Robert N Weinreb1, Jason Bacharach2, Robert D Fechtner3, Malik Y Kahook4, David Wirta5, Steve Burmaster6, Xiangyi Meng7, Douglas A Hubatsch6. 1. Hamilton Glaucoma Center and Shiley Eye Institute, University of California San Diego, San Diego, California. Electronic address: hiiop@aol.com. 2. North Bay Eye Associates Inc., Petaluma, California. 3. Department of Ophthalmology, SUNY Upstate Medical University, Syracuse, New York. 4. Department of Ophthalmology, University of Colorado School of Medicine, Aurora, Colorado. 5. Aesthetic Eye Care Institute & Eye Research Foundation, Newport Beach, California. 6. Novartis Pharmaceuticals Corporation, Fort Worth, Texas. 7. Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
Abstract
PURPOSE: To determine the intraocular pressure (IOP)-lowering effect of fixed-combination brinzolamide 1%/brimonidine 0.2% (BBFC) over a 24-hour period. DESIGN: Prospective, multicenter, double-masked, parallel-group clinical trial conducted at 16 academic and nonacademic sites in the United States. PARTICIPANTS: 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. METHODS: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. MAIN OUTCOME MEASURE: Mean change from baseline in 24-hour IOP at week 4. RESULTS: 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. CONCLUSIONS: 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.
RCT Entities:
PURPOSE: To determine the intraocular pressure (IOP)-lowering effect of fixed-combination brinzolamide 1%/brimonidine 0.2% (BBFC) over a 24-hour period. DESIGN: Prospective, multicenter, double-masked, parallel-group clinical trial conducted at 16 academic and nonacademic sites in the United States. PARTICIPANTS: 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. METHODS: 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. MAIN OUTCOME MEASURE: Mean change from baseline in 24-hour IOP at week 4. RESULTS: 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. CONCLUSIONS: 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.