title: Safety and efficacy of bimatoprost/timolol fixed combination in Chinese patients with open-angle glaucoma or ocular hypertension.
abstract: BACKGROUND
  Lowering 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.
  
  
  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 (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.
  
  
  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.
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai 200031, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Ling
authors.affiliation: Department of Ophthalmology, Wuhan Union Hospital, Wuhan, Hubei 430022, China.
authors.forename: Mingchang
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Wuhan Union Hospital, Wuhan, Hubei 430022, China.
authors.forename: Yizhen
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Ophthalmology, Southwest Hospital, Chongqing 400038, China.
authors.forename: Zhengqin
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
authors.forename: Yiqiao
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Department of Ophthalmology, Eye Hospital Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
authors.forename: Aiwu
authors.initials: A
authors.lastname: Fang
authors.affiliation: Department of Ophthalmology, Daping Hospital of Third Military Medical University, Chongqing 400042, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Ophthalmology, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.
authors.forename: Dachuan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Xi Jing Hospital of Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Qingdao Ophthalmology Hospital, Qingdao, Shandong 266071, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Henan Ophthalmology Institution, Zhengzhou, Henan 450003, China.
authors.forename: Yangceng
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital, Fudan University, Shanghai 200031, China. Email: xhsun@shmu.edu.cn.
authors.forename: Xinghuai
authors.initials: X
authors.lastname: Sun
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000577:Amides / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D000069580:Bimatoprost; D003008:Cloprostenol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy*; D013999:Timolol / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000577:Amides; D003008:Cloprostenol; D013999:Timolol; D000069580:Bimatoprost