Comparison of the efficacy and tolerability of preservative-free and preservative-containing formulations of the dorzolamide/timolol fixed combination (COSOPT™) in patients with elevated intraocular pressure in a randomized clinical trial

• Published in: Graefe's archive for clinical and experimental ophthalmology Vol. 248; no. 12; pp. 1757 - 1764
• Main Authors: Shedden, Arthur, Adamsons, Ingrid A., Getson, Albert J., Laurence, Jean K., Lines, Christopher R., Hewitt, David J., Ho, Tony W.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.12.2010; Springer Nature B.V
• Subjects: Antihypertensive Agents - administration & dosage; Antihypertensive Agents - therapeutic use; Double-Blind Method; Drug Combinations; Female; Glaucoma; Glaucoma, Open-Angle - drug therapy; Humans; Intraocular Pressure - drug effects; Male; Medicine; Medicine & Public Health; Middle Aged; Ocular Hypertension - drug therapy; Ophthalmology; Preservatives, Pharmaceutical - adverse effects; Preservatives, Pharmaceutical - therapeutic use; Sulfonamides - adverse effects; Sulfonamides - therapeutic use; Thiophenes - adverse effects; Thiophenes - therapeutic use; Timolol - adverse effects; Timolol - therapeutic use; Tonometry, Ocular; Treatment Outcome; Glaucoma; Dorzolamide; Ocular hypertension; COSOPT; Benzalkonium chloride; Timolol; Intraocular pressure
• ISSN: 0721-832X; 1435-702X; 1435-702X
• DOI: 10.1007/s00417-010-1397-7

Background The aim of this study was to compare the efficacy and tolerability of preservative-free (PF) and preservative-containing (PC) formulations of the dorzolamide/timolol fixed combination (COSOPT™) in patients with elevated intraocular pressure (IOP). Methods A parallel, randomized, double-masked study was conducted. After a 3-week run-in on timolol, patients with ocular hypertension, as confirmed by an IOP ≥22 mmHg, were randomized 1:1 to receive PF or PC dorzolamide/timolol twice daily for 12 weeks. IOP was measured at hour 0 (drug trough) and hour 2 (drug peak) at baseline (last day of 3-week timolol run-in), and weeks 2, 6 and 12. Results A total of 261 patients were randomized. Mean baseline IOPs were 23.7 mmHg for both treatments at hour 0 and 21.2 mmHg for PF dorzolamide/timolol and 21.4 mmHg for PC dorzolamide/timolol at hour 2. At all study time points (trough and peak at weeks 2, 6, and 12), the difference between treatments in mean change from baseline IOP was <0.5 mmHg. The 95% confidence intervals for the estimated treatment difference (PF minus PC) in mean change from baseline IOP at week 12 was −0.86 to 0.23 mmHg for trough (primary endpoint) and −0.39 to 0.67 mmHg for peak (secondary endpoint). The most common adverse events were ocular burning/stinging, reported by 16.0% and 21.5% of patients receiving PF and PC dorzolamide/timolol respectively, and taste perversion, reported by 3.1% and 5.4% of patients receiving PF and PC dorzolamide/timolol respectively. Conclusions In patients with elevated IOP, PF and PC dorzolamide/timolol were equivalent in efficacy for change in trough and peak IOP, and had generally similar tolerability.