Open-Angle Glaucoma, Ocular Hypertension
Conditions
Brief summary
The purpose of this study is to evaluate the additive intraocular pressure (IOP) lowering effect of brinzolamide 1%/brimonidine 0.2% (dosed twice per day (BID)) when added to a prostaglandin analogue (PGA) in subjects with open-angle glaucoma or ocular hypertension.
Detailed description
This study consisted of 2 sequential phases: Screening/Eligibility Phase, followed by a Masked Treatment Phase (Phase II). Subjects were assigned into one of 3 PGA therapy groups for the duration of the study, based upon commercial availability.
Interventions
DRUGBrinz/brim vehicle
Inactive ingredients used as a placebo for masking purposes
Sponsors
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of either open-angle glaucoma or ocular hypertension; * Must sign an informed consent form; * Mean IOP measurements at both the Eligibility 1 and 2 visits, in at least 1 eye (the same eye\[s\]) ≥ 19 and \< 32 mmHg at 09:00. * Willing and able to attend all study visits; * Other protocol-specified inclusion criteria may apply.
Exclusion criteria
* Women of childbearing potential who are pregnant, breast-feeding, intend to become pregnant during the study, or not using adequate birth control methods to prevent pregnancy throughout the study; * Any form of glaucoma other than open-angle glaucoma or ocular hypertension; * Ocular disease, trauma, infection, inflammation, pathology, or surgery as specified in the protocol; * Any other conditions including severe illness which would make the subject, in the opinion of the Investigator, unsuitable for the study; * Other protocol-specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline (on PGA) in Diurnal IOP (Mean of 09:00 and 11:00 Time Points) at Week 6 | Baseline, Week 6 | IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry and averaged over the 09:00 AM and 11:00 AM time points. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percentage Change From Baseline in Diurnal IOP at Week 6 | Baseline, Week 6 | IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry and averaged over the 09:00 AM and 11:00 AM time points. A more negative percent change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis. |
| Mean Change From Baseline in IOP at 11:00 at Week 6 | Baseline, Week 6 | IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 11:00 AM. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis. |
| Mean Diurnal IOP at Week 6 | Week 6 | IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry and averaged over the 09:00 AM and 11:00 AM time points. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye (study eye) contributed to the analysis. |
| Mean Change From Baseline in IOP at 09:00 at Week 6 | Baseline, Week 6 | IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 09:00 AM. Baseline is defined as the average of the 9:00 hour values at both Eligibility visits. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis. |
| Mean Percentage Change From Baseline at 09:00 at Week 6 | Baseline, Week 6 | IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 9:00 AM. Baseline is defined as the average of the 9:00 hour values at both Eligibility visits.A more negative percent change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis. |
| Mean Percentage Change From Baseline in IOP at 11:00 at Week 6 | Baseline, Week 6 | IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 11:00 AM. A more negative percent change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 37 sites located in Argentina (3), Australia (4), Canada (12), Chile (3), France (1), Germany (3), Greece (2), Israel (3), Spain (3), and United Kingdom (3).
Pre-assignment details
Of the 290 subjects enrolled in the study, 102 were exited during the Screening/Eligibility period. This reporting group includes all randomized subjects. One randomized subject did not receive investigational product and is excluded from the Full Analysis Set and the Safety Analysis Set.
Participants by arm
| Arm | Count |
|---|---|
| SIMBRINZA + PGA Brinzolamide 1%/brimonidine 0.2% tartrate ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days | 95 |
| Vehicle + PGA Brinz/brim vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00) plus designated prostaglandin analogue, 1 drop instilled in each eye once per day in the evening for 42 days | 92 |
| Total | 187 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 9 | 3 |
| Overall Study | Other - Reason not specified | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | SIMBRINZA + PGA | Vehicle + PGA | Total |
|---|---|---|---|
| Age, Continuous | 66.5 years STANDARD_DEVIATION 10.7 | 67.9 years STANDARD_DEVIATION 11.65 | 67.2 years STANDARD_DEVIATION 11.17 |
| Baseline Diurnal IOP | 22.8 millimeters mercury (mmHg) STANDARD_DEVIATION 2.39 | 22.9 millimeters mercury (mmHg) STANDARD_DEVIATION 2.32 | 22.8 millimeters mercury (mmHg) STANDARD_DEVIATION 2.35 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 29 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 72 Participants | 62 Participants | 134 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Europe, Australia | 45 Participants | 44 Participants | 89 Participants |
| Region of Enrollment Latin America, Canada | 50 Participants | 48 Participants | 98 Participants |
| Sex: Female, Male Female | 55 Participants | 43 Participants | 98 Participants |
