A 12-week, randomized, double-masked, multicenter study of the fixed combination of latanoprost and timolol in the evening versus the individual components.
OBJECTIVE
To compare the efficacy and tolerability of fixed-combination latanoprost and timolol applied in the evening with the concomitant use of the individual components.


METHODS
Twelve-week, randomized, double-masked, multicenter study.


METHODS
Five hundred seventeen randomized patients with ocular hypertension; open-angle, pigmentary, or exfoliation glaucoma; and baseline (after washout) intraocular pressure (IOP) levels between 23 and 33 mmHg.


METHODS
Patients received either the fixed combination of latanoprost and timolol once daily in the evening and a placebo in the morning and evening or the unfixed combination of latanoprost once daily in the evening and timolol in the morning and evening. Study visits were at weeks 2, 6, and 12.


METHODS
The primary efficacy end point was mean change from baseline to week 12 in diurnal IOP (mean IOPs of 8 am, 12 pm, and 4 pm). The fixed combination was considered noninferior to the unfixed combination if the upper limit of the 95% confidence interval (CI) of the difference was <1.5 mmHg (analysis of covariance). Adverse events were recorded at each visit.


RESULTS
In all, 502 patients were included in intent-to-treat analyses (fixed combination, n = 255; unfixed combination, n = 247). For the fixed- and unfixed-combination groups, mean baseline diurnal IOP levels were 25.4 mmHg and 25.2 mmHg, respectively, and mean diurnal IOP reductions were 8.7 mmHg and 9.0 mmHg (between-treatment difference, 0.3 mmHg; 95% CI, -0.1 to 0.7 mmHg; P = 0.15). Both treatments were well tolerated.


CONCLUSIONS
The fixed combination of latanoprost and timolol administered once daily in the evening is not inferior to the unfixed combination of latanoprost once daily in the evening and timolol twice daily. The fixed combination provides an effective and well-tolerated alternative to multiple instillations.
Diestelhorst
Michael
M
Department of Ophthalmology, Univerisitäts-Augenklinik, University of Cologne, Cologne, Germany. michael.diestelhorst@medizin.uni-koeln.de
Larsson
Lill-Inger
LI
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004338:Drug Combinations; D017889:Exfoliation Syndrome / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D000077338:Latanoprost; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy; D011461:Prostaglandins F, Synthetic / Q000009:adverse effects / Q000627:therapeutic use*; D013999:Timolol / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000959:Antihypertensive Agents; D004338:Drug Combinations; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost; D013999:Timolol