Glaucoma
Conditions
Keywords
glaucoma, ocular perfusion pressure, ocular blood flow, open angle glaucoma requiring more than one IOP-lowering medication
Brief summary
The purpose of this study was to compare the short term effects of two intraocular pressure (IOP) lowering medications on ocular perfusion pressure (OPP), ocular blood flow, intraocular pressure, and blood pressure in patients with glaucoma. Ocular perfusion pressure (OPP) is defined as the difference between arterial blood pressure (diastolic and systolic) and intraocular pressure. The primary efficacy assessment is based on diastolic ocular perfusion pressure.
Interventions
DRUGBrinzolamide 10 mg/ml/Timolol 5 mg/ml eye drops suspension
Fixed combination ophthalmic suspension
DRUGBrimonidine 20 mg/ml/Timolol 5 mg/ml eye drops solution
Fixed combination ophthalmic solution
Sponsors
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Sign Informed Consent. * Diagnosis of open-angle glaucoma in at least one eye. * Requires more than one IOP-lowering medication. * IOP measurements at Screening, Safety, and Eligibility/Period 1 Baseline Visits as specified in protocol. * Able to discontinue all IOP-lowering medication prior to Eligibility Visit and for 4 weeks between treatment periods. * Willing to complete all required study visits. * Other protocol-defined inclusion criteria may apply.
Exclusion criteria
* Female of child-bearing potential if pregnant, lactating, or not using highly effective birth control measures. * Severe central visual field loss in either eye. * Previous glaucoma surgery in the study eye. * Intraocular surgery in the study eye within 3 months prior to the Screening Visit. * Wears contact lenses. * Allergy/hypersensitivity to study medication. * Cannot safely discontinue use of glucocorticoid medication. * Uses medication that could affect IOP or blood pressure. * Recent use of high-dose aspirin. * Bronchial asthma or severe chronic obstructive pulmonary disease. * Diabetic retinopathy. * Any abnormality preventing reliable tonometry. * Any severe illness or condition unsuitable for the study, in the opinion of the investigator. * Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Overall Diastolic Ocular Perfusion Pressure at Week 6 | Week 0, Week 6 (period-based) | Diastolic ocular perfusion pressure (DOPP) is defined as the difference between diastolic arterial pressure and intraocular pressure. Diastolic arterial pressure was measured with a calibrated automated sphygmomanometer. Intraocular pressure was measured with a calibrated pneumatonometer. A lower DOPP indicates a lower optic blood supply, which can be a risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Mean Flow Value in the Superotemporal Peripapillary Retina at Week 6 | Week 0, Week 6 (period-based) | Retinal perfusion assessments were made using Heidelberg Retinal Flowmetry (HRF). Assessments were made at 4 timepoints over a 12-hour period. Intensity of blood flow was measured in arbitrary units, with a higher number indicating an increased blood flow. An increase in ocular blood flow may reduce the risk of glaucoma progression. |
| Mean Change From Baseline in Mean Flow Value in the Inverotemporal Peripapillary Retina at Week 6 | Week 0, Week 6 (period-based) | Retinal perfusion assessments were made using Heidelberg Retinal Flowmetry (HRF). Assessments were made at 4 timepoints over a 12-hour period. Intensity of blood flow was measured in arbitrary units, with a higher number indicating an increased blood flow. An increase in ocular blood flow may reduce the risk of glaucoma progression. |
| Mean Change From Baseline in Intraocular Pressure (IOP) at Week 6 | Week 0, Week 6 (period-based) | Intraocular pressure (IOP) is defined as the fluid pressure inside the eye. Intraocular pressure was measured with a calibrated pneumatonometer at 7 time points over a 24-hour period. High IOP (outside the normal range) can be a risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). |
| Mean Change From Baseline in Diastolic Blood Pressure at Week 6 | Week 0, Week 6 (period-based) | Blood pressure is defined as the pressure exerted by circulating blood upon the walls of the blood vessels, that is, arterial pressure of the systemic circulation of blood. Diastolic blood pressure refers to the minimum pressure, that is, the pressure between heartbeats. Diastolic glood pressure was measured at 7 timepoints in a 24-hour period using a calibrated sphygmomonometer. Higher blood pressure (outside the normal range) can be a risk factor for developing cardiovascular events, such as heart attack, stroke, or heart failure. Lower blood pressure (outside the normal range) can be a risk factor for dizziness or fainting. |
