title: Travoprost 0.004%/timolol 0.5%-fixed combination with and without benzalkonium chloride: a prospective, randomized, doubled-masked comparison of safety and efficacy.
abstract: OBJECTIVE
  The purpose of this study is to compare the safety and intraocular pressure (IOP)-lowering efficacy of travoprost/timolol in a benzalkonium chloride (BAK)-free fixed combination preserved with polyquaternium-1 (TRA/TIM BAK-free), with travoprost/timolol-fixed combination preserved with BAK (TRA/TIM), in patients with open-angle glaucoma or ocular hypertension.
  
  
  METHODS
  In this prospective randomized controlled trial, subjects with IOP of at least 22  mm Hg in one or both eyes at 0900  h, and IOP of at least 21  mm Hg in one or both eyes at 1100  h and 1600  h at two eligibility visits were randomly assigned to receive either TRA/TIM BAK-free (n=195) or TRA/TIM (n=193), dosed once daily in the morning (0900  h) for 6 weeks. IOP was assessed at 0900  h, 1100  h, and 1600  h at each scheduled visit (baseline, 2 and 6 weeks after randomization).
  
  
  RESULTS
  Mean IOP reduction across all visits and time points was 8.0  mm Hg in the TRA/TIM BAK-free group and 8.4  mm Hg in the TRA/TIM group (P=0.0943). The difference in mean IOP between groups ranged from 0.2 to 0.7  mm Hg across visits and time points, with a mean pooled difference of 0.4  mm Hg (95% CI: -0.1 to 0.8), demonstrating equivalence of the two formulations. The most common drug-related adverse event was hyperemia of the eye (ocular hyperemia and conjunctival hyperemia combined), occurring in 11.8% of the TRA/TIM BAK-free group and 13.0% of the TRA/TIM group.
  
  
  CONCLUSIONS
  Travoprost/timolol BAK-free demonstrated equivalence to travoprost/timolol preserved with BAK in efficacy. No clinically relevant differences in the safety profiles of travoprost/timolol BAK-free and travoprost/timolol preserved with BAK were identified.
authors.affiliation: Department of Ophthalmology, Gifu University Graduate School of Medicine, Gifu, Japan. yoshikit-gif@umin.net
authors.forename: Y
authors.initials: Y
authors.lastname: Kitazawa
authors.forename: P
authors.initials: P
authors.lastname: Smith
authors.forename: N
authors.initials: N
authors.lastname: Sasaki
authors.forename: S
authors.initials: S
authors.lastname: Kotake
authors.forename: K
authors.initials: K
authors.lastname: Bae
authors.forename: Y
authors.initials: Y
authors.lastname: Iwamoto
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001548:Benzalkonium Compounds / Q000627:therapeutic use*; D003008:Cloprostenol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D007564:Japan; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy / Q000503:physiopathology; D011108:Polymers / Q000627:therapeutic use; D011446:Prospective Studies; D013999:Timolol / Q000009:adverse effects / Q000627:therapeutic use*; D000069557:Travoprost; D014481:United States
chemical_list: D000959:Antihypertensive Agents; D001548:Benzalkonium Compounds; D011108:Polymers; D003008:Cloprostenol; C058655:polyquaternium 1; D013999:Timolol; D000069557:Travoprost