Efficacy and tolerability of timolol maleate ophthalmic gel-forming solution versus timolol ophthalmic solution in adults with open-angle glaucoma or ocular 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-term studies using once-daily dosing has been reported.


OBJECTIVE
The purpose of this study was to evaluate the efficacy and tolerability 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 washout 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 eyes twice daily. All patients received a morning (9 AM) and evening (9 PM) dose. For patients in the timolol GS group, the evening dose consisted of a vehicle only, whereas for patients in the timolol solution group, both doses consisted of active drug. Intraocular pressure (IOP) was measured at trough (before morning instillation) and peak (2 hours after instillation) at follow-up examinations at weeks 2, 4, 8, 12, and 24. Adverse events were monitored using patient reports.


RESULTS
Of the 286 patients randomized, 191 received timolol GS and 95 received timolol solution. Ninety-three percent of patients (265/286) completed the study. At the end of the treatment interval (week 24), the mean decrease in IOP at trough ranged from 5.6 to 5.9 mm Hg in the timolol GS group and from 6.3 to 6.6 mm Hg in the timolol solution group. Similar efficacy was 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 between the 2 timolol formulations. The number of reports of blurred vision and tearing was significantly higher in the timolol GS group than in the timolol solution group (P = 0.04), whereas burning/stinging was reported more frequently in the timolol solution group than in the timolol GS group (P = 0.04). At week 12, the decrease in mean heart rate at trough (hour 0) was significantly less for patients in the timolol GS group than for those in the timolol solution group (-1.1 vs -4.2 bpm; P = 0.024). At week 24 (hour 0), the decrease in mean heart rate was less for patients treated with timolol GS 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 week 24 (-3.1 vs -4.7 bpm; P = 0.063). The mean change in blood pressure was not significantly different between treatments. There were no clinically significant 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 effective in lowering IOP as the equivalent concentration of timolol 0.5% solution administered twice daily in patients with ocular hypertension or open-angle glaucoma.
Shedden
A
A
Department of Ophthalmic Clinical Research, Merck Research Laboratories, West Point, Pennsylvania, USA.
Laurence
J
J
Tipping
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005782:Gels; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy*; D009883:Ophthalmic Solutions; D013999:Timolol / Q000008:administration & dosage*
D000959:Antihypertensive Agents; D005782:Gels; D009883:Ophthalmic Solutions; D013999:Timolol