| Mean Change From Baseline in Systolic Blood Pressure at Week 6 | Week 0, Week 6 (period-based) | Blood pressure is defined as the pressure exerted by circulating blood upon the walls of the blood vessels, that is, arterial pressure of the systemic circulation of blood. Systolic blood pressure refers to the maximum pressure, that is, the pressure while the heart is beating, and was measured at 7 timepoints in a 24-hour period using a calibrated sphygmomonometer. Higher blood pressure (outside the normal range) can be a risk factor for developing cardiovascular events, such as heart attack, stroke, or heart failure. Lower blood pressure (outside the normal range) can be a risk factor for dizziness or fainting. |
| Mean Change From Baseline in Circadian Diastolic Ocular Perfusion Pressure at Week 6 | Week 0, Week 6 (period-based) | Circadian diastolic ocular perfusion pressure (COPP) is defined as the variations in diastolic OPP during the day and night. Diastolic ocular perfusion pressure was calculated at 7 timepoints over a 24-hour period. Changes in the diastolic ocular perfusion pressure rhythm throughout the day (outside the normal range) may affect glaucoma progression. |
| Mean Change From Baseline in Vascular Resistance in the Ophthalmic Artery at 6 Weeks | Week 0, Week 6 (period-based) | Vascular resistance in the ophthalmic artery was assessed using Color Doppler Imaging (CDI). Assessments were made at 7 time points over a 24-hour period. |
| Mean Change From Baseline in End Diastolic Velocity in the Ophthalmic Artery at Week 6 | Week 0, Week 6 (period-based) | End diastolic velocity in the ophthalmic artery was assessed using Color Doppler Imaging (CDI). Assessments were made at 7 time points over a 24-hour period. |
| Mean Change From Baseline in Peak Systolic Velocity in the Ophthalmic Artery at Week 6 | Week 0, Week 6 (period-based) | Peak systolic velocity in the ophthalmic artery was assessed using Color Doppler Imaging (CDI). Assessments were made at 7 time points over a 24-hour period. |
| Mean Change From Baseline in Peak Systolic Velocity in the Central Retinal Artery at Week 6 | Week 0, Week 6 (period-based) | Peak systolic velocity in the central retinal artery was assessed using Color Doppler Imaging (CDI). Assessments were made at 7 time points over a 24-hour period. |
| Mean Change From Baseline in Vascular Resistance in the Central Retinal Artery at Week 6 | Week 0, Week 6 (period-based) | Vascular resistance in the central retinal artery was assessed using Color Doppler Imaging (CDI). Assessments were made at 7 time points over a 24-hour period. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from and enrolled at one study center located in Greece.
Participants by arm
| Arm | Count |
|---|---|
| Overall All enrolled | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 2: 6 Weeks | Adverse Event | 0 | 1 |
| Period One: 6 Weeks | Noncompliance | 1 | 0 |
| Period One: 6 Weeks | Pt Decision Unrelated to Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Overall |
|---|---|
| Age Continuous | 65.2 years STANDARD_DEVIATION 10.3 |
| Region of Enrollment Greece | 35 participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 34 | 0 / 34 |
| serious Total, serious adverse events | 1 / 34 | 0 / 34 |
Outcome results
Primary
Mean Change From Baseline in Overall Diastolic Ocular Perfusion Pressure at Week 6
Diastolic ocular perfusion pressure (DOPP) is defined as the difference between diastolic arterial pressure and intraocular pressure. Diastolic arterial pressure was measured with a calibrated automated sphygmomanometer. Intraocular pressure was measured with a calibrated pneumatonometer. A lower DOPP indicates a lower optic blood supply, which can be a risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage).
Time frame: Week 0, Week 6 (period-based)
Population: This reporting group includes all patients who received study medication and completed the on-therapy follow-up study visit in both periods (ITT).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AZARGA | Mean Change From Baseline in Overall Diastolic Ocular Perfusion Pressure at Week 6 | 2.6 mmHg (millimeters of mercury) | Standard Error 0.78 |
| COMBIGAN | Mean Change From Baseline in Overall Diastolic Ocular Perfusion Pressure at Week 6 | 0.8 mmHg (millimeters of mercury) | Standard Error 0.779 |
Secondary
Mean Change From Baseline in Circadian Diastolic Ocular Perfusion Pressure at Week 6
Circadian diastolic ocular perfusion pressure (COPP) is defined as the variations in diastolic OPP during the day and night. Diastolic ocular perfusion pressure was calculated at 7 timepoints over a 24-hour period. Changes in the diastolic ocular perfusion pressure rhythm throughout the day (outside the normal range) may affect glaucoma progression.
