Efficacy and tolerability of timolol maleate ophthalmic gel-forming solution versus timolol ophthalmic solution in adults with open-angle glaucoma orocular hypertension: A six-month, double-masked, multicenter study

Background: Timolol has been formulated in a highly purified gellan gum to improve its duration of action. The efficacy of this formulation in short-t erm studies using once-daily dosing has been reported. Objective: The purpose of this study was to evaluate the efficacy and toler ability of 0.5% timolol maleate ophthalmic gel-forming solution (timolol GS ) given once daily versus 0.5% timolol solution given twice daily in a long -term trial. Methods: This was a multicenter, double-masked, 6-month trial. After a wash out of ocular hypotensive medication. 286 patients with open-angle glaucoma or ocular hypertension were randomly assigned in a 2. 1 ratio to receive 0 .5% timolol GS in both eyes once daily or 0.5% timolol solution in both eye s twice daily. All patients received a morning (9 AM) and evening (9 PM) do se. For patients in the timolol GS group, the evening dose consisted of a v ehicle only, whereas for patients in the timolol solution group, both doses consisted of active drug. Intraocular pressure (IOP) was measured at troug h (before morning instillation) and peak (2 hours after instillation) at fo llow-up examinations at weeks 2, 4, 8, 12, and 24. Adverse events were moni tored using patient reports. Results: Of the 286 patients randomized, 191 received timolol GS and 95 rec eived timolol solution. Ninety-three percent of patients (265/286) complete d the study. At the end of the treatment interval (week 24), the mean decre ase in IOP at trough ranged from 5.6 to 5.9 mm Hg in the timolol GS group a nd from 6.3 to 6.6 mm Hg in the timolol solution group. Similar efficacy wa s observed at 11 AM (peak). At week 24, the difference in mean IOP between treatments was -0.61 mm Hg (95% CI -1.44 to 0.22) at trough and -0.79 mm Hg (95% CI -1.77 to 0.20) at peak, indicating no significant difference betwe en the 2 timolol formulations. The number of reports of blurred vision and tearing was significantly higher in the timolol GS group than in the timolo l solution group (P = 0.04), whereas burning/stinging was reported more fre quently in the timolol solution group than in the timolol GS group (P = 0.0 4). At week 12, the decrease in mean heart rate at trough (hour 0) was sign ificantly less for patients in the timolol GS group than for those in the t imolol solution group (-1.1 vs -4.2 bpm; P = 0.024). At week 24 (hour 0), t he decrease in mean heart rate was less for patients treated with timolol G S by 2.5 bpm (P = 0.051). The heart rate data at peak (hour 2) was similar to that observed at trough at week 12 (-2.7 vs -5.7 bpm; P = 0.006) and wee k 24 (-3.1 vs -4.7 bpm; P = 0.063). The mean change in blood pressure was n ot significantly different between treatments. There were no clinically sig nificant differences between the groups in visual acuity. biomicroscopy and ophthalmoscopy results, or visual fields. Conclusions: Timolol 0.5% GS administered once daily was shown to be as eff ective in lowering IOP as the equivalent concentration of timolol 0.5% solu tion administered twice daily in patients with ocular hypertension or open- angle glaucoma.