A Masked,Randomized,Phase 3 Comparison of Triple Fixed-Combination Bimatoprost/Brimonidine/Timolol versus Fixed-Combination Brimonidine/Timolol for Lowering Intraocular Pressure

Objective. to evaluate the efficacy and safety of triple fixed-combination bimatoprost 0.01%/brimonidine 0.15%/timolol 0.5% (tfc) versus dual fixed-combination brimonidine 0.2%/timolol 0.5% (dfc) in primary open-angle glaucoma and ocular hypertension. methods. patients with intraocular pressure (iop) ≥23 and ≤34 mmhg were randomized to twice-daily tfc or dfc. the primary variable is the change in worse eye mean iop from baseline at week 12 (modified intent-to-treat (mitt) population). secondary endpoints are mean iop and mean change from baseline at weeks 1,2,4,8,and 12 (mitt population). tfc superiority was demonstrated if the primary variable favored tfc (p≤0.05). sensitivity analyses were conducted,and safety was assessed at all visits. results. tfc (n=93) provided greater iop reductions from baseline than dfc (n=97) at week 12 (treatment difference,0.85 mmhg; p=0.028) and all other visits. tfc was also superior to dfc in patients with high baseline iop (i.e.,iop ≥ 25 mmhg; p≤0.011). conjunctival hyperemia,ocular irritation,and dry eye were reported more often with tfc (p≤0.016); however,discontinuations for ocular adverse events were similar between treatments. conclusions. tfc demonstrated iop-lowering benefits that outweigh the risk of predominantly mild ocular side effects,which may be particularly relevant in patients who require greater iop lowering to prevent/delay disease progression. this trial is registered with clinicaltrials.gov registry number: nct01241240. © 2017 curt hartleben et al.