title: Dorzolamide/timolol combination versus concomitant administration of brimonidine and timolol: six-month comparison of efficacy and tolerability.
abstract: OBJECTIVE
  To compare the efficacy and tolerability of the 2% dorzolamide/0.5% timolol combination ophthalmic solution twice daily to the concomitant administration of 0.2% brimonidine ophthalmic solution twice daily and 0.5% timolol ophthalmic solution twice daily.
  
  
  METHODS
  Randomized, multicenter, observer-masked, parallel-group study.
  
  
  METHODS
  Two hundred ninety-three patients with ocular hypertension or primary open-angle glaucoma participated.
  
  
  METHODS
  After an open-label 3-week 0.5% timolol run-in period, patients with an hour 2 intraocular pressure (IOP) of > or = 22 mmHg were randomly assigned to receive either the dorzolamide/timolol combination twice daily or the concomitant use of brimonidine twice daily and timolol twice daily (brimonidine + timolol) for 6 months.
  
  
  METHODS
  The IOP-lowering effects at hour 0 and hour 2 were collected at 1, 3, and 6 months. We hypothesized that both treatment regimens would have comparable hour 2 IOP-lowering effects at month 3. The treatments were considered comparable if the two-sided 95% confidence interval of the treatment difference was within +/- 1.5 mmHg. Tolerability data were also collected at 1, 3, and 6 months.
  
  
  RESULTS
  The primary efficacy analysis was based on the modified intent-to-treat population. At month 3, hour 2, the dorzolamide/timolol group had an adjusted mean (standard error) change in IOP of -5.04 (0.30) mmHg versus -5.41 (0.30) mmHg in the brimonidine + timolol group, with a treatment difference of 0.36 (0.40) mmHg (95% confidence interval [CI] of -0.42-1.14 mmHg). At month 3, hour 0, the dorzolamide/timolol group had a change in IOP of -3.66 (0.29) mmHg versus -4.15 (0.28) mmHg in the brimonidine + timolol group, with a treatment difference of 0.49 (0.39) mmHg (95% CI of -0.27-1.25 mmHg). Likewise, at all other observed time points, the 95% confidence interval of the treatment difference was within +/- 1.5 mmHg. Ninety-three patients (64%) in the dorzolamide/timolol group and 88 patients (60%) in the brimonidine + timolol group had adverse experiences that were deemed drug related by the investigator, for which 7 patients (5%) in the dorzolamide/timolol group and 8 patients (5%) in the brimonidine + timolol group were discontinued from the study.
  
  
  CONCLUSIONS
  The efficacy of the dorzolamide/timolol combination and the concomitant administration of brimonidine and timolol were comparable. The incidence of drug-related adverse experiences and the incidence of discontinuations caused by drug-related adverse experiences were similar between groups.
authors.affiliation: Sall Eye Surgery Medical Center Inc., Bellflower, California, USA.
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Sall
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Greff
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Johnson-Pratt
authors.forename: Paul T
authors.initials: PT
authors.lastname: DeLucca
authors.forename: Adam B
authors.initials: AB
authors.lastname: Polis
authors.forename: Andrea H
authors.initials: AH
authors.lastname: Kolodny
authors.forename: Charlena A
authors.initials: CA
authors.lastname: Fletcher
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Cassel
authors.forename: Denise R
authors.initials: DR
authors.lastname: Boyle
authors.forename: Franck
authors.initials: F
authors.lastname: Skobieranda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068438:Brimonidine Tartrate; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy / Q000503:physiopathology; D009883:Ophthalmic Solutions; D011446:Prospective Studies; D011810:Quinoxalines / Q000009:adverse effects / Q000627:therapeutic use*; D012449:Safety; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D013999:Timolol / Q000009:adverse effects / Q000627:therapeutic use*; D014792:Visual Acuity; D014794:Visual Fields
chemical_list: D000959:Antihypertensive Agents; D009883:Ophthalmic Solutions; D011810:Quinoxalines; D013449:Sulfonamides; D013876:Thiophenes; D000068438:Brimonidine Tartrate; D013999:Timolol; C062765:dorzolamide