Introduction
Methods
Study Design and Intervention
Patients
Inclusion criteria |
Understood and provided informed consent |
Aged ≥18 years |
Diagnosed with open-angle glaucoma or ocular hypertension that was insufficiently controlled on monotherapy or being treated with multiple IOP-lowering medications |
Mean IOP measurements for ≥1 eye (the same eye) were 24–36 mmHg at 9 a.m. and 21–36 mmHg at 11 a.m. during both eligibility visits (after the required washout period) |
Mean IOP ≤36 mmHg in both eyes at all time points |
Exclusion criteria |
Pregnant/nursing, planning to become pregnant, or not using adequate birth control during the study |
Schaffer angle grade <2 in either eye (as measured by gonioscopy) |
Cup-to-disc ratio >0.80 (horizontal or vertical measurement) in either eye |
Severe central visual field loss (i.e., sensitivity ≤10 dB in ≥2 of the 4 visual field test points closest to the point of fixation) in either eye |
Unable to safely discontinue IOP-lowering ocular medications per the washout schedule |
Chronic, recurrent, or current severe inflammatory eye disease (i.e., scleritis, uveitis, herpes keratitis) in either eye |
Ocular trauma ≤6 months before the study |
Ocular infection/inflammation ≤3 months before the study |
Clinically significant or progressive retinal disease (e.g., retinal degeneration, diabetic retinopathy, retinal detachment) in either eye |
BCVA score worse than 55 ETDRS letters in either eye |
Ocular pathology in either eye that may prohibit the administration of an α-adrenergic agonist or a topical CAI |
Intraocular surgery ≤6 months before the study |
Ocular laser surgery ≤3 months before the study |
Any abnormality preventing reliable applanation tonometry |
Severe illness or other condition that would make the patient unsuitable for the study, according to the investigator |
Active or prior severe, unstable, or uncontrolled cardiovascular, cerebrovascular, hepatic, or renal disease that would prevent safe administration of topical α-adrenergic agonists or carbonic anhydrase inhibitors, according to the investigator |
Use of high-dose (>1 g daily) salicylate therapy ≤4 weeks before first eligibility visit |
Current or anticipated treatment with any psychotropic drugs that augment adrenergic response (e.g., desipramine, amitriptyline) |
Therapy with another investigational agent ≤30 days before the screening visit |
Hypersensitivity to α-adrenergic agonist drugs (e.g., brimonidine), topical or oral CAIs (brinzolamide), sulfonamide derivatives, or any components of the study medications |
<30-day stable dosing regimen before the screening visit of any long-term medication or substance that may affect IOP (e.g., β-blockers) |
Concurrent use of a monoamine oxidase inhibitor, any additional systemic or topical ocular hypotensive medications, or glucocorticoid medications |
Outcomes
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Mean diurnal IOP change from baseline to week 2, week 6, and month 6;
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Mean IOP at each study visit and time point (i.e., week 2, week 6, month 3, and month 6 at 9 a.m. and 11 a.m.);
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Mean IOP change from baseline at each study visit and time point;
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Mean IOP percentage change from baseline at each study visit and time point;
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Percentage of patients with IOP <18 mmHg at each study visit and time point.
