title: Three-month randomized trial of fixed-combination brinzolamide, 1%, and brimonidine, 0.2%.
abstract: OBJECTIVE
  This study evaluates the contribution of the individual components of an investigational non-β-antagonist fixed combination of brinzolamide, 1%, and brimonidine, 0.2%. This study and its sister study provide the first randomized data showing the intraocular pressure (IOP)-lowering activity and the toxicity profile of this novel topical antihypertensive fixed combination.
  
  
  OBJECTIVE
  To compare IOP-lowering efficacy of fixed-combination brinzolamide, 1%, and brimonidine, 0.2%, with that of its components in patients with open-angle glaucoma or ocular hypertension.
  
  
  METHODS
  In this phase 3, double-masked, parallel-group, multicenter study, eligible patients were randomized 1:1:1 to treatment with fixed-combination brinzolamide, 1%, and brimonidine, 0.2%; brinzolamide, 1%; or brimonidine, 0.2%, 3 times daily for 3 months.
  
  
  METHODS
  Sixty-six academic and private practice study sites throughout the United States.
  
  
  METHODS
  A total of 660 adults with a clinical diagnosis of open-angle glaucoma or ocular hypertension from a referred sample were enrolled. Thirty-four patients discontinued participation due to treatment-related nonserious adverse events.
  
  
  METHODS
  Topical administration of study medication (fixed-combination brinzolamide, 1%, and brimonidine, 0.2%; brinzolamide, 1%; or brimonidine, 0.2%) 1 drop 3 times daily for 3 months.
  
  
  METHODS
  Mean IOP at the 3-month visit at all time points (8 AM, 10 AM, 3 PM, and 5 PM).
  
  
  RESULTS
  A total of 660 patients were enrolled. Baseline mean IOP values were similar among treatment groups at all 4 time points. At 3 months, the mean IOP of the brinzolamide-brimonidine group (16.3-19.8 mm Hg) was significantly lower than that of either the brinzolamide group (19.3-20.9 mm Hg; P ≤ .002) or the brimonidine group (17.9-22.5 mm Hg; P < .001) across all time points. One of 10 serious adverse events (chest pain, brinzolamide group) was judged as treatment related. A total of 129 patients experienced at least 1 treatment-related adverse effect (brinzolamide-brimonidine, 22.9%; brinzolamide, 18.6%; and brimonidine, 17.3%; P = .31), most of which were ocular.
  
  
  CONCLUSIONS
  This registrational study provides evidence that the fixed combination of brinzolamide, 1%, and brimonidine, 0.2%, can safely and effectively lower IOP in patients with open-angle glaucoma or ocular hypertension, showing significantly superior IOP-lowering activity compared with either brinzolamide or brimonidine monotherapy while providing a safety profile consistent with that of its individual components.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01297517.
authors.affiliation: Huron Ophthalmology, Ypsilanti, Michigan 48197, USA. glbjkatz@hotmail.com
authors.forename: Gregory
authors.initials: G
authors.lastname: Katz
authors.forename: Harvey
authors.initials: H
authors.lastname: Dubiner
authors.forename: John
authors.initials: J
authors.lastname: Samples
authors.forename: Steven
authors.initials: S
authors.lastname: Vold
authors.forename: Kenneth
authors.initials: K
authors.lastname: Sall
mesh_terms: D000046:Academic Medical Centers; D060433:Administration, Ophthalmic; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D000068438:Brimonidine Tartrate; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003941:Diagnostic Techniques, Ophthalmological; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D009883:Ophthalmic Solutions; D011237:Predictive Value of Tests; D011331:Private Practice; D011810:Quinoxalines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013843:Thiazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D002257:Carbonic Anhydrase Inhibitors; D004338:Drug Combinations; D009883:Ophthalmic Solutions; D011810:Quinoxalines; D013449:Sulfonamides; D013843:Thiazines; D000068438:Brimonidine Tartrate; C111827:brinzolamide