were 20.94+/-3.76 mm Hg (P<0.001) and 20.98+/-4.19 (P<0.001), respectively. The adjusted difference between groups (analysis of covariance) was not statistically significant (P=0.469). No statistical difference in terms of adverse events was found between groups.

Conclusions: Both fixed combinations were capable of significantly reducing the mean diurnal IOP, mean diurnal peak, and mean WDT peak after 8 weeks of treatment. Also, both fixed combinations are well tolerated with few side effects.