24-hour control of intraocular pressure with 2% dorzolamide/0.5% timolol fixed-combination ophthalmic solution in open-angle glaucoma^*

ABSTRACT

Objective: To evaluate the 24-hour efficacy and tolerability of 2% dorzolamide/0.5% timolol fixed combination (DTFC) solution in open-angle glaucoma and ocular hypertension.

Research design and methods: Randomized, parallel, doublemasked, multicenter study. Patients with insufficiently controlled intraocular pressure (IOP≥22 mmHg) were randomized to DTFC (N=117) or timolol (N=115). IOP was measured at baseline, 6 weeks, and 8 weeks, with measurements taken at 6 p.m., 8 p.m., 10 p.m., 2 a.m., 6 a.m., 8 a.m., 10 a.m., and 2 p.m.

Main outcome measures: Statistically significant change in IOP from untreated baseline for DTFC at all hours at week 8. Secondary outcome measures included: IOP-lowering at week 6 at all individual time points, change from baseline to 8 weeks in mean daytime IOP (average of 8 a.m., 10 a.m., 2 p.m., 6 p.m., and 8 p.m. IOPs) and night-time IOP (10 p.m., 2 a.m., 6 a.m.), and comparison of DTFC with timolol after 8 weeks.

Results: Patients receiving DTFC had a statistically significant and clinically relevant reduction in IOP at week 8 compared with baseline at all eight time points (p<0.001). Significant IOP reductions were also seen at all time points at week 6 (p<0.001). DTFC significantly lowered mean daytime IOP and night-time IOP (p<0.001 for both). Timolol alone also significantly reduced IOP from baseline at 8 weeks for all diurnal time points, and mean daytime and night-time IOP (p<0.001 for all). Compared with timolol alone, there were significantly greater reductions with DTFC at 10 a.m. (p=0.003) and 2 p.m. (p=0.016), and for mean daytime IOP (p=0.025) at 8 weeks. Significant between-treatment differences were not observed at other time points. Both treatments were well-tolerated, with no differences observed in the safety profiles between the treatment groups.

Conclusions: Both DTFC and timolol provided significant IOP reduction over the entire 24-hour measurement period. timolol during the daytime, but not at night. Although this study was not designed or powered to compare DTFC and timolol, DTFC exhibited greater IOP-lowering than timolol during the daytime, but not at night.

Trial registration: ClinicalTrials.gov identifier: NCT00108017.

Key words: :

• Diurnal rhythm
• Dorzolamide
• Glaucoma
• Ocular hypertension
• Timolol

Acknowledgments

Declaration of interest: This study was funded by Merck & Co., Inc., which participated in the design and conduct of the study; data collection; management, analysis and interpretation; and preparation, review, and approval of the manuscript. RMF reports research funding/grant support from Alcon Laboratories, Inc.; Pfizer Ophthalmics; Eye Technology Ltd; Genaera Corporation; Allergan, Inc.; Merck US Human Health; he is a consultant for Alcon Laboratories, Inc.; Pfizer Ophthalmics; Eye Technology Ltd. He has received lecture fees from Alcon Laboratories, Inc; Pfizer Ophthalmics; Eye Technology Ltd. RHS has received research funding from Merck and is a consultant for Merck. WCS is a consultant for Merck. VAG, GJ, and SSS are employees of Merck & Co. and may potentially own stock and/or hold stock options in the company.

The members of the Protocol 137 Scientific Advisory Committee included: E. R. Craven, D. G. Day, H. B. DuBiner, R. F. Feldman, V. A. Galet, K. Gergich, G. Jia, K. W. Olander, S. S. Smugar, R. H. Stewart, W. C. Stewart, G. C. Thorne, and R. D. Williams.

The authors thank the investigators for the Protocol 137 study: D. E. Beahm, W. F. Davitt, III, R. Evans, R. Hayhurst, B. E. Kanengiser, N. S. Levy, E. B. McLaurin, M. H. Rotberg, H. I. Schenker, D. L. Schwartz, J. H. Tibbetts, and G. B. Walman.

The authors also thank Kevin Gergich, Brenda Ryan, Frank La Barbera, Sheila Aseltine, and Filippa Karcewski for their contributions to the conduct of the study, and to Martha Vollmer for her assistance with the preparation of the manuscript.

Notes

* These data were presented at the American Glaucoma Society meeting, March 1–4, 2007, San Francisco, CA, USA, and at the Association for Research in Vision and Ophthalmology meeting, May 6–10, 2007, Fort Lauderdale, FL, USA