Dataset Information

Comparison of the Intraocular Pressure-Lowering Efficacy and Safety of the Brinzolamide/Brimonidine Fixed-Dose Combination versus Concomitant Use of Brinzolamide and Brimonidine for Management of Open-Angle Glaucoma or Ocular Hypertension.

ABSTRACT: Objective:To demonstrate that the intraocular pressure (IOP)-lowering efficacy of a twice-daily brinzolamide 10 mg/mL (BRINZ)/brimonidine 2 mg/mL (BRIM) fixed-dose combination (BBFC) was non-inferior to its individual components (BRINZ+BRIM) dosed concomitantly in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Safety was also evaluated. Methods and Analysis:This was a Phase III, multicenter, observer-masked study in patients from China, Russia and Taiwan. Patients aged ?18 years with a mean IOP ?21 mmHg and ?36 mmHg in the same eye after washout of other IOP-lowering medications were included. Eligible patients were randomized (1:1) to receive BBFC or BRIZ+BRIM eye drops twice daily for 3 months. The primary endpoint was the mean change in diurnal IOP (averaged over 09:00, +2 h, and +7 h) from baseline to Month 3. Adverse events (AEs) were recorded throughout the study. Results:The per-protocol set included 349 patients (BBFC, n=172; BRINZ+BRIM, n=177). The mean±standard deviation diurnal IOP at baseline was 24.6±2.66 mmHg in both groups. At Month 3, the least square mean±standard error change in diurnal IOP from baseline was -7.2±0.34 mmHg and -7.3±0.34 mmHg with BBFC and BRINZ+BRIM, respectively (between-group difference: 0.1 mmHg [95% CI -0.5, 0.7]). In the BBFC and BRINZ+BRIM groups, 53.3% and 55.0% of patients achieved a diurnal IOP <18 mmHg, and 43.2% and 37.4% of patients, respectively, achieved a mean diurnal IOP reduction >30% from baseline at Month 3. Ocular AEs were reported in 28.7% (BBFC) and 22.5% (BRINZ+BRIM) of patients; conjunctival hyperemia was the most frequent ocular AE (BBFC, 6.4%; BRINZ+BRIM, 6.8%). Non-ocular AEs were reported in 32.4% (BBFC) and 30.4% (BRINZ+BRIM) of patients. Conclusion:The study findings demonstrate that the efficacy of twice-daily BBFC was non-inferior to BRINZ+BRIM in patients with OAG/OHT. The safety profile of BBFC was similar to that of BRINZ+BRIM.

SUBMITTER: Wang N

PROVIDER: S-EPMC6986681 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Comparison of the Intraocular Pressure-Lowering Efficacy and Safety of the Brinzolamide/Brimonidine Fixed-Dose Combination versus Concomitant Use of Brinzolamide and Brimonidine for Management of Open-Angle Glaucoma or Ocular Hypertension.

Wang Ningli N Lu Da-Wen DW Pan Yingzi Y Astakhov Yury Y Iureva Tatyana T Adewale Adeniyi A Walker Thomas M TM

Clinical ophthalmology (Auckland, N.Z.) 20200123

<h4>Objective</h4>To demonstrate that the intraocular pressure (IOP)-lowering efficacy of a twice-daily brinzolamide 10 mg/mL (BRINZ)/brimonidine 2 mg/mL (BRIM) fixed-dose combination (BBFC) was non-inferior to its individual components (BRINZ+BRIM) dosed concomitantly in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Safety was also evaluated.<h4>Methods and analysis</h4>This was a Phase III, multicenter, observer-masked study in patients from China, Russia and Taiwan. Pa ...[more]

