A 12 Week Study Comparing the Fixed Combination of Latanoprost and Timolol with the Concomitant Use of the Individual Components in Patients with Open Angle Glaucoma and Ocular Hypertension

Background: To compare the intraocular pressure (IOP) lowering effect and safety of the fixed combination of latanoprost and timolol with that of the concomitant use of the individual components.

Methods: A 12 week, double masked, randomised, crossover, multicentre study of patients with open angle glaucoma or ocular hypertension and IOP controlled on ocular hypotensive treatment (mean < or =21 mmHg). Patients received either a once daily morning dose of the fixed combination of latanoprost 0.005% and timolol 0.5% or once daily evening latanoprost 0.005% and twice daily timolol 0.5% for six weeks and then switched to the other combination. The primary efficacy endpoint was the within-patient difference in diurnal IOP between fixed and unfixed treatment combinations after six weeks of treatment; a one sided 97.5% confidence interval (CI) for the mean difference in IOP <1.0 mmHg indicated the fixed combination was not inferior to the unfixed combination. Adverse events were recorded at each visit.

Results: In all, 190 patients were included in observed cases analyses (93 fixed to unfixed combination; 97 unfixed to fixed combination). Mean IOP at baseline was 16.9 mmHg in both groups. The mean diurnal IOP was 17.0 mmHg after fixed combination treatment and 15.9 mmHg after unfixed combination therapy (p<0.0001). The difference in mean within-patient diurnal IOP was 1.1 mmHg favouring the unfixed combination (95% CI 0.8 to 1.4 mmHg). Both treatments were tolerated well.

Conclusions: Although the primary efficacy endpoint was not met, once daily administration of the fixed combination of latanoprost and timolol was found to be safe and effective. The fixed combination provides a convenient alternative to the three instillations required with the individual components.