Comparative efficacy and safety of the fixed versus unfixed combination of latanoprost and timolol in Chinese patients with open-angle glaucoma or ocular hypertension

Background: A noninferiority trial was conducted to evaluate the efficacy of a single evening dose of fixed-combination latanoprost 50 mu g/mL and timolol 0.5 mg/mL (Xalacom (R); LTFC), in Chinese patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH) who were insufficiently controlled on beta-blocker monotherapy or beta-blocker-based dual therapy. Methods: This 8-week, randomized, open-label, parallel-group, noninferiority study compared once-daily evening dosing of LTFC with the unfixed combination of latanoprost, one drop in the evening, and timolol, one drop in the morning (LTuFC). The primary efficacy endpoint was the mean change from baseline to week 8 in diurnal intraocular pressure (IOP; mean of 8 AM, 10 AM, 2 PM, 4 PM IOPs). LTFC was considered noninferior to LTuFC if the upper limit of the 95% confidence interval (CI) of the difference was < 1.5 mmHg (analysis of covariance). Results: Baseline characteristics were similar for LTFC (N = 125; POAG, 70%; mean IOP, 25.8 mmHg) and LTuFC (N = 125; POAG, 69%; mean IOP, 26.0 mmHg). Mean diurnal IOP changes from baseline to week 8 were -8.6 mmHg with LTFC and -8.9 mmHg with LTuFC (between-treatment difference: -0.3 mmHg; 95%-CI, -0.3 to 1.0). Both treatments were well tolerated. Conclusions: A single evening dose of LTFC was at least as effective as the unfixed combination of latanoprost in the PM and timolol in the AM in reducing IOP in Chinese subjects with POAG or OH whose IOP was insufficiently reduced with b-blocker monotherapy or beta-blocker-based dual therapy. LTFC is an effective and well tolerated once-daily treatment for POAG and OH. Trial registration: Clinicaltrials.gov registration: NCT00219596