PURPOSE: To evaluate the effects of a bimatoprost/timolol fixed combination (BTFC) and a latanoprost/timolol fixed combination (LTFC) on diurnal intraocular pressure (IOP) and anterior ocular parameters in healthy subjects. METHODS: We enrolled 58 healthy subjects in this prospective clinical study. Thirty subjects were treated with BTFC and 28 subjects were treated with LTFC. IOP was measured every 2 hours except from 01:00 and 05:00. Axial length, corneal curvature, and anterior chamber depth were obtained using the IOL master at baseline and 24 hours later. Adverse events were assessed by patient interview and by slit lamp examination. RESULTS: The largest difference in IOP between treated and untreated eyes 8 hours after instillation was 1.67 mmHg in the BTFC group (p < 0.001). The largest difference in IOP between treated and untreated eyes 10 hours after instillation was 1.93 mmHg in the LTFC group (p < 0.001). For anterior ocular parameters such as axial length, corneal curvature, anterior chamber depth at baseline and 24 hours after instillation, there were no significant differences between the baseline and 24-hour values in either the BTFC or LTFC group. The most frequently occurring adverse event was conjunctival hyperemia, which was found in 33.3% (n = 10) of the BTFC group and 25.0% (n = 7) of the LTFC group (p = 0.486). CONCLUSIONS: BTFC and LTFC provided a significant reduction in IOP from baseline without changing any anterior ocular parameters. Our results provide a reference for monocular trials to assess the effect of eye drops in a clinical condition.
Adult ; Aged ; Aged, 80 and over ; Amides/*administration & dosage ; Antihypertensive Agents/administration & dosage ; Circadian Rhythm/*physiology ; Cloprostenol/administration & dosage/*analogs & derivatives ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Glaucoma, Open-Angle/drug therapy/*physiopathology ; Healthy Volunteers ; Humans ; Intraocular Pressure/drug effects/*physiology ; Male ; Middle Aged ; Ophthalmic Solutions ; Prospective Studies ; Prostaglandins F, Synthetic/*administration & dosage ; Timolol/*administration & dosage ; Tonometry, Ocular ; Treatment Outcome

PURPOSE: To evaluate the effects of a bimatoprost/timolol fixed combination (BTFC) and a latanoprost/timolol fixed combination (LTFC) on diurnal intraocular pressure (IOP) and anterior ocular parameters in healthy subjects. METHODS: We enrolled 58 healthy subjects in this prospective clinical study. Thirty subjects were treated with BTFC and 28 subjects were treated with LTFC. IOP was measured every 2 hours except from 01:00 and 05:00. Axial length, corneal curvature, and anterior chamber depth were obtained using the IOL master at baseline and 24 hours later. Adverse events were assessed by patient interview and by slit lamp examination. RESULTS: The largest difference in IOP between treated and untreated eyes 8 hours after instillation was 1.67 mmHg in the BTFC group (p < 0.001). The largest difference in IOP between treated and untreated eyes 10 hours after instillation was 1.93 mmHg in the LTFC group (p < 0.001). For anterior ocular parameters such as axial length, corneal curvature, anterior chamber depth at baseline and 24 hours after instillation, there were no significant differences between the baseline and 24-hour values in either the BTFC or LTFC group. The most frequently occurring adverse event was conjunctival hyperemia, which was found in 33.3% (n = 10) of the BTFC group and 25.0% (n = 7) of the LTFC group (p = 0.486). CONCLUSIONS: BTFC and LTFC provided a significant reduction in IOP from baseline without changing any anterior ocular parameters. Our results provide a reference for monocular trials to assess the effect of eye drops in a clinical condition.
Adult ; Aged ; Aged, 80 and over ; Amides/*administration & dosage ; Antihypertensive Agents/administration & dosage ; Circadian Rhythm/*physiology ; Cloprostenol/administration & dosage/*analogs & derivatives ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Glaucoma, Open-Angle/drug therapy/*physiopathology ; Healthy Volunteers ; Humans ; Intraocular Pressure/drug effects/*physiology ; Male ; Middle Aged ; Ophthalmic Solutions ; Prospective Studies ; Prostaglandins F, Synthetic/*administration & dosage ; Timolol/*administration & dosage ; Tonometry, Ocular ; Treatment Outcome

BACKGROUNDLowering intraocular pressure (IOP) is currently the only therapeutic approach in primary open-angle glaucoma. and the fixed-combination medications are needed to achieve sufficiently low target IOP. 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.

METHODSIn 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 (ITT) 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.

RESULTSOf 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).

CONCLUSIONSBimatoprost/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.

Adolescent ; Adult ; Aged ; Amides ; administration & dosage ; adverse effects ; therapeutic use ; Bimatoprost ; Cloprostenol ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Female ; Glaucoma, Open-Angle ; drug therapy ; Humans ; Male ; Middle Aged ; Ocular Hypertension ; drug therapy ; Timolol ; administration & dosage ; adverse effects ; therapeutic use ; Young Adult