Time frame: Week 0, Week 6 (period-based)
Population: This reporting group includes all patients who received study medication and completed the on-therapy follow-up study visit in both periods (ITT).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZARGA | Mean Change From Baseline in Circadian Diastolic Ocular Perfusion Pressure at Week 6 | 5:00 pm | 4.4 mmHg (millimeters of mercury) | Standard Error 1.282 |
| AZARGA | Mean Change From Baseline in Circadian Diastolic Ocular Perfusion Pressure at Week 6 | 12:00 am | 0.8 mmHg (millimeters of mercury) | Standard Error 1.282 |
| AZARGA | Mean Change From Baseline in Circadian Diastolic Ocular Perfusion Pressure at Week 6 | 1:00 pm | 3.0 mmHg (millimeters of mercury) | Standard Error 1.282 |
| AZARGA | Mean Change From Baseline in Circadian Diastolic Ocular Perfusion Pressure at Week 6 | 3:00 am | 0.3 mmHg (millimeters of mercury) | Standard Error 1.282 |
| AZARGA | Mean Change From Baseline in Circadian Diastolic Ocular Perfusion Pressure at Week 6 | 9:00 pm | 4.5 mmHg (millimeters of mercury) | Standard Error 1.282 |
| AZARGA | Mean Change From Baseline in Circadian Diastolic Ocular Perfusion Pressure at Week 6 | 6:00 am | 2.0 mmHg (millimeters of mercury) | Standard Error 1.296 |
| AZARGA | Mean Change From Baseline in Circadian Diastolic Ocular Perfusion Pressure at Week 6 | 9:00 am | 2.8 mmHg (millimeters of mercury) | Standard Error 1.282 |
| COMBIGAN | Mean Change From Baseline in Circadian Diastolic Ocular Perfusion Pressure at Week 6 | 6:00 am | 0.9 mmHg (millimeters of mercury) | Standard Error 1.282 |
| COMBIGAN | Mean Change From Baseline in Circadian Diastolic Ocular Perfusion Pressure at Week 6 | 9:00 am | 6.5 mmHg (millimeters of mercury) | Standard Error 1.282 |
| COMBIGAN | Mean Change From Baseline in Circadian Diastolic Ocular Perfusion Pressure at Week 6 | 1:00 pm | 2.1 mmHg (millimeters of mercury) | Standard Error 1.282 |
| COMBIGAN | Mean Change From Baseline in Circadian Diastolic Ocular Perfusion Pressure at Week 6 | 5:00 pm | 3.9 mmHg (millimeters of mercury) | Standard Error 1.282 |
| COMBIGAN | Mean Change From Baseline in Circadian Diastolic Ocular Perfusion Pressure at Week 6 | 9:00 pm | 2.0 mmHg (millimeters of mercury) | Standard Error 1.282 |
| COMBIGAN | Mean Change From Baseline in Circadian Diastolic Ocular Perfusion Pressure at Week 6 | 12:00 am | -5.6 mmHg (millimeters of mercury) | Standard Error 1.282 |
| COMBIGAN | Mean Change From Baseline in Circadian Diastolic Ocular Perfusion Pressure at Week 6 | 3:00 am | -4.0 mmHg (millimeters of mercury) | Standard Error 1.282 |
Secondary
Mean Change From Baseline in Diastolic Blood Pressure at Week 6
Blood pressure is defined as the pressure exerted by circulating blood upon the walls of the blood vessels, that is, arterial pressure of the systemic circulation of blood. Diastolic blood pressure refers to the minimum pressure, that is, the pressure between heartbeats. Diastolic glood pressure was measured at 7 timepoints in a 24-hour period using a calibrated sphygmomonometer. Higher blood pressure (outside the normal range) can be a risk factor for developing cardiovascular events, such as heart attack, stroke, or heart failure. Lower blood pressure (outside the normal range) can be a risk factor for dizziness or fainting.
