Ocular Hypertension, Open-Angle Glaucoma
Conditions
Keywords
OAG, OHT
Brief summary
The purpose of this study is to compare the fixed combination (BID) \[Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL eyes drops, suspension\] to the unfixed combination (BID) \[Brinzolamide 10 mg/mL eye drops, suspension plus Brimonidine 2 mg/mL eyes drops, solution\] with respect to intraocular pressure (IOP)-lowering efficacy.
Detailed description
This study is divided into 2 phases conducted in sequence for a total of 6 visits: Phase I (Screening/Eligibility) which includes a Screening Visit, followed by 2 Eligibility Visits (E1 and E2) and Phase II (Treatment/Follow-up) which includes 3 visits at Week 2, Week 6, and Month 3. Following washout of any IOP-lowering medication, subjects who meet all inclusion/exclusion criteria at both Eligibility visits and had IOP measurements within the specified range during this period will be randomized to Phase II.
Interventions
DRUGBrinzolamide 10 mg/mL / Brimonidine 2 mg/mL fixed combination eye drops, suspension
DRUGBrinzolamide 10 mg/mL eye drops, suspension
DRUGBrimonidine 2 mg/mL eye drops, solution
DRUGVehicle
Inactive ingredients used as a placebo for masking purposes
Sponsors
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 95 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of open-angle glaucoma or ocular hypertension insufficiently controlled on monotherapy or currently on multiple IOP-lowering medications; * Mean IOP measurements within guidelines specified in the protocol. Must not be \> 36 mmHg at any time point; * Able to understand and sign an informed consent form; * Other protocol-specified inclusion criteria may apply.
Exclusion criteria
* Women of childbearing potential who are pregnant, test positive for pregnancy, intend to become pregnant during the study period, breast-feeding, or not in agreement to use adequate birth control methods throughout the study; * Severe central visual field loss in either eye; * Unable to safely discontinue all IOP-lowering ocular medication(s) for a minimum of 5 (± 1) to 28 (± 1) days prior to E1 Visit; * Chronic, recurrent or severe inflammatory eye disease; * Ocular trauma within the past 6 months; * Ocular infection or ocular inflammation within the past 3 months; * Clinically significant or progressive retinal disease such as retinal degeneration, diabetic retinopathy, or retinal detachment; * Best-corrected visual acuity (BCVA) score worse than 55 ETDRS letters (equivalent to approximately 0.60 logMAR, 20/80 Snellen, or 0.25 decimal); * Other ocular pathology (including severe dry eye) that may preclude the administration of α-adrenergic agonist and/or topical carbonic anhydrase inhibitor (CAI); * Intraocular surgery within the past 6 months; * Ocular laser surgery within the past 3 months; * Any abnormality preventing reliable applanation tonometry; * Any conditions including severe illness which would make the Subject, in the opinion of the Investigator, unsuitable for the study; * History of active, severe, unstable or uncontrolled cardiovascular, cerebrovascular, hepatic, or renal disease that would preclude safe administration of a topical α-adrenergic agonist or CAI; * Recent (within 4 weeks of the E1 Visit) use of high-dose (\> 1 g daily) salicylate therapy; * Current or anticipated treatment with any psychotropic drugs that augment adrenergic response (eg, desipramine, amitriptyline); * Concurrent use of monoamine oxidase inhibitors (MAOI); * Concurrent use of glucocorticoids administered by any route; * Therapy with another investigational agent within 30 days prior to the Screening Visit; * Hypersensitivity to α-adrenergic agonist drugs, topical or oral CAIs, sulfonamide derivatives, or to any component of the study medications; * Less than 30 days stable dosing regimen before the Screening Visit of any medications (excluding IOP-lowering treatments) or substances administered by any route and used on a chronic basis that may affect IOP, including but not limited to β-adrenergic blocking agents; * Use of any additional topical or systemic ocular hypotensive medication during the study; * Other protocol-specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Diurnal IOP Change From Baseline at Month 3 | Baseline (Day 0), Month 3 | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in mmHg. Diurnal IOP was defined as the average of the three timepoints measured: 9 AM, +2 Hrs and +7Hrs. Baseline was the average of the values for 2 eligibility visits. If one of the values was missing, the other non-missing value was taken as the baseline. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates greater improvement, ie, a reduction of IOP. Only one eye (study eye) contributed to the analysis. |
Participant flow
Recruitment details
Subjects were recruited from 26 study centers located in China (14), Russia (9), and Taiwan (3).
Pre-assignment details
Of the 493 enrolled, 64 subjects were exited as screen failures and another 50 discontinued prior to randomization. This reporting group includes all randomized subjects (379).
Participants by arm
| Arm | Count |
|---|---|
| Brinz/Brim Vehicle solution, 1 drop, followed by Brinzolamide 10 mg/mL / Brimonidine 2 mg/mL fixed combination eye drops, suspension, 1 drop, administered at least 5 minutes apart in the treated eye(s) twice daily (BID) for 3 months | 172 |
| Brinz+Brim Brimonidine 2 mg/mL eye drops, solution, 1 drop, followed by Brinzolamide 10 mg/mL eye drops, suspension, 1 drop, administered at least 5 minutes apart in the treated eye(s) BID for 3 months | 177 |
| Total | 349 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 7 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Physician Decision | 1 | 2 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 4 |
Baseline characteristics
| Characteristic | Brinz/Brim | Brinz+Brim | Total |
|---|---|---|---|
| Age, Continuous | 52.3 years STANDARD_DEVIATION 16.29 | 52.6 years STANDARD_DEVIATION 16.25 | 52.4 years STANDARD_DEVIATION 16.25 |
| Mean Diurnal Intraocular Pressure (IOP) | 24.62 mmHg STANDARD_DEVIATION 2.661 | 24.59 mmHg STANDARD_DEVIATION 2.66 | 24.61 mmHg STANDARD_DEVIATION 2.657 |
| Sex: Female, Male Female | 97 Participants | 98 Participants | 195 Participants |
| Sex: Female, Male Male | 75 Participants | 79 Participants | 154 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 188 | 0 / 191 |
| other Total, other adverse events | 12 / 188 | 13 / 191 |
| serious Total, serious adverse events | 4 / 188 | 4 / 191 |
Outcome results
Primary
Mean Diurnal IOP Change From Baseline at Month 3
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in mmHg. Diurnal IOP was defined as the average of the three timepoints measured: 9 AM, +2 Hrs and +7Hrs. Baseline was the average of the values for 2 eligibility visits. If one of the values was missing, the other non-missing value was taken as the baseline. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates greater improvement, ie, a reduction of IOP. Only one eye (study eye) contributed to the analysis.
Time frame: Baseline (Day 0), Month 3
Population: Per Protocol Analysis Set. Missing Month 3 data were imputed using a last observation carried forward method (LOCF).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Brinz/Brim | Mean Diurnal IOP Change From Baseline at Month 3 | -7.2 mmHg | Standard Error 0.34 |
| Brinz+Brim | Mean Diurnal IOP Change From Baseline at Month 3 | -7.3 mmHg | Standard Error 0.34 |