Open-Angle Glaucoma, Ocular Hypertension
Conditions
Keywords
Open-Angle Glaucoma, Ocular Hypertension, Brinzolamide, Brimonidine, Intraocular pressure
Brief summary
The purpose of this study was to evaluate the safety and efficacy of a new ophthalmic suspension (Brinz/Brim) in lowering intraocular pressure (IOP) relative to its individual active components in subjects with open-angle glaucoma and/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 the treatment phase, which included 4 on-therapy visits conducted at Week 2, Week 6, Month 3, and Month 6. A washout period based on previous ocular medication preceded Eligibility Visit 1. Subjects who met all inclusion/exclusion criteria at both eligibility visits were randomized to 1 of 3 study drug groups. The study was designed to evaluate the efficacy and safety of Brinzolamide/Brimonidine over a 3-month period, with an additional 3 months of study drug exposure intended to provide further safety data.
Interventions
Sponsors
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Sign Informed Consent document. * Diagnosis of open-angle glaucoma or ocular hypertension, with mean intraocular pressure within protocol-specified range at eligibility visit/s. * Other protocol-specified inclusion criteria may apply.
Exclusion criteria
* Females of childbearing potential if pregnant, lactating, or not using highly effective birth control measures. * Any form of glaucoma other than open-angle glaucoma. * Severe central vision loss in either eye. * 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 such as retinal degeneration, diabetic retinopathy, or retinal detachment. * Best-corrected visual acuity score worse than 55 letters using the Early Treatment Diabetic Retinopathy Study chart. * Other ocular pathology (including severe dry eye) that may, in the opinion of the Investigator, preclude the administration of study product. * Ocular surgery within the preceding 6 months. * Ocular laser surgery within the preceding 3 months. * Any abnormality preventing reliable applanation tonometry. * Any other conditions, including severe illness, which could make the subject, in the opinion of the Investigator, unsuitable for the study. * Other protocol-specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3 | Month 3 | The study drug was instilled at 8 AM and 3 PM (approximately 15 minutes after conducting the IOP measurements). Intraocular pressure was measured by Goldmann applanation tonometry. One eye from each patient 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 and enrolled from 64 investigational centers in the United States.
Pre-assignment details
Of the 1062 enrolled, 372 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 (690), as treated.
Participants by arm
| Arm | Count |
|---|---|
| Brinz/Brim Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled in each eye 3 times a day for 3 months | 221 |
| Brinzolamide Brinzolamide ophthalmic suspension, 1%, 1 drop instilled in each eye 3 times a day for 3 months | 234 |
| Brimonidine Brimonidine tartrate ophthalmic solution, 0.2%, 1 drop instilled in each eye 3 times a day for 3 months | 235 |
| Total | 690 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 42 | 10 | 38 |
| Overall Study | Inadequate Control of IOP | 7 | 9 | 17 |
| Overall Study | Noncompliance | 1 | 0 | 0 |
| Overall Study | Patient Decision Unrelated to AE | 6 | 5 | 2 |
| Overall Study | Patient Did Not Meet Entrance Criteria | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 3 | 0 |
Baseline characteristics
| Characteristic | Brinz/Brim | Brinzolamide | Brimonidine | Total |
|---|---|---|---|---|
| Age, Customized 18 to 64 years | 99 participants | 113 participants | 115 participants | 327 participants |
| Age, Customized ≥65 years | 122 participants | 121 participants | 120 participants | 363 participants |
| Region of Enrollment United States | 221 participants | 234 participants | 235 participants | 690 participants |
| Sex: Female, Male Female | 119 Participants | 136 Participants | 132 Participants | 387 Participants |
| Sex: Female, Male Male | 102 Participants | 98 Participants | 103 Participants | 303 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 | 53 / 221 | 35 / 234 | 27 / 235 |
| serious Total, serious adverse events | 7 / 221 | 7 / 234 | 7 / 235 |
Outcome results
Primary
Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3
The study drug was instilled at 8 AM and 3 PM (approximately 15 minutes after conducting the IOP measurements). Intraocular pressure was measured by Goldmann applanation tonometry. One eye from each patient 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: Month 3
Population: Intent-to-Treat (ITT): All subjects who received study medication and completed at least 1 scheduled on-therapy study visit. Observed case analysis of the ITT dataset, per randomized treatment assignment.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brinz/Brim | Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3 | 8 AM (before study drug instillation) | 21.1 millimeters mercury (mm HG) | Standard Error 0.3 |
| Brinz/Brim | Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3 | + 2 hours relative to 8 AM dosing | 18.0 millimeters mercury (mm HG) | Standard Error 0.3 |
| Brinz/Brim | Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3 | + 7 hours relative to 8 AM dosing | 19.5 millimeters mercury (mm HG) | Standard Error 0.3 |
| Brinz/Brim | Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3 | + 9 hours relative to 8 AM dosing | 17.2 millimeters mercury (mm HG) | Standard Error 0.3 |
| Brinzolamide | Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3 | + 9 hours relative to 8 AM dosing | 20.4 millimeters mercury (mm HG) | Standard Error 0.29 |
| Brinzolamide | Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3 | 8 AM (before study drug instillation) | 22.0 millimeters mercury (mm HG) | Standard Error 0.29 |
| Brinzolamide | Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3 | + 7 hours relative to 8 AM dosing | 20.7 millimeters mercury (mm HG) | Standard Error 0.29 |
| Brinzolamide | Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3 | + 2 hours relative to 8 AM dosing | 20.8 millimeters mercury (mm HG) | Standard Error 0.29 |
| Brimonidine | Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3 | + 9 hours relative to 8 AM dosing | 18.9 millimeters mercury (mm HG) | Standard Error 0.3 |
| Brimonidine | Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3 | + 2 hours relative to 8 AM dosing | 19.9 millimeters mercury (mm HG) | Standard Error 0.3 |
| Brimonidine | Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3 | + 7 hours relative to 8 AM dosing | 21.5 millimeters mercury (mm HG) | Standard Error 0.3 |
| Brimonidine | Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3 | 8 AM (before study drug instillation) | 23.2 millimeters mercury (mm HG) | Standard Error 0.3 |