Ocular Hypertension, Open Angle Glaucoma
Conditions
Keywords
glaucoma, prostaglandin analogue, brinzolamide, brimonidine
Brief summary
The purpose of this study is to demonstrate the additive effect of brinzolamide 1%/brimonidine 0.2% (SIMBRINZA® suspension) in subjects with either open angle glaucoma or ocular hypertension who are currently on a prostaglandin analogue (PGA) monotherapy.
Detailed description
This study was divided into 2 sequential phases. The Screening/Eligibility Phase included one Screening Visit and two Eligibility Visits, during which subjects washed out of all other intraocular pressure (IOP)-lowering medications and dosed with TRAVATAN Z®, XALATAN®, or LUMIGAN®, 1 drop instilled in each eye once daily for 28 days. Subjects who met all inclusion/exclusion criteria were randomized at the second Eligibility Visit. The Treatment Phase consisted of two on-therapy visits (Week 2 and Week 6).
Interventions
DRUGVehicle
Inactive ingredients used as a placebo comparator
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 open angle glaucoma (including open-angle glaucoma with pseudoexfoliation or pigment dispersion) or ocular hypertension; * Mean intraocular pressure (IOP) measurements in at least 1 eye (study eye) of ≥ 21 mmHg and \<32 mmHg at 2 consecutive visits (Eligibility 1 and Eligibility 2); * Previously prescribed TRAVATAN Z® 0.004%, XALATAN® 0.005%, or LUMIGAN® 0.01% monotherapy for at least 28 days prior to the Screening Visit; * Able to understand and sign Informed Consent Document; * Other protocol-defined inclusion criteria may apply.
Exclusion criteria
* Women of childbearing potential who are pregnant, breastfeeding, or do not agree to use an adequate birth control method throughout the study; * Any form of glaucoma other than open angle glaucoma or ocular hypertension; * Severe central visual field loss; * Chronic, recurrent, or severe inflammatory eye disease; * Ocular trauma within the past 6 months; * Ocular infection or ocular inflammation within the past 3 months; * Best-corrected visual acuity score worse than approximately 20/80 Snellen; * Eye surgery within the past 6 months; * Any condition, including severe illness, which would make the subject unsuitable for the study in the opinion of the Investigator; * Use of any additional topical or systemic ocular hypertensive medication during the study; * Patients who, in the opinion of the Investigator, cannot discontinue all IOP-lowering ocular medication(s) per the appropriate washout schedule prior to Eligibility 1 Visit; * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Diurnal Intraocular Pressure (IOP) at Week 6 | Week 6 | Diurnal IOP was defined as the average of the four timepoints measured (8 AM, 10 AM, 3 PM, and 5 PM). IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in millimeters mercury (mmHg). One eye was chosen as the study eye and only data for the study eye were used for the analysis. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Diurnal IOP Change From Baseline to Week 6 | Baseline, Week 6 | Baseline IOP was defined as the average of the timepoint-matched IOP measurements at Eligibility 1 and Eligibility 2 Visits. Diurnal IOP change was defined as the average of the four changes from baseline (timepoints 8 AM, 10 AM, 3 PM, and 5 PM). IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in millimeters mercury (mmHg). One eye was chosen as the study eye and only data for the study eye were used for the analysis. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. |
| Mean Diurnal IOP Percentage Change From Baseline to Week 6 | Baseline, Week 6 | Baseline IOP was defined as the average of the timepoint-matched IOP measurements at Eligibility 1 and Eligibility 2 Visits. Diurnal IOP Percentage Change was defined as the average of the four percent changes from baseline (timepoints 8 AM, 10 AM, 3 PM, and 5 PM). IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in millimeters mercury (mmHg). One eye was chosen as the study eye and only data for the study eye were used for the analysis. A more negative percent change from baseline indicates a greater amount of improvement, i.e., a reduction of IOP. |
| Mean IOP at Week 6 for Each Time Point (8 AM, 10 AM, 3 PM, 5 PM) | Week 6 | IOP was assessed using Goldmann applanation tonometry and reported in mmHg. One eye was chosen as the study eye and only data for the study eye were used for the 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
Participants were recruited and enrolled from 30 investigative sites located in the US.
Pre-assignment details
Of the 282 enrolled, 93 participants were exited from the study as screen failures prior to randomization. This reporting group includes all randomized participants (189). Note: One subject randomized to SIMBRINZA® Suspension was not exposed to investigational product.
Participants by arm
| Arm | Count |
|---|---|
| SIMBRINZA 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks | 88 |
| Vehicle 1 drop in each eye 3 times a day (8 AM, 3 PM, 10 PM), with prostaglandin analogue, 1 drop in each eye at bedtime, for 6 weeks | 94 |
| Total | 182 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 1 |
| Overall Study | Lack of Efficacy | 0 | 1 |
| Overall Study | Withdrawal of subject prior to treatment | 1 | 1 |
Baseline characteristics
| Characteristic | SIMBRINZA | Vehicle | Total |
|---|---|---|---|
| Age, Continuous | 65.5 years STANDARD_DEVIATION 9.4 | 64.7 years STANDARD_DEVIATION 9.6 | 65.1 years STANDARD_DEVIATION 9.5 |
| Mean Diurnal Intraocular Pressure (IOP) at Baseline | 22.68 mmHg STANDARD_DEVIATION 2.123 | 22.39 mmHg STANDARD_DEVIATION 2.774 | 22.53 mmHg STANDARD_DEVIATION 2.478 |
| Sex: Female, Male Female | 53 Participants | 63 Participants | 116 Participants |
| Sex: Female, Male Male | 35 Participants | 31 Participants | 66 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 | 2 / 282 | 16 / 93 | 8 / 95 |
| serious Total, serious adverse events | 0 / 282 | 1 / 93 | 0 / 95 |
Outcome results
Primary
Mean Diurnal Intraocular Pressure (IOP) at Week 6
Diurnal IOP was defined as the average of the four timepoints measured (8 AM, 10 AM, 3 PM, and 5 PM). IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in millimeters mercury (mmHg). One eye was chosen as the study eye and only data for the study eye were used for the analysis. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage).