Statistical Analyses
Results
Patients
Characteristics | BBFC (n = 420) | BRINZ + BRIM (n = 411) |
---|---|---|
Mean ± SD age, years | 63 ± 12 | 63 ± 12 |
Age ≥65 years, n (%) | 210 (50.0) | 215 (52.3) |
Sex, n (%) | ||
Men | 187 (44.5) | 178 (43.3) |
Women | 233 (55.5) | 233 (56.7) |
Race, n (%) | ||
White | 269 (64.0) | 268 (65.2) |
Asian | 68 (16.2) | 57 (13.9) |
Other | 65 (15.5) | 66 (16.1) |
Black or African American | 16 (3.8) | 19 (4.6) |
Multiracial | 2 (0.5) | 1 (0.2) |
Diagnosis, n (%) | ||
Ocular hypertension | 90 (21.4) | 89 (21.7) |
Open-angle glaucoma | 321 (76.4) | 310 (75.4) |
Open-angle glaucoma with pigment dispersion | 4 (1.0) | 5 (1.2) |
Open-angle glaucoma with pseudoexfoliation | 5 (1.2) | 7 (1.7) |
Mean ± SE baseline IOP, mmHg | ||
9 a.m. | 27.0 ± 0.13 | 27.0 ± 0.13 |
11 a.m. | 25.8 ± 0.14 | 25.9 ± 0.15 |
Diurnal IOP (9 a.m., 11 a.m.) | 26.4 ± 0.13 | 26.5 ± 0.13 |
Mean ± SD cornea thickness, mm | 0.55 ± 0.04 | 0.55 ± 0.04 |
Efficacy
Time point | BBFC | BRINZ + BRIM | ||||||
---|---|---|---|---|---|---|---|---|
n
| Mean ± SE | IOP change from baseline, mmHg |
n
| Mean ± SE | IOP change from baseline, mmHg | |||
Mean ± SE | Percentage ± SE | Mean ± SE | Percentage ± SE | |||||
Week 2 | ||||||||
9 a.m. | 394 | 19.4 ± 0.18 | –7.6 ± 0.16 | –28.3 ± 0.58 | 384 | 19.1 ± 0.18 | –7.9 ± 0.17 | –29.1 ± 0.59 |
11 a.m. | 392 | 16.2 ± 0.16 | –9.6 ± 0.16 | –37.0 ± 0.54 | 383 | 16.3 ± 0.15 | –9.6 ± 0.16 | –36.8 ± 0.55 |
Month 3 | ||||||||
9 a.m. | 384 | 19.2 ± 0.19 | –7.7 ± 0.17 | –28.6 ± 0.58 | 373 | 19.3 ± 0.17 | –7.8 ± 0.16 | –28.6 ± 0.57 |
11 a.m. | 380 | 16.0 ± 0.16 | –9.7 ± 0.16 | –37.6 ± 0.55 | 363 | 16.2 ± 0.16 | –9.7 ± 0.17 | –37.4 ± 0.56 |
Month 6 | ||||||||
9 a.m. | 345 | 19.7 ± 0.20 | –7.3 ± 0.18 | –27.0 ± 0.65 | 330 | 19.5 ± 0.21 | –7.7 ± 0.19 | –28.2 ± 0.66 |
11 a.m. | 344 | 16.4 ± 0.17 | –9.3 ± 0.17 | –35.9 ± 0.60 | 328 | 16.5 ± 0.19 | –9.4 ± 0.18 | –36.1 ± 0.63 |
Safety
Parametera, n (%) | BBFC (n = 452) | BRINZ + BRIM (n = 436) |
---|---|---|
Deaths | 0 (0.0) | 1 (0.2) |
Non-fatal SAEs | 11 (2.4) | 7 (1.6) |
Discontinuation because of a treatment-related non-serious AE | 45 (10.0) | 51 (11.7) |
Patients with ADRs | 106 (23.5) | 117 (26.8) |
ADRs (≥1% incidence) | ||
Hyperemia | 25 (5.5) | 30 (6.9) |
Ocular | 16 (3.5) | 17 (3.9) |
Conjunctival | 9 (2.0) | 13 (3.0) |
Allergic conjunctivitis | 14 (3.1) | 9 (2.1) |
Eye irritation | 12 (2.7) | 7 (1.6) |
Dry mouth | 11 (2.4) | 14 (3.2) |
Dysgeusia | 11 (2.4) | 16 (3.7) |
Blurred vision | 9 (2.0) | 13 (3.0) |
Somnolence | 7 (1.5) | 15 (3.4) |
Eye pain | 7 (1.5) | 8 (1.8) |
Eye pruritus | 7 (1.5) | 8 (1.8) |
Eye allergy | 5 (1.1) | 6 (1.4) |
Conjunctivitis | 5 (1.1) | 5 (1.1) |
Blepharitis | 5 (1.1) | 4 (0.9) |
Increased lacrimation | 5 (1.1) | 4 (0.9) |
Punctate keratitis | 4 (0.9) | 6 (1.4) |
Foreign body sensation in eyes | 1 (0.2) | 5 (1.1) |