Time frame: Week 0, Week 6 (period-based)
Population: This reporting group includes all patients who received study medication and completed the on-therapy follow-up study visit in both periods (ITT).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZARGA | Mean Change From Baseline in Diastolic Blood Pressure at Week 6 | 5:00 pm | -1.5 mmHg (millimeters of mercury) | Standard Error 1.315 |
| AZARGA | Mean Change From Baseline in Diastolic Blood Pressure at Week 6 | 12:00 am | -1.4 mmHg (millimeters of mercury) | Standard Error 1.315 |
| AZARGA | Mean Change From Baseline in Diastolic Blood Pressure at Week 6 | 1:00 pm | -3.5 mmHg (millimeters of mercury) | Standard Error 1.315 |
| AZARGA | Mean Change From Baseline in Diastolic Blood Pressure at Week 6 | 3:00 am | -1.5 mmHg (millimeters of mercury) | Standard Error 1.315 |
| AZARGA | Mean Change From Baseline in Diastolic Blood Pressure at Week 6 | 9:00 pm | -0.5 mmHg (millimeters of mercury) | Standard Error 1.315 |
| AZARGA | Mean Change From Baseline in Diastolic Blood Pressure at Week 6 | 6:00 am | -0.5 mmHg (millimeters of mercury) | Standard Error 1.334 |
| AZARGA | Mean Change From Baseline in Diastolic Blood Pressure at Week 6 | 9:00 am | -3.3 mmHg (millimeters of mercury) | Standard Error 1.315 |
| COMBIGAN | Mean Change From Baseline in Diastolic Blood Pressure at Week 6 | 6:00 am | -0.7 mmHg (millimeters of mercury) | Standard Error 1.315 |
| COMBIGAN | Mean Change From Baseline in Diastolic Blood Pressure at Week 6 | 9:00 am | 0.6 mmHg (millimeters of mercury) | Standard Error 1.315 |
| COMBIGAN | Mean Change From Baseline in Diastolic Blood Pressure at Week 6 | 1:00 pm | -4.3 mmHg (millimeters of mercury) | Standard Error 1.315 |
| COMBIGAN | Mean Change From Baseline in Diastolic Blood Pressure at Week 6 | 5:00 pm | -0.9 mmHg (millimeters of mercury) | Standard Error 1.315 |
| COMBIGAN | Mean Change From Baseline in Diastolic Blood Pressure at Week 6 | 9:00 pm | -2.1 mmHg (millimeters of mercury) | Standard Error 1.315 |
| COMBIGAN | Mean Change From Baseline in Diastolic Blood Pressure at Week 6 | 12:00 am | -7.3 mmHg (millimeters of mercury) | Standard Error 1.315 |
| COMBIGAN | Mean Change From Baseline in Diastolic Blood Pressure at Week 6 | 3:00 am | -3.8 mmHg (millimeters of mercury) | Standard Error 1.315 |
Secondary
Mean Change From Baseline in End Diastolic Velocity in the Ophthalmic Artery at Week 6
End diastolic velocity in the ophthalmic artery was assessed using Color Doppler Imaging (CDI). Assessments were made at 7 time points over a 24-hour period.
Time frame: Week 0, Week 6 (period-based)
Population: This reporting group includes all patients who received study medication and completed the on-therapy follow-up study visit in both periods (ITT). The analysis is based on patient eye-matched image data received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZARGA | Mean Change From Baseline in End Diastolic Velocity in the Ophthalmic Artery at Week 6 | 5:00 pm | 0.5 cm/s (centimeters per second) | Standard Error 0.459 |
| AZARGA | Mean Change From Baseline in End Diastolic Velocity in the Ophthalmic Artery at Week 6 | 12:00 am | -0.8 cm/s (centimeters per second) | Standard Error 0.466 |
| AZARGA | Mean Change From Baseline in End Diastolic Velocity in the Ophthalmic Artery at Week 6 | 1:00 pm | -0.6 cm/s (centimeters per second) | Standard Error 0.459 |
| AZARGA | Mean Change From Baseline in End Diastolic Velocity in the Ophthalmic Artery at Week 6 | 3:00 am | -0.1 cm/s (centimeters per second) | Standard Error 0.454 |
| AZARGA | Mean Change From Baseline in End Diastolic Velocity in the Ophthalmic Artery at Week 6 | 9:00 pm | 0.4 cm/s (centimeters per second) | Standard Error 0.454 |
| AZARGA | Mean Change From Baseline in End Diastolic Velocity in the Ophthalmic Artery at Week 6 | 6:00 am | -0.2 cm/s (centimeters per second) | Standard Error 0.466 |
| AZARGA | Mean Change From Baseline in End Diastolic Velocity in the Ophthalmic Artery at Week 6 | 9:00 am | -0.0 cm/s (centimeters per second) | Standard Error 0.454 |
| COMBIGAN | Mean Change From Baseline in End Diastolic Velocity in the Ophthalmic Artery at Week 6 | 6:00 am | -0.5 cm/s (centimeters per second) | Standard Error 0.448 |
