Dorzolamide/timolol combination versus concomitant administration of brimonidine and timolol: six-month comparison of efficacy and tolerability.
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.
Sall
Kenneth N
KN
Sall Eye Surgery Medical Center Inc., Bellflower, California, USA.
Greff
Linda J
LJ
Johnson-Pratt
Lisa R
LR
DeLucca
Paul T
PT
Polis
Adam B
AB
Kolodny
Andrea H
AH
Fletcher
Charlena A
CA
Cassel
Deborah A
DA
Boyle
Denise R
DR
Skobieranda
Franck
F
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
D000959:Antihypertensive Agents; D009883:Ophthalmic Solutions; D011810:Quinoxalines; D013449:Sulfonamides; D013876:Thiophenes; D000068438:Brimonidine Tartrate; D013999:Timolol; C062765:dorzolamide