Efficacy and Safety of a Fixed-Dose Combination of Brinzolamide 1%/Timolol 0.5% vs. Dorzolamide 2%/Timolol 0.5% in Indian Patients With Primary Open-Angle Glaucoma or Ocular Hypertension: A Randomized Phase 3 Study.

Introduction Fixed-dose combinations (FDCs) have the potential in glaucoma management to improve efficacy due to the complementary mechanism of action of the drugs as well as compliance while reducing adverse effects by minimizing exposure to preservatives and the financial burden on the patients. FDC of brinzolamide/timolol has demonstrated efficacy and safety in multinational phase 3 studies in primary open-angle glaucoma (POAG) and ocular hypertension. However, efficacy and safety in the Indian population are not known. This study compared the efficacy and safety of FDC brinzolamide 1%/timolol 0.5% with FDC dorzolamide 2%/timolol 0.5% in Indian patients with POAG or ocular hypertension. Material and methods This 12-week randomized, phase 3, open-label, comparative, multicentric study was conducted on 221 subjects at nine sites in India, with assessments done at baseline and weeks 4, 8, and 12. Patients with intraocular pressure (IOP) of 24-36 mmHg of the affected eye(s), either newly diagnosed or inadequately controlled on mono-therapy of carbonic anhydrase inhibitor, beta-blocker, or any other IOP-lowering therapy, were included. Patients were randomly assigned to receive either FDC of brinzolamide 1%/timolol 0.5% (n = 111) or FDC of dorzolamide 2%/timolol 0.5% (n = 110). Primary efficacy was a noninferiority comparison of mean change in two-hour IOP and zero-hour IOP at the end of treatment compared to the respective baseline IOP. Safety was analyzed by comparing the frequency of the observed adverse events (AEs) between the two groups. Results FDC brinzolamide/timolol produced comparable and non-inferior IOP-lowering efficacy to FDC dorzolamide/timolol. The IOP reductions ranged from 6.55 to 8.36 mmHg in FDC brinzolamide/timolol group and from 5.37 to 7.55 mmHg in FDC dorzolamide/timolol group. Fewer subjects in FDC brinzolamide/timolol group experienced ocular AEs as compared with FDC dorzolamide/timolol group (9.9% vs. 26.4%), especially ocular hyperemia (2.7% vs. 22.7%). Conclusion FDC of brinzolamide 1%/timolol 0.5% affords an ocular comfort advantage with a clinically meaningful reduction in IOP that was non-inferior to FDC of dorzolamide 2%/timolol 0.5% in Indian patients with POAG and ocular hypertension.