| COMBIGAN | Mean Change From Baseline in End Diastolic Velocity in the Ophthalmic Artery at Week 6 | 9:00 am | -0.8 cm/s (centimeters per second) | Standard Error 0.448 |
| COMBIGAN | Mean Change From Baseline in End Diastolic Velocity in the Ophthalmic Artery at Week 6 | 1:00 pm | -1.2 cm/s (centimeters per second) | Standard Error 0.46 |
| COMBIGAN | Mean Change From Baseline in End Diastolic Velocity in the Ophthalmic Artery at Week 6 | 5:00 pm | 0.2 cm/s (centimeters per second) | Standard Error 0.466 |
| COMBIGAN | Mean Change From Baseline in End Diastolic Velocity in the Ophthalmic Artery at Week 6 | 9:00 pm | -0.8 cm/s (centimeters per second) | Standard Error 0.448 |
| COMBIGAN | Mean Change From Baseline in End Diastolic Velocity in the Ophthalmic Artery at Week 6 | 12:00 am | -1.4 cm/s (centimeters per second) | Standard Error 0.454 |
| COMBIGAN | Mean Change From Baseline in End Diastolic Velocity in the Ophthalmic Artery at Week 6 | 3:00 am | -0.6 cm/s (centimeters per second) | Standard Error 0.459 |
Secondary
Mean Change From Baseline in Intraocular Pressure (IOP) at Week 6
Intraocular pressure (IOP) is defined as the fluid pressure inside the eye. Intraocular pressure was measured with a calibrated pneumatonometer at 7 time points over a 24-hour period. High IOP (outside the normal range) can be a risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage).
Time frame: Week 0, Week 6 (period-based)
Population: This reporting group includes all patients who received study medication and completed the on-therapy follow-up study visit in both periods (ITT).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZARGA | Mean Change From Baseline in Intraocular Pressure (IOP) at Week 6 | 1:00 pm | -6.0 mmHg (millimeters of mercury) | Standard Error 0.661 |
| AZARGA | Mean Change From Baseline in Intraocular Pressure (IOP) at Week 6 | 12:00 am | -1.9 mmHg (millimeters of mercury) | Standard Error 0.661 |
| AZARGA | Mean Change From Baseline in Intraocular Pressure (IOP) at Week 6 | 9:00 am | -6.3 mmHg (millimeters of mercury) | Standard Error 0.661 |
| AZARGA | Mean Change From Baseline in Intraocular Pressure (IOP) at Week 6 | 3:00 am | -1.3 mmHg (millimeters of mercury) | Standard Error 0.661 |
| AZARGA | Mean Change From Baseline in Intraocular Pressure (IOP) at Week 6 | 9:00 pm | -4.3 mmHg (millimeters of mercury) | Standard Error 0.661 |
| AZARGA | Mean Change From Baseline in Intraocular Pressure (IOP) at Week 6 | 6:00 am | -2.3 mmHg (millimeters of mercury) | Standard Error 0.668 |
| AZARGA | Mean Change From Baseline in Intraocular Pressure (IOP) at Week 6 | 5:00 pm | -5.6 mmHg (millimeters of mercury) | Standard Error 0.661 |
| COMBIGAN | Mean Change From Baseline in Intraocular Pressure (IOP) at Week 6 | 6:00 am | -1.2 mmHg (millimeters of mercury) | Standard Error 0.661 |
| COMBIGAN | Mean Change From Baseline in Intraocular Pressure (IOP) at Week 6 | 5:00 pm | -5.2 mmHg (millimeters of mercury) | Standard Error 0.661 |
| COMBIGAN | Mean Change From Baseline in Intraocular Pressure (IOP) at Week 6 | 9:00 am | -6.5 mmHg (millimeters of mercury) | Standard Error 0.661 |
| COMBIGAN | Mean Change From Baseline in Intraocular Pressure (IOP) at Week 6 | 1:00 pm | -6.5 mmHg (millimeters of mercury) | Standard Error 0.661 |
| COMBIGAN | Mean Change From Baseline in Intraocular Pressure (IOP) at Week 6 | 9:00 pm | -4.9 mmHg (millimeters of mercury) | Standard Error 0.661 |
| COMBIGAN | Mean Change From Baseline in Intraocular Pressure (IOP) at Week 6 | 12:00 am | -1.6 mmHg (millimeters of mercury) | Standard Error 0.661 |
| COMBIGAN | Mean Change From Baseline in Intraocular Pressure (IOP) at Week 6 | 3:00 am | -0.6 mmHg (millimeters of mercury) | Standard Error 0.661 |
Secondary
Mean Change From Baseline in Mean Flow Value in the Inverotemporal Peripapillary Retina at Week 6
Retinal perfusion assessments were made using Heidelberg Retinal Flowmetry (HRF). Assessments were made at 4 timepoints over a 12-hour period. Intensity of blood flow was measured in arbitrary units, with a higher number indicating an increased blood flow. An increase in ocular blood flow may reduce the risk of glaucoma progression.