| Sex: Female, Male Male | 40 Participants | 49 Participants | 89 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 95 | 0 / 92 |
| other Total, other adverse events | 10 / 95 | 1 / 92 |
| serious Total, serious adverse events | 1 / 95 | 0 / 92 |
Outcome results
Primary
Mean Change From Baseline (on PGA) in Diurnal IOP (Mean of 09:00 and 11:00 Time Points) at Week 6
IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry and averaged over the 09:00 AM and 11:00 AM time points. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
Time frame: Baseline, Week 6
Population: FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SIMBRINZA + PGA | Mean Change From Baseline (on PGA) in Diurnal IOP (Mean of 09:00 and 11:00 Time Points) at Week 6 | -5.6 mmHg | Standard Deviation 2.72 |
| Vehicle + PGA | Mean Change From Baseline (on PGA) in Diurnal IOP (Mean of 09:00 and 11:00 Time Points) at Week 6 | -2.1 mmHg | Standard Deviation 2.61 |
p-value: <0.001Mixed Models Analysis
Secondary
Mean Change From Baseline in IOP at 09:00 at Week 6
IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 09:00 AM. Baseline is defined as the average of the 9:00 hour values at both Eligibility visits. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
Time frame: Baseline, Week 6
Population: FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SIMBRINZA + PGA | Mean Change From Baseline in IOP at 09:00 at Week 6 | Baseline | 23.4 mmHg | Standard Deviation 2.4 |
| SIMBRINZA + PGA | Mean Change From Baseline in IOP at 09:00 at Week 6 | Change from baseline | -4.9 mmHg | Standard Deviation 3.06 |
| Vehicle + PGA | Mean Change From Baseline in IOP at 09:00 at Week 6 | Baseline | 23.4 mmHg | Standard Deviation 2.22 |
| Vehicle + PGA | Mean Change From Baseline in IOP at 09:00 at Week 6 | Change from baseline | -2.5 mmHg | Standard Deviation 2.87 |
p-value: <0.001Mixed Models Analysis
Secondary
Mean Change From Baseline in IOP at 11:00 at Week 6
IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 11:00 AM. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
Time frame: Baseline, Week 6
Population: FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SIMBRINZA + PGA | Mean Change From Baseline in IOP at 11:00 at Week 6 | Baseline | 22.4 mmHg | Standard Deviation 2.7 |
| SIMBRINZA + PGA | Mean Change From Baseline in IOP at 11:00 at Week 6 | Change from baseline | -7.0 mmHg | Standard Deviation 3.19 |
| Vehicle + PGA | Mean Change From Baseline in IOP at 11:00 at Week 6 | Baseline | 22.6 mmHg | Standard Deviation 2.69 |
| Vehicle + PGA | Mean Change From Baseline in IOP at 11:00 at Week 6 | Change from baseline | -2.4 mmHg | Standard Deviation 2.78 |
p-value: <0.001Mixed Models Analysis
Secondary
Mean Diurnal IOP at Week 6
IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry and averaged over the 09:00 AM and 11:00 AM time points. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye (study eye) contributed to the analysis.
Time frame: Week 6
Population: FAS with data available
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SIMBRINZA + PGA | Mean Diurnal IOP at Week 6 | 17.2 mmHg | Standard Deviation 3.49 |
| Vehicle + PGA | Mean Diurnal IOP at Week 6 | 20.9 mmHg | Standard Deviation 3.59 |
p-value: <0.001Mixed Models Analysis
Secondary
Mean Percentage Change From Baseline at 09:00 at Week 6
IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 9:00 AM. Baseline is defined as the average of the 9:00 hour values at both Eligibility visits.A more negative percent change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
Time frame: Baseline, Week 6
Population: FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SIMBRINZA + PGA | Mean Percentage Change From Baseline at 09:00 at Week 6 | -21.0 percent change | Standard Deviation 13.36 |
| Vehicle + PGA | Mean Percentage Change From Baseline at 09:00 at Week 6 | -10.9 percent change | Standard Deviation 11.83 |
p-value: <0.001Mixed Models Analysis
Secondary
Mean Percentage Change From Baseline in Diurnal IOP at Week 6
IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry and averaged over the 09:00 AM and 11:00 AM time points. A more negative percent change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
Time frame: Baseline, Week 6
Population: FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SIMBRINZA + PGA | Mean Percentage Change From Baseline in Diurnal IOP at Week 6 | -24.7 percent change | Standard Deviation 12.17 |
| Vehicle + PGA | Mean Percentage Change From Baseline in Diurnal IOP at Week 6 | -9.5 percent change | Standard Deviation 10.92 |
p-value: <0.001Mixed Models Analysis
Secondary
Mean Percentage Change From Baseline in IOP at 11:00 at Week 6
IOP (fluid pressure inside the eye) was measured using Goldmann applanation tonometry at 11:00 AM. A more negative percent change from baseline indicates a greater improvement, i.e., a reduction of IOP. One eye (study eye) contributed to the analysis.
Time frame: Baseline, Week 6
Population: FAS. Only subjects with a value at both baseline and time point are included in the calculation of change.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SIMBRINZA + PGA | Mean Percentage Change From Baseline in IOP at 11:00 at Week 6 | -31.3 percent change | Standard Deviation 14.81 |
| Vehicle + PGA | Mean Percentage Change From Baseline in IOP at 11:00 at Week 6 | -10.8 percent change | Standard Deviation 11.86 |
p-value: <0.001Mixed Models Analysis