Three-month, randomized, parallel-group comparison of brimonidine–timolol versus dorzolamide–timolol fixed-combination therapy

ABSTRACT

Objective: Fixed combinations of 0.2% brimonidine–0.5% timolol and 2% dorzolamide–0.5% timolol are used to lower intraocular pressure (IOP). The objective of this study was to evaluate the IOP-lowering efficacy and ocular tolerability of brimonidine–timolol compared with dorzolamide–timolol when used as monotherapy or as adjunctive therapy to a prostaglandin analog (PGA) in patients with glaucoma or ocular hypertension.

Study design and methods: Pooled data analysis of two randomized, investigator-masked, 3-month, parallel-group studies with identical protocols (ten sites). In all, 180 patients with open-angle glaucoma or ocular hypertension who were in need of lower IOP received topical brimonidine–timolol BID or dorzolamide–timolol BID as monotherapy (n = 101) or as adjunctive therapy to a PGA (latanoprost, bimatoprost, or travoprost) (n = 79).

Clinical trial registration: The studies are registered with the identifiers NCT00822081 and NCT00822055 at http://www.clinicaltrials.gov.

Main outcome measures: IOP was measured at 10 a.m. (peak effect) at baseline and at months 1 and 3. Tolerability/comfort was evaluated using a patient questionnaire.

Results: There were no statistically significant between-group differences in patient demographics. Most patients were Caucasian, and the mean age was 68 years. There were also no statistically significant differences between treatment groups in baseline IOP. At month 3, the mean (SD) reduction from baseline IOP for patients on fixed-combination monotherapy was 7.7 (4.2) mmHg (32.3%) with brimonidine–timolol versus 6.7 (5.0) mmHg (26.1%) with dorzolamide–timolol (p = 0.040). The mean reduction from PGA-treated baseline IOP for patients on fixed-combination adjunctive therapy was 6.9 (4.8) mmHg (29.3%) with brimonidine–timolol versus 5.2 (3.7) mmHg (23.5%) with dorzolamide–timolol (p = 0.213). Patients on brimonidine–timolol reported less burning (p < 0.001), stinging (p < 0.001), and unusual taste (p < 0.001) than patients on dorzolamide–timolol.

Conclusions: Fixed-combination brimonidine–timolol provided the same or greater IOP lowering compared with fixed-combination dorzolamide–timolol. Both fixed-combination medications were safe and well-tolerated. Brimonidine–timolol received higher ratings of ocular comfort than dorzolamide–timolol. The duration of the studies was 3 months, and additional studies will be needed to compare the efficacy and tolerability of brimonidine–timolol and dorzolamide–timolol during long-term treatment.

Key words: :

• Brimonidine
• Dorzolamide
• Fixed combination
• Glaucoma
• Intraocular pressure
• Timolol

Transparency

Declaration of funding

Study 1 was funded by an unrestricted educational grant from Allergan, Inc. Study 2 was sponsored by Allergan.

Declaration of financial/other relationships

S.S. and D.A.H. have disclosed that they are employees of Allergan. D.R.N. has disclosed that he is a consultant for, or receives funding for speaking and/or travel from, the following companies: Allergan, AMO, Bausch & Lomb, Merck Frosst, Novartis, and Oculus. D.B.Y. has disclosed that he is a consultant for, or receives funding for speaking and/or travel from, the following companies: Alcon, Allergan, Imed Pharma, Pfizer, and Rayner. J.-P.C. has disclosed that he has no relevant financial interests. R.L.P. has disclosed that he is a consultant for Alcon, Allergan, Merck Frosst, and Novartis.

All peer reviewers receive honoraria from CMRO for their review work. Peer Reviewer 1 and Peer Reviewer 2 have disclosed that they have no relevant financial relationships.

Acknowledgment

The authors thank Nicolas Le Gall, MSc, ethica Clinical Research Inc., Dorval, QC, Canada, for the statistical analyses of the pooled study data, and Kate Ivins, PhD, for medical writing assistance.

Principal investigators

Study 1: D.R.N. Study 2: Iqbal K. Ahmed, MD, FRCSC, Brampton, ON, Canada; Jeffrey D. Chambers, MD, FRCSC, Kelowna, BC, Canada; J-P.C.; Andrew C.S. Crichton, MD, FRCSC, Calgary, AB, Canada; Leslie S. Landecker, MD, Newmarket, ON, Canada; Marcelo T. Nicolela, MD, Halifax, NS, Canada; D.R.N.; Carl W. Peters, MD, FRCSC, Dipl ABO, Penticton, BC, Canada; R.L.P.; D.B.Y.

Notes

* The results of this pooled data analysis were presented in part at the 111th Annual Meeting of the American Academy of Ophthalmology, November 10–13, 2007, New Orleans, LA, USA

* Cosopt is a registered trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA

† Combigan is a registered trademark of Allergan, Inc., Irvine, CA, USA