PMID: 32158181

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Project description:IntroductionFixed-combination intraocular pressure (IOP)-lowering medications simplify treatment regimens for patients requiring 2 ocular hypotensive agents to maintain sufficiently low IOP. The aim of this study was to evaluate the safety and efficacy of fixed-combination brinzolamide 1%/brimonidine 0.2% (BBFC) versus concomitant administration of brinzolamide 1% plus brimonidine 0.2% (BRINZ + BRIM) in patients with open-angle glaucoma or ocular hypertension.MethodsThis was a prospective, phase 3, multicenter, double-masked, 6-month trial. Patients who had insufficient IOP control with monotherapy or who were receiving 2 IOP-lowering medications were randomized 1:1 to receive twice-daily BBFC or BRINZ + BRIM. IOP was assessed at 9 a.m. and 11 a.m. during week 2, week 6, month 3, and month 6 visits. The primary efficacy endpoint was mean diurnal IOP change from baseline to month 3; noninferiority was concluded if the upper limit of the 95% CI of the between-group difference was <1.5 mmHg. Supportive endpoints included mean IOP, IOP change from baseline, and percentage of patients with IOP <18 mmHg. Adverse events were recorded.ResultsThe mean diurnal IOP change from baseline with BBFC (least squares mean ± standard error -8.5 ± 0.16 mmHg) was noninferior to that with BRINZ + BRIM (-8.3 ± 0.16 mmHg; mean difference -0.1 mmHg; 95% CI -0.5 to 0.2 mmHg). The upper limits of the 95% CIs were <1.5 mmHg at all time points. Decreases from baseline >8 mmHg were observed for least squares mean diurnal IOP in both groups as early as week 2 and continued to the end of the study. The results of all other supportive endpoints were similar to the primary efficacy endpoint. The most common ocular adverse drug reactions were hyperemia of the eye (reported as ocular or conjunctival hyperemia), visual disturbances, ocular allergic reactions, and ocular discomfort. Common systemic adverse drug reactions included dysgeusia, oral dryness, and fatigue/drowsiness.ConclusionBrinzolamide 1%/brimonidine 0.2% fixed combination was as well tolerated and effective as concomitant therapy with its components. BBFC reduces treatment burden in patients who require multiple IOP-lowering medications.

Project description:IntroductionFixed-combination glaucoma medications are commonly used to achieve target intraocular pressure (IOP) reduction in patients uncontrolled with monotherapy; however, ocular discomfort associated with eye drops can decrease adherence. This study assessed the efficacy and tolerability of twice-daily fixed-combination brinzolamide 1%/timolol 0.5% (BRINZ/TIM-FC) in Latin American patients transitioned from fixed-combination brimonidine 0.2%/timolol 0.5% (BRIM/TIM-FC) because of insufficient IOP control or treatment intolerance.MethodsThis 8-week, open-label, prospective study was conducted at six sites in Argentina, Chile, and Mexico. Enrolled patients were aged ≥18 years with open-angle glaucoma (including primary, exfoliative, or pigment-dispersion glaucoma) or ocular hypertension with IOP of 19-35 mmHg in ≥1 eye at baseline (on BRIM/TIM-FC). Patients self-administered BRINZ/TIM-FC to both eyes at 8 a.m. and 8 p.m. daily for 8 weeks. The primary and secondary efficacy endpoints were mean IOP change from baseline at week 8 and percentage of patients achieving target IOP (≤18 mmHg) at week 8, respectively. Exploratory endpoints included patient and investigator preference for treatment at week 8. Adverse events (AEs) were assessed as the safety endpoint.ResultsFifty patients (mean ± SD age, 66.7 ± 11.5 years) received BRINZ/TIM-FC, and 49 were included in the intent-to-treat population. Mean ± SD IOP was significantly reduced from baseline after 8 weeks of treatment with BRINZ/TIM-FC (-3.6 ± 3.0 mmHg; P < 0.0001, Wilcoxon signed-rank test; 17.1% reduction). Overall, 55.3% of patients achieved IOP ≤18 mmHg at week 8. Significantly more patients (89.4%) and investigators (95.7%) preferred BRINZ/TIM-FC to BRIM/TIM-FC (both P < 0.0001, exact binomial test). Of the 13 AEs observed, 8 were related to BRINZ/TIM-FC; the most common treatment-related AEs were eye irritation (n = 4) and abnormal sensation in the eye (n = 2).ConclusionBRINZ/TIM-FC provides an effective and well-tolerated treatment option for patients transitioned from BRIM/TIM-FC.

