Fixed-combination brimonidine–timolol versus latanoprost in glaucoma and ocular hypertension: a 12-week, randomized, comparison study

Abstract

Objective:

To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of fixed-combination brimonidine 0.2%–timolol 0.5% compared with latanoprost 0.005% in patients with glaucoma or ocular hypertension.

Research design and methods:

This was a prospective, randomized, multicenter, investigator-masked clinical trial. After washout of any previous IOP-lowering medications, patients with IOP of 24 mmHg or higher were randomized to twice-daily fixed-combination brimonidine 0.2%–timolol 0.5% (n = 73) or once-daily latanoprost 0.005% (n = 75, dosed in the evening, with vehicle control in the morning to maintain masking) for 12 weeks. IOP was measured at 8 a.m. (before dosing), 10 a.m., and 3 p.m. at baseline, week 6, and week 12.

Clinical trial registration:

The trial is registered with the identifier 00811564 at http://www.clinicaltrials.gov.

Main outcome measures:

The primary efficacy endpoint was diurnal IOP (averaged over 8 a.m., 10 a.m., and 3 p.m.) at week 12. Safety measures included biomicroscopy.

Results:

There was no statistically significant difference between the treatment groups in mean diurnal IOP at baseline (p = 0.118). At week 12, the mean (SD) diurnal IOP was 17.8 (2.9) mmHg with brimonidine–timolol and 17.9 (3.9) mmHg with latanoprost (p = 0.794). The percentage of patients achieving at least a 20% decrease from baseline diurnal IOP at week 12 was 87.7% in the brimonidine–timolol group and 77.3% in the latanoprost group (p = 0.131). Measured biomicroscopic changes from baseline to week 12 were infrequent in both groups.

Conclusions:

Fixed-combination brimonidine–timolol was as effective as latanoprost in reducing IOP in patients with glaucoma or ocular hypertension. Both treatments demonstrated favorable ocular tolerability. The duration of the study was 12 weeks, and additional studies will be needed to compare the efficacy and safety of fixed-combination brimonidine–timolol and latanoprost during long-term treatment.

Keywords::

• Alpha adrenergic agonist
• Beta-blocker
• Fixed combination
• Glaucoma
• Intraocular pressure (IOP)
• Prostaglandin analog

Transparency

Declaration of funding

This study was sponsored by Allergan, Inc.

Declaration of financial/other relationships

L.J.K., S.H.R., A.J.C. and S.T.S. have no proprietary interest in brimonidine–timolol or Allergan, Inc. L.J.K. and S.T.S. serve as consultants to Allergan and have received research support from Allergan. S.H.R. has received research support from Allergan. A.J.C. has no potential conflicts of interest to disclose. J.M.W., R.M.S., and D.A.H. are employees of Allergan, Inc. and own stock in the company through matching benefits.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

A contract research organization, Janix, LLC (Aliso Viejo, CA, USA) was contracted by Allergan, Inc. to monitor the study and provide data management. Jatinder Singh (Janix, LLC) performed the statistical analysis. Allergan, Inc. provided funding for a freelance medical writer, Kate Ivins, PhD, to assist in the development of the manuscript. Editorial assistance in formatting, proofreading, and copy editing was also provided by SCI Scientific Communications & Information. Allergan, Inc. provided funding to SCI Scientific Communications & Information for support in editing this manuscript. The principal investigators and sites participating in the study were: Jason Bacharach, MD (Petaluma, CA, USA); Andrew J. Cottingham, Jr., MD (San Antonio, TX, USA); Monte S. Dirks, MD (Rapid City, SD, USA); Robert H. Ewing, Jr., MD (Ashland, OR, USA); L. Jay Katz, MD (Philadelphia, PA, USA); Michael S. Korenfeld, MD (Washington, MO, USA); Jeffrey R. Lozier, MD (Poway, CA, USA); Steven T. Simmons, MD (Slingerlands, NY, USA); Dennis Slochower, MD (Philadelphia, PA, USA); Steven H. Rauchman, MD (Mission Hills, CA, USA); Ronald E. Frenkel, MD (Stuart, FL, USA); William B. Trattler, MD (Miami, FL, USA).

The results of this study were presented in part at the ASCRS·ASOA Symposium and Congress; April 9–14, 2010; Boston, MA, USA.

Notes

*Combigan is a registered trade mark of Allergan, Inc., Irvine, CA, USA.

^†Xalatan is a registered trademark of Pfizer Inc., New York, NY, USA.