Open-Angle Glaucoma, Ocular Hypertension
Conditions
Keywords
AOG, OHT, Open-Angle Glaucoma, Ocular Hypertension
Brief summary
The purpose of this study was to evaluate the efficacy and safety of a fixed combination of Brinzolamide/Brimonidine in lowering intraocular pressure (IOP) relative to each of its individual active components in patients with open-angle glaucoma and/or ocular hypertension.
Detailed description
This study consisted of 6 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 3 on-therapy visits conducted at Week 2, Week 6, and Month 3. A washout period based on previous ocular medication preceded Eligibility Visit 1. Patients who met all inclusion/exclusion criteria at both eligibility visits were randomized (1:1:1) to receive treatment with 1 of 3 study drugs for 3 months. Study drug instillation began the morning after the second eligibility visit.
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 patient, in the opinion of the Investigator, unsuitable for the study. * Other protocol-specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h) | Month 3 | At the Month 3 (Exit) visit, the 8 am IOP measurement was taken before instillation of study drug. The study drug was instilled approximately 15 minutes after the 8 am measurement. An additional dose was given at 3 pm. 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 from 68 study centers in the US.
Pre-assignment details
Of the 1001 enrolled, 341 subjects did not qualify for treatment and were exited without exposure to product. The 660 subjects eligible for treatment were randomized (1:1:1) to study drug. This reporting group includes all randomized subjects, as treated.
Participants by arm
| Arm | Count |
|---|---|
| Brinzolamide/Brimonidine Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months | 214 |
| Brinzolamide Brinzolamide ophthalmic suspension, 1%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months | 226 |
| Brimonidine Brimonidine tartrate ophthalmic solution, 0.2%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months | 220 |
| Total | 660 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 21 | 7 | 16 |
| Overall Study | Inadequate Control of IOP | 1 | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 |
| Overall Study | Noncompliance | 1 | 0 | 0 |
| Overall Study | Patient Decision Unrelated to AE | 2 | 3 | 7 |
| Overall Study | Protocol Violation | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Brinzolamide/Brimonidine | Brinzolamide | Brimonidine | Total |
|---|---|---|---|---|
| Age, Customized 18 to 64 years | 107 participants | 101 participants | 117 participants | 325 participants |
| Age, Customized ≥65 years | 107 participants | 125 participants | 103 participants | 335 participants |
| Sex: Female, Male Female | 140 Participants | 128 Participants | 135 Participants | 403 Participants |
| Sex: Female, Male Male | 74 Participants | 98 Participants | 85 Participants | 257 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 | 20 / 214 | 26 / 226 | 1 / 220 |
| serious Total, serious adverse events | 2 / 214 | 6 / 226 | 2 / 220 |
Outcome results
Primary
Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h)
At the Month 3 (Exit) visit, the 8 am IOP measurement was taken before instillation of study drug. The study drug was instilled approximately 15 minutes after the 8 am measurement. An additional dose was given at 3 pm. 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 patients 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 |
|---|---|---|---|---|
| Brinzolamide/Brimonidine | Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h) | 8 am (before study drug instillation) | 20.5 millimeters mercury (mm Hg) | Standard Error 0.29 |
| Brinzolamide/Brimonidine | Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h) | +2 hrs relative to 8 am dosing | 17.2 millimeters mercury (mm Hg) | Standard Error 0.29 |
| Brinzolamide/Brimonidine | Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h) | +7 hrs relative to 8 am dosing | 18.7 millimeters mercury (mm Hg) | Standard Error 0.29 |
| Brinzolamide/Brimonidine | Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h) | +9 hrs relative to 8 am dosing | 17.0 millimeters mercury (mm Hg) | Standard Error 0.29 |
| Brinzolamide | Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h) | +9 hrs relative to 8 am dosing | 20.0 millimeters mercury (mm Hg) | Standard Error 0.28 |
| Brinzolamide | Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h) | 8 am (before study drug instillation) | 21.6 millimeters mercury (mm Hg) | Standard Error 0.28 |
| Brinzolamide | Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h) | +7 hrs relative to 8 am dosing | 20.4 millimeters mercury (mm Hg) | Standard Error 0.28 |
| Brinzolamide | Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h) | +2 hrs relative to 8 am dosing | 20.4 millimeters mercury (mm Hg) | Standard Error 0.28 |
| Brimonidine | Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h) | +9 hrs relative to 8 am dosing | 18.8 millimeters mercury (mm Hg) | Standard Error 0.29 |
| Brimonidine | Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h) | +2 hrs relative to 8 am dosing | 19.7 millimeters mercury (mm Hg) | Standard Error 0.29 |
| Brimonidine | Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h) | +7 hrs relative to 8 am dosing | 21.3 millimeters mercury (mm Hg) | Standard Error 0.29 |
| Brimonidine | Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h) | 8 am (before study drug instillation) | 23.3 millimeters mercury (mm Hg) | Standard Error 0.29 |