title: The efficacy and safety of the dorzolamide-timolol combination versus the concomitant administration of its components. Dorzolamide-Timolol Study Group.
abstract: OBJECTIVE
  To evaluate whether a fixed combination of 2% dorzolamide and 0.5% timolol given twice daily showed equivalent efficacy to the concomitant administration of 2% dorzolamide given three times daily and 0.5% timolol given twice daily in patients whose intraocular pressure (IOP) remained elevated during monotherapy with 0.5% timolol twice daily.
  
  
  METHODS
  Multicenter, parallel, randomized, double-masked clinical trial with an open-label extension.
  
  
  METHODS
  In the masked phase, 242 patients received either the dorzolamide-timolol combination twice daily and placebo three times daily or dorzolamide three times daily and timolol twice daily for up to 3 months. In the open-label extension, 220 patients received the dorzolamide-timolol combination twice daily for up to 9 months.
  
  
  METHODS
  The criterion for establishing treatment equivalency was a 95% or greater confidence that the absolute difference in the mean change in IOP from baseline was less than 1.5 mmHg between treatments.
  
  
  RESULTS
  During 3 months of treatment, the dorzolamide-timolol combination reduced IOP relative to the 0.5% timolol baseline by approximately 14% at hour 0 (just before the morning dose), 20% at hour 2, and 15% at hour 8. The IOP-lowering effect of concomitant therapy with dorzolamide and timolol was approximately 16% at hour 0.20% at hour 2, and 17% at hour 8. At hours 0, 2, and 8, there was greater than 97% confidence that the treatments were equivalent. During the open-label extension, the mean IOP reduction ranged from 14% to 15% at hour 0 and from 20% to 21% at hour 2. The treatment groups were generally comparable in terms of adverse events, symptoms, ocular signs, visual acuity, visual fields, physical examination, and laboratory measures.
  
  
  CONCLUSIONS
  The IOP-lowering effect of the dorzolamide-timolol combination is comparable to that of dorzolamide three times daily plus timolol twice daily and is maintained for up to 1 year. The dorzolamide-timolol combination provides clinically important reduction in IOP relative to baseline treatment with timolol alone and is generally well-tolerated for up to 1 year.
authors.affiliation: Department of Clinical Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
authors.forename: K
authors.initials: K
authors.lastname: Strohmaier
authors.forename: E
authors.initials: E
authors.lastname: Snyder
authors.forename: H
authors.initials: H
authors.lastname: DuBiner
authors.forename: I
authors.initials: I
authors.lastname: Adamsons
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy*; D009883:Ophthalmic Solutions; D012449:Safety; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013999:Timolol / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000319:Adrenergic beta-Antagonists; D002257:Carbonic Anhydrase Inhibitors; D009883:Ophthalmic Solutions; D013449:Sulfonamides; D013876:Thiophenes; D013999:Timolol; C062765:dorzolamide