Time frame: Week 6
Population: This analysis population includes all subjects who received study medication and completed at least 1 scheduled on-therapy visit (intent-to-treat). Last observation carried forward (LOCF) was not utilized; therefore, results report subjects present at Week 6 with no imputation for missingness.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SIMBRINZA | Mean Diurnal Intraocular Pressure (IOP) at Week 6 | 17.01 mmHg | Standard Deviation 2.897 |
| Vehicle | Mean Diurnal Intraocular Pressure (IOP) at Week 6 | 20.37 mmHg | Standard Deviation 3.914 |
Secondary
Mean Diurnal IOP Change From Baseline to Week 6
Baseline IOP was defined as the average of the timepoint-matched IOP measurements at Eligibility 1 and Eligibility 2 Visits. Diurnal IOP change was defined as the average of the four changes from baseline (timepoints 8 AM, 10 AM, 3 PM, and 5 PM). IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in millimeters mercury (mmHg). One eye was chosen as the study eye and only data for the study eye were used for the analysis. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP.
Time frame: Baseline, Week 6
Population: This analysis population includes all subjects who received study medication and completed at least 1 scheduled on-therapy visit (intent-to-treat). Last observation carried forward (LOCF) was not utilized; therefore, results report subjects present at Week 6 with no imputation for missingness.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SIMBRINZA | Mean Diurnal IOP Change From Baseline to Week 6 | -5.69 mmHg | Standard Deviation 2.571 |
| Vehicle | Mean Diurnal IOP Change From Baseline to Week 6 | -1.99 mmHg | Standard Deviation 2.865 |
Secondary
Mean Diurnal IOP Percentage Change From Baseline to Week 6
Baseline IOP was defined as the average of the timepoint-matched IOP measurements at Eligibility 1 and Eligibility 2 Visits. Diurnal IOP Percentage Change was defined as the average of the four percent changes from baseline (timepoints 8 AM, 10 AM, 3 PM, and 5 PM). IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry and reported in millimeters mercury (mmHg). One eye was chosen as the study eye and only data for the study eye were used for the analysis. A more negative percent change from baseline indicates a greater amount of improvement, i.e., a reduction of IOP.
Time frame: Baseline, Week 6
Population: This analysis population includes all subjects who received study medication and completed at least 1 scheduled on-therapy visit (intent-to-treat). Last observation carried forward (LOCF) was not utilized; therefore, results report subjects present at Week 6 with no imputation for missingness.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SIMBRINZA | Mean Diurnal IOP Percentage Change From Baseline to Week 6 | -24.88 percent change | Standard Deviation 10.818 |
| Vehicle | Mean Diurnal IOP Percentage Change From Baseline to Week 6 | -8.50 percent change | Standard Deviation 12.396 |
Secondary
Mean IOP at Week 6 for Each Time Point (8 AM, 10 AM, 3 PM, 5 PM)
IOP was assessed using Goldmann applanation tonometry and reported in mmHg. One eye was chosen as the study eye and only data for the study eye were used for the analysis. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage).
Time frame: Week 6
Population: This analysis population includes all subjects who received study medication and completed at least 1 scheduled on-therapy visit (intent-to-treat). Last observation carried forward (LOCF) was not utilized; therefore, results report subjects present at Week 6 with no imputation for missingness.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SIMBRINZA | Mean IOP at Week 6 for Each Time Point (8 AM, 10 AM, 3 PM, 5 PM) | 8 AM | 19.4 mmHg | Standard Deviation 3.53 |
| SIMBRINZA | Mean IOP at Week 6 for Each Time Point (8 AM, 10 AM, 3 PM, 5 PM) | 10 AM | 15.8 mmHg | Standard Deviation 3.54 |
| SIMBRINZA | Mean IOP at Week 6 for Each Time Point (8 AM, 10 AM, 3 PM, 5 PM) | 3 PM | 17.2 mmHg | Standard Deviation 3.15 |
| SIMBRINZA | Mean IOP at Week 6 for Each Time Point (8 AM, 10 AM, 3 PM, 5 PM) | 5 PM | 15.6 mmHg | Standard Deviation 3.14 |
| Vehicle | Mean IOP at Week 6 for Each Time Point (8 AM, 10 AM, 3 PM, 5 PM) | 5 PM | 19.9 mmHg | Standard Deviation 4.41 |
| Vehicle | Mean IOP at Week 6 for Each Time Point (8 AM, 10 AM, 3 PM, 5 PM) | 8 AM | 21.4 mmHg | Standard Deviation 4.33 |
| Vehicle | Mean IOP at Week 6 for Each Time Point (8 AM, 10 AM, 3 PM, 5 PM) | 3 PM | 19.9 mmHg | Standard Deviation 4.28 |
| Vehicle | Mean IOP at Week 6 for Each Time Point (8 AM, 10 AM, 3 PM, 5 PM) | 10 AM | 20.2 mmHg | Standard Deviation 4.17 |