Twice-Daily Brinzolamide/Brimonidine Fixed Combination versus Brinzolamide or Brimonidine in Open-Angle Glaucoma or Ocular Hypertension


      To compare the intraocular pressure (IOP)-lowering efficacy and safety of brinzolamide 1% and brimonidine 0.2% fixed combination (BBFC) with that of brinzolamide 1% or brimonidine 0.2% monotherapy, all dosed 2 times per day (BID).


      Six-month, phase 3, randomized, multicenter, double-masked clinical trial.


      A total of 560 patients with primary open-angle glaucoma or ocular hypertension who had insufficient IOP reduction with their current therapeutic regimen or who were receiving ≥2 IOP-lowering medications.


      Patients received BBFC (n = 193), brinzolamide 1% (n = 192), or brimonidine 0.2% (n = 175) BID.

      Main Outcome Measures

      The primary end point was mean change in diurnal IOP from baseline to month 3. Supportive end points included mean diurnal IOP change from baseline at week 2, week 6, and month 6; and mean IOP, mean IOP change from baseline, mean percentage IOP change from baseline, and percentage of patients with IOP <18 mmHg at week 2, week 6, month 3, and month 6 at each assessment time point (i.e., 9 am, 11 am, and 4 pm). Adverse events were recorded throughout the study.


      Baseline diurnal IOP was similar among groups (mean ± standard deviation: BBFC, 25.9±0.19 mmHg; brinzolamide, 25.9±0.20 mmHg; brimonidine, 26.0±0.19 mmHg). At month 3, BBFC lowered mean diurnal IOP from baseline to a significantly greater extent than brinzolamide (least squares [LS] mean difference: −1.4 mmHg; P < 0.0001; t test) and brimonidine (LS mean difference: −1.5 mmHg; P < 0.0001). All supportive end points corroborated the results of the primary efficacy analysis. Mean percentage reductions in IOP from baseline were 26.7% to 36.0% with BBFC, 22.4% to 27.9% with brinzolamide, and 20.6% to 31.3% with brimonidine. The most common adverse drug reactions were ocular side effects, including hyperemia, blurred vision, allergic-type reactions, and discomfort. The incidence of hyperemia of the eye was slightly lower with brinzolamide than with BBFC and brimonidine, whereas blurred vision and ocular discomfort were slightly more common with BBFC than with brinzolamide or brimonidine.


      Brinzolamide 1% and brimonidine 0.2% fixed combination administered BID had a significantly greater IOP-lowering effect than either brinzolamide or brimonidine alone and displayed a safety profile consistent with its individual components.

      Abbreviations and Acronyms:

      AE ( adverse event), BBFC ( brinzolamide 1% and brimonidine 0.2% fixed combination), BCVA ( best-corrected visual acuity), BID ( 2 times per day), IOP ( intraocular pressure), ITT ( intent-to-treat), LS ( least squares), SAE ( serious adverse event), SD ( standard deviation), TID ( 3 times per day)
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        • European Glaucoma Society
        Terminology and Guidelines for Glaucoma.
        3rd ed. Editrice DOGMA, Savona, Italy2008: 122-145 (Available at:) (Accessed June 9, 2014)
        • McCarty C.A.
        • Mukesh B.N.
        • Kitchner T.E.
        • et al.
        Intraocular pressure response to medication in a clinical setting: the Marshfield Clinic Personalized Medicine Research Project.
        J Glaucoma. 2008; 17: 372-377
        • Vorwerk C.
        • Thelen U.
        • Buchholz P.
        • Kimmich F.
        Treatment of glaucoma patients with insufficient intraocular pressure control: a survey of German ophthalmologists in private practice.
        Curr Med Res Opin. 2008; 24: 1295-1301
        • Lee P.P.
        • Walt J.G.
        • Chiang T.H.
        • et al.
        A gap analysis approach to assess patient persistence with glaucoma medication.
        Am J Ophthalmol. 2007; 144: 520-524
        • Higginbotham E.J.
        • Hansen J.
        • Davis E.J.
        • et al.
        Glaucoma medication persistence with a fixed combination versus multiple bottles.
        Curr Med Res Opin. 2009; 25: 2543-2547
        • Higginbotham E.J.
        • Olander K.W.
        • Kim E.E.
        • et al.
        • United States Fixed-Combination Study Group
        Fixed combination of latanoprost and timolol vs individual components for primary open-angle glaucoma or ocular hypertension: a randomized, double-masked study.
        Arch Ophthalmol. 2010; 128: 165-172
        • Katz G.
        • Dubiner H.
        • Samples J.
        • et al.
        Three-month randomized trial of fixed-combination brinzolamide, 1%, and brimonidine, 0.2%.
        JAMA Ophthalmol. 2013; 131: 724-730
        • Nguyen Q.H.
        • McMenemy M.G.
        • Realini T.
        • et al.
        Phase 3 randomized 3-month trial with an ongoing 3-month safety extension of fixed-combination brinzolamide 1%/brimonidine 0.2%.
        J Ocul Pharmacol Ther. 2013; 29: 290-297
        • Whitson J.T.
        • Realini T.
        • Nguyen Q.H.
        • et al.
        Six-month results from a phase III randomized trial of fixed-combination brinzolamide 1% + brimonidine 0.2% versus brinzolamide or brimonidine monotherapy in glaucoma or ocular hypertension.
        Clin Ophthalmol. 2013; 7: 1053-1060
        • Realini T.
        • Nguyen Q.H.
        • Katz G.
        • Dubiner H.
        Fixed-combination brinzolamide 1%/brimonidine 0.2% vs monotherapy with brinzolamide or brimonidine in patients with open-angle glaucoma or ocular hypertension: results of a pooled analysis of two phase 3 studies.
        Eye (Lond). 2013; 27: 841-847
        • Kerr N.M.
        • Patel H.Y.
        • Chew S.S.
        • et al.
        Patient satisfaction with topical ocular hypotensives.
        Clin Experiment Ophthalmol. 2013; 41: 27-35
        • Sleath B.
        • Robin A.L.
        • Covert D.
        • et al.
        Patient-reported behavior and problems in using glaucoma medications.
        Ophthalmology. 2006; 113: 431-436
        • Djafari F.
        • Lesk M.R.
        • Harasymowycz P.J.
        • et al.
        Determinants of adherence to glaucoma medical therapy in a long-term patient population.
        J Glaucoma. 2009; 18: 238-243
        • Olthoff C.M.
        • Schouten J.S.
        • van de Borne B.W.
        • Webers C.A.
        Noncompliance with ocular hypotensive treatment in patients with glaucoma or ocular hypertension: an evidence-based review.
        Ophthalmology. 2005; 112: 953-961
        • Chrai S.S.
        • Makoid M.C.
        • Eriksen S.P.
        • Robinson J.R.
        Drop size and initial dosing frequency problems of topically applied ophthalmic drugs.
        J Pharm Sci. 1974; 63: 333-338
        • Pisella P.J.
        • Pouliquen P.
        • Baudouin C.
        Prevalence of ocular symptoms and signs with preserved and preservative free glaucoma medication.
        Br J Ophthalmol. 2002; 86: 418-423
        • Higginbotham E.J.
        Considerations in glaucoma therapy: fixed combinations versus their component medications.
        Clin Ophthalmol. 2010; 4: 1-9
        • van der Valk R.
        • Webers C.A.
        • Schouten J.S.
        • et al.
        Intraocular pressure-lowering effects of all commonly used glaucoma drugs: a meta-analysis of randomized clinical trials.
        Ophthalmology. 2005; 112: 1177-1185

      Linked Article

      • Corrigendum
        OphthalmologyVol. 122Issue 10
        • In Brief
          With apologies from the authors, the publication titled “Twice-Daily Brinzolamide/Brimonidine Fixed Combination versus Brinzolamide or Brimonidine in Open-Angle Glaucoma or Ocular Hypertension,” (Ophthalmology 2014;121:2348-55) had an error.
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