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.