24-Hour Intraocular Pressure Control with Fixed-dose Combination Brinzolamide 1%/Brimonidine 0.2%: A Multicenter, Randomized Trial

• Published in: Ophthalmology (Rochester, Minn.) Vol. 126; no. 8; p. 1095
• Main Authors: Weinreb, Robert N, Bacharach, Jason, Fechtner, Robert D, Kahook, Malik Y, Wirta, David, Burmaster, Steve, Meng, Xiangyi, Hubatsch, Douglas A
• Format: Journal Article
• Language: English
• Published: United States 01.08.2019
• Subjects: Aged; Antihypertensive Agents - therapeutic use; Brimonidine Tartrate - therapeutic use; Carbonic Anhydrase Inhibitors - therapeutic use; Double-Blind Method; Drug Therapy, Combination; Female; Glaucoma, Open-Angle - drug therapy; Glaucoma, Open-Angle - physiopathology; Humans; Intraocular Pressure - drug effects; Male; Middle Aged; Ocular Hypertension - drug therapy; Ocular Hypertension - physiopathology; Prospective Studies; Sulfonamides - therapeutic use; Thiazines - therapeutic use
• ISSN: 1549-4713; 1549-4713
• DOI: 10.1016/j.ophtha.2018.10.040

To determine the intraocular pressure (IOP)-lowering effect of fixed-combination brinzolamide 1%/brimonidine 0.2% (BBFC) over a 24-hour period. Prospective, multicenter, double-masked, parallel-group clinical trial conducted at 16 academic and nonacademic sites in the United States. Subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT) aged ≥18 years with mean baseline IOP measurements in at least 1 eye of ≥21 and <28 mmHg. Duplicate mean pneumatonometer IOP measurements were collected every 2 hours over a 24-hour period in controlled light conditions in overnight facilities. Daytime (8 am-8 pm) and nocturnal (10 pm-6 am) IOP measurements were collected in a sitting or supine position, respectively. Baseline 24-hour IOP was measured in untreated subjects after a washout (up to 4 weeks) and eligibility phase. After the baseline visit, participants were randomized 1:1 to receive masked BBFC or vehicle, 1 drop 3 times daily (8 am, 3 pm, and 10 pm) for 4 weeks. At week 4, IOP measurements were repeated in both groups under the same conditions. Mean change from baseline in 24-hour IOP at week 4. Of 125 participants randomized, 123 (98%; BBFC, n = 62; vehicle, n = 61) completed the study. No subjects randomized to BBFC discontinued the study. At week 4, BBFC-treated eyes had significantly reduced mean 24-hour IOP vs. vehicle (least squares mean difference [95% confidence interval]: -2.5 [-3.3, -1.7]; P < 0.001); daytime (-3.4 [-4.3, -2.6]; P < 0.001) and nocturnal (-1.2 [-2.3, 0.0]; P = 0.053) reductions were observed. Mean change from baseline was significantly different between BBFC- and vehicle-treated eyes at all daytime points and 3 of 5 nocturnal time points (10 pm, 12 am, and 6 am; secondary end point). The frequency of adverse events was similar between treatment groups; in the BBFC arm, ocular hyperemia, corneal abrasion, and dysgeusia were the most frequently reported, consistent with events described in the drug label. This large, multicenter study of 24-hour IOP control with BBFC met its primary end point; BBFC demonstrated significantly superior 24-hour IOP-lowering efficacy versus vehicle after 4 weeks of 3-times-daily treatment in subjects with OAG or OHT.