Project description:ObjectiveTo assess ocular discomfort upon instillation and patient preference for brinzolamide/timolol relative to dorzolamide/timolol, in patients with open-angle glaucoma or ocular hypertension.MethodsThis was a multicenter, prospective, patient-masked, randomized, crossover study. On day 0, patients received one drop of brinzolamide/timolol in one eye and one drop of dorzolamide/timolol in the contralateral eye. On day 1, patients were randomly assigned to receive one drop of either brinzolamide/timolol or dorzolamide/timolol in both eyes; on day 2, patients received one drop of the alternate treatment in both eyes. Measures included a patient preference question on day 2 (primary) and mean ocular discomfort scale scores on days 1 and 2 (secondary). Safety assessments included adverse events, visual acuity, and slit-lamp examinations.ResultsOf 120 patients who enrolled, 115 completed the study. Of these, 112 patients instilled both medications and expressed a study medication preference on day 2. A significantly greater percentage preferred brinzolamide/timolol to dorzolamide/timolol (67.0% versus 30.4%; P < 0.001). The ocular discomfort (expressed as mean [standard deviation]) with brinzolamide/timolol was significantly lower than with dorzolamide/timolol (day 2:1.9 [2.3] versus 3.7 [2.8], respectively [P = 0.0003]; both days combined: 2.1 [2.5] versus 3.5 [2.9], respectively [P = 0.00014]). On day 1, five patients receiving brinzolamide/timolol reported five nonserious adverse events (AEs): flu (n = 1), bitter taste (n = 2), and headache (n = 2). Four events, bitter taste (two events) and headache (two events), were considered related to brinzolamide/timolol. Events were mild in intensity, except bitter taste of moderate intensity reported by one patient. No AEs were reported at day 2. All AEs resolved without additional treatment. No clinically relevant changes from baseline were observed in best-corrected visual acuity or slit-lamp examinations of ocular signs.ConclusionPatients had less discomfort with brinzolamide/timolol than with dorzolamide/timolol, and more expressed a preference for brinzolamide/timolol. Both treatments were generally safe and well tolerated.

Project description:BACKGROUND:Fixed-combination ocular hypotensives have multiple advantages, but triple-therapy dorzolamide/brimonidine/timolol (dorz/brim/tim) is only available in Latin and South America, and information on its relative efficacy is limited. This study compares the efficacy and tolerability of fixed-combination bimatoprost/timolol (bim/tim) and dorz/brim/tim in Mexican patients with primary open-angle glaucoma or ocular hypertension. METHODS:In this investigator-masked, crossover study, patients with unmet target intraocular pressure (IOP) on once-daily bim/tim or twice-daily dorz/brim/tim received the opposite medication for 3 months before returning to their pre-baseline medication for 3 months. IOP was evaluated before and after morning instillation at months 2, 3, 5 and 6. Primary endpoints were mean IOP change and Ocular Surface Disease Index© (OSDI) score at each visit. The intent-to-treat population was the a priori analysis population, but due to the number of discontinuations, the per-protocol and intent-to-treat populations were used for the primary efficacy and sensitivity analyses, respectively. RESULTS:Seventy-eight and 56 patients were included in the intent-to-treat and per-protocol populations, respectively. At month 3, statistically significant IOP reductions from baseline were observed in the bim/tim (P?<?0.01) and dorz/brim/tim (P?<?0.0001) groups, regardless of assessment time. At month 6, patients returned to bim/tim exhibited no significant IOP increase (regardless of assessment time), but patients returned to dorz/brim/tim exhibited a statistically significant IOP increase (P?<?0.001) when assessed before instillation of study treatment. Results were similar in both intent-to-treat and per-protocol analysis populations. In the per-protocol analysis, 70% of patients on bim/tim at month 3 had an IOP <14 mm Hg, which declined to 58% (P?=?0.0061) at month 6 (ie, after 3 months of dorz/brim/tim treatment). In patients receiving dorz/brim/tim at month 3, 38% had an IOP <14 mm Hg, which remained comparable after return to bim/tim. OSDI scores and incidence of adverse events were similar in both groups. CONCLUSIONS:In this first direct comparison of the efficacy of dorz/brim/tim and bim/tim, patients switched from dorz/brim/tim to bim/tim demonstrated improved/lower IOP; when returned to dorz/brim/tim, IOP increased to levels seen at study initiation, suggesting that once-daily bim/tim may have greater IOP-lowering efficacy. Both bim/tim and dorz/brim/tim were well tolerated with minimal ocular surface damage. TRIAL REGISTRATION:ClinicalTrials.gov: NCT01737853 (registered October 9, 2012).

Dataset Information

Comparison of the Intraocular Pressure-Lowering Efficacy and Safety of the Brinzolamide/Brimonidine Fixed-Dose Combination versus Concomitant Use of Brinzolamide and Brimonidine for Management of Open-Angle Glaucoma or Ocular Hypertension.

Publications

Comparison of the Intraocular Pressure-Lowering Efficacy and Safety of the Brinzolamide/Brimonidine Fixed-Dose Combination versus Concomitant Use of Brinzolamide and Brimonidine for Management of Open-Angle Glaucoma or Ocular Hypertension.

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