Open-Angle Glaucoma, Ocular Hypertension
Conditions
Keywords
Open-Angle glaucoma, Ocular Hypertension, OAG, OHT
Brief summary
The purpose of this study was to evaluate the safety and efficacy of Brinzolamide/Brimonidine in lowering intraocular pressure (IOP) relative to each of its individual active components in patients with open-angle glaucoma or ocular hypertension.
Detailed description
This study consisted of 7 visits conducted during 2 sequential phases: the screening/eligibility phase, which included a screening visit and 2 eligibility visits, and a treatment phase, which included 4 on-therapy visits conducted at Week 2, Week 6, Month 3, and Month 6 (or early exit). Following washout of any IOP-lowering medication, subjects who met all inclusion/exclusion criteria at both eligibility visits and who had IOP measurements within the specified range during this period were randomized to 1 of 3 study drug groups: Brinz/Brim, Brinz, or Brim.
Interventions
Sponsors
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with open angle glaucoma or ocular hypertension, and, in the opinion of the Investigator, are insufficiently controlled on monotherapy or are currently on multiple IOP-lowering medications. * Meet qualifying IOP entry criteria. * Able to understand and sign an informed consent form. * Other protocol-specified inclusion criteria may apply.
Exclusion criteria
* Women of childbearing potential if pregnant, test positive for pregnancy at Screening Visit, breastfeeding, or not in agreement to use adequate birth control methods to prevent pregnancy throughout the study. * Severe central visual field loss. * Best corrected visual acuity (BCVA) score worse than 55 ETDRS letters (20/80 Snellen equivalent). * Chronic, recurrent or severe inflammatory eye disease. * Ocular trauma within the preceding 6 months. * Ocular infection or ocular inflammation within the preceding 3 months. * Clinically significant or progressive retinal disease. * Other ocular pathology. * Intraocular surgery within the 6 months prior to entry. * Ocular laser surgery within the 3 months prior to entry. * Any abnormality preventing reliable applanation tonometry. * Any other conditions, including severe illness, which would make the subject, in the opinion of the Investigator, unsuitable for the study. * Recent use of high-dose (\>1 gram daily) salicylate therapy. * Recent, current, or anticipated treatment with any medication that augments adrenergic responses, or precludes use of an alpha-adrenergic agonist. * Concurrent use of glucocorticoid medications administered by any route. * Other protocol-specified exclusion crtieria may apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Diurnal IOP Change From Baseline at Month 3 | Baseline (Day 1), Month 3 | Mean Diurnal IOP Change from Baseline at Month 3 (ie, the subject IOP change from baseline averaged over the 9 AM, + 2 h, and + 7 h time points at Month 3) was measured by Goldmann applanation tonometry. The study drug was instilled approximately 15 minutes after conducting the 9AM IOP measurement. One eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). |
Participant flow
Recruitment details
Subjects were recruited from 63 investigational centers in the Asia-Pacific region, the European Union, Latin America and Caribbean nations, and the United States.
Pre-assignment details
Of the 771 enrolled, 211 subjects did not meet inclusion/exclusion criteria and were exited from the study as screen failures prior to randomization. This reporting group includes all randomized subjects (560).
Participants by arm
| Arm | Count |
|---|---|
| Brinz/Brim Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled in each eye 2 times a day for 6 months | 193 |
| Brinz Brinzolamide 1% ophthalmic suspension, 1 drop instilled in each eye 2 times a day for 6 months | 192 |
| Brim Brimonidine tartrate 0.2% ophthalmic solution, 1 drop instilled in each eye 2 times a day for 6 months | 175 |
| Total | 560 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 23 | 1 | 15 |
| Overall Study | Inadequate Control of IOP | 5 | 7 | 10 |
| Overall Study | Lost to Follow-up | 0 | 4 | 1 |
| Overall Study | Other | 4 | 1 | 2 |
| Overall Study | Patient's Decision Unrelated to AE | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | Brinz/Brim | Brinz | Brim | Total |
|---|---|---|---|---|
| Age, Customized <65 years | 91 participants | 87 participants | 79 participants | 257 participants |
| Age, Customized ≥65 years | 102 participants | 105 participants | 96 participants | 303 participants |
| Sex: Female, Male Female | 106 Participants | 102 Participants | 102 Participants | 310 Participants |
| Sex: Female, Male Male | 87 Participants | 90 Participants | 73 Participants | 250 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 44 / 193 | 12 / 192 | 18 / 175 |
| serious Total, serious adverse events | 5 / 193 | 2 / 192 | 3 / 175 |
Outcome results
Primary
Mean Diurnal IOP Change From Baseline at Month 3
Mean Diurnal IOP Change from Baseline at Month 3 (ie, the subject IOP change from baseline averaged over the 9 AM, + 2 h, and + 7 h time points at Month 3) was measured by Goldmann applanation tonometry. The study drug was instilled approximately 15 minutes after conducting the 9AM IOP measurement. One eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage).
Time frame: Baseline (Day 1), Month 3
Population: The intent-to-treat (ITT) analysis set included all subjects who received study drug and completed at least 1 scheduled on-therapy study visit.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Brinz/Brim | Mean Diurnal IOP Change From Baseline at Month 3 | -7.9 millimeters of mercury (mmHg) | Standard Error 0.22 |
| Brinz | Mean Diurnal IOP Change From Baseline at Month 3 | -6.5 millimeters of mercury (mmHg) | Standard Error 0.23 |
| Brim | Mean Diurnal IOP Change From Baseline at Month 3 | -6.4 millimeters of mercury (mmHg) | Standard Error 0.24 |