Safety and efficacy of bimatoprost/timolol fixed combination in Chinese patients with open-angle glaucoma or ocular hypertension

摘要

Background Lowering intraocular pressure (lOP) is currently the only therapeutic approach in primary open-angle glaucoma.and the fixed-combination medications are needed to achieve sufficiently low target lOP.A multicenter prospective study in the Chinese population was needed to confirm the safety and efficacy of Bimatoprost/Timolol Fixed Combination Eye Drop in China.In this study,we evaluated the safety and efficacy of Bimatoprost/Timolol Fixed Combination with concurrent administration of its components in Chinese patients with open-angle glaucoma or ocular hypertension.Methods In this multicenter,randomized,double-masked,parallel controlled study,patients with open-angle glaucoma or ocular hypertension who were insufficiently responsive to monotherapy with either topical β-blockers or prostaglandin analogues were randomized to one of two active treatment groups in a 1:1 ratio at 11 Chinese ophthalmic departments.Bimatoprost/timolol fixed combination treatment was a fixed combination of 0.03％ bimatoprost and 0.5％ timolol (followed by vehicle for masking) once daily at 19:00 P.M.and concurrent treatment was 0.03％ bimatoprost followed by 0.5％ timolol once daily at 19:00 P.M.The primary efficacy variable was change from baseline in mean diurnal intraocular pressure (IOP) at week 4 visit in the intent-to-treat (ITr) population.Primary analysis evaluated the non-inferiority of bimatoprost/timolol fixed combination to concurrent with respect to the primary variable using a confidence interval (CI) approach.Bimatoprost/timolol fixed combination was to be considered non-inferior to concurrent if the upper limit of the 95％ CI for the between-treatment (bimatoprost/timolol fixed combination minus concurrent) difference was-≤1.5 mmHg.Adverse events were collected and slit-lamp examinations were performed to assess safety.Between-group comparisons of the incidence of adverse events were performed using the Pearson chi-square test or Fisher's exact test.Results Of the enrolled 235 patients,121 patients were randomized to receive bimatoprost/timolol fixed combination and,114 patients were randomized to receive concurrent treatment.At baseline the mean value of mean diurnal IOP was (25.20±3.06) mmHg in the bimatoprost/timolol fixed combination group and (24.87±3.88) mmHg in the concurrent group.The difference between the treatment groups was not statistically significant.The mean change from baseline in mean diurnal IOP (±standard deviation) in the bimatoprost/timolol fixed combination group was (-9.38±4.66) mmHg and it was (-8.93±4.25) mmHg in the concurrent group (P ＜0.01).The difference between the two treatment groups (bimatoprost/timolol fixed combination minus concurrent) in the change from baseline of mean diurnal IOP was-0.556 mmHg (95％ CI:-1.68,0.57,P=0.330).The upper limit of the 95％ CI was less than 1.5 mmHg,the predefined margin of non-inferiority.Adverse events occurred in 26.4％ (32/121)of the bimatoprost/timolol fixed combination patients and 30.7％ (35/114) of the concurrent patients.The most frequent adverse event was conjunctival hyperemia,which was reported as treatment related in 16.5％ (20/121) in the bimatoprost/timolol fixed combination group and 18.4％(21/114) in the concurrent group (P ＞0.05).Conclusions Bimatoprost/Timolol Fixed Combination administered in Chinese patients with open-angle glaucoma or ocular hypertension was not inferior to concurrent dosing with the individual components.Safety profiles were similar between the treatment groups.