Time frame: Week 0, Week 6 (period-based)
Population: This reporting group includes all patients who received study medication and completed the on-therapy follow-up study visit in both periods (ITT). The analysis is based on patient eye-matched image data received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZARGA | Mean Change From Baseline in Mean Flow Value in the Inverotemporal Peripapillary Retina at Week 6 | 9:00 am | 15.9 Arbitrary Units | Standard Error 92.064 |
| AZARGA | Mean Change From Baseline in Mean Flow Value in the Inverotemporal Peripapillary Retina at Week 6 | 1:00 pm | -40.7 Arbitrary Units | Standard Error 89.642 |
| AZARGA | Mean Change From Baseline in Mean Flow Value in the Inverotemporal Peripapillary Retina at Week 6 | 5:00 pm | -38.7 Arbitrary Units | Standard Error 88.363 |
| AZARGA | Mean Change From Baseline in Mean Flow Value in the Inverotemporal Peripapillary Retina at Week 6 | 9:00 pm | 182.3 Arbitrary Units | Standard Error 92.064 |
| COMBIGAN | Mean Change From Baseline in Mean Flow Value in the Inverotemporal Peripapillary Retina at Week 6 | 9:00 pm | -91.0 Arbitrary Units | Standard Error 92.064 |
| COMBIGAN | Mean Change From Baseline in Mean Flow Value in the Inverotemporal Peripapillary Retina at Week 6 | 9:00 am | -70.0 Arbitrary Units | Standard Error 89.642 |
| COMBIGAN | Mean Change From Baseline in Mean Flow Value in the Inverotemporal Peripapillary Retina at Week 6 | 5:00 pm | -69.1 Arbitrary Units | Standard Error 92.61 |
| COMBIGAN | Mean Change From Baseline in Mean Flow Value in the Inverotemporal Peripapillary Retina at Week 6 | 1:00 pm | -89.2 Arbitrary Units | Standard Error 95.324 |
Secondary
Mean Change From Baseline in Mean Flow Value in the Superotemporal Peripapillary Retina at Week 6
Retinal perfusion assessments were made using Heidelberg Retinal Flowmetry (HRF). Assessments were made at 4 timepoints over a 12-hour period. Intensity of blood flow was measured in arbitrary units, with a higher number indicating an increased blood flow. An increase in ocular blood flow may reduce the risk of glaucoma progression.
Time frame: Week 0, Week 6 (period-based)
Population: This reporting group includes all patients who received study medication and completed the on-therapy follow-up study visit in both periods (ITT). The analysis is based on patient eye-matched image data received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZARGA | Mean Change From Baseline in Mean Flow Value in the Superotemporal Peripapillary Retina at Week 6 | 9:00 am | -272.4 Arbitrary Units | Standard Error 146.294 |
| AZARGA | Mean Change From Baseline in Mean Flow Value in the Superotemporal Peripapillary Retina at Week 6 | 1:00 pm | -12.1 Arbitrary Units | Standard Error 142.844 |
| AZARGA | Mean Change From Baseline in Mean Flow Value in the Superotemporal Peripapillary Retina at Week 6 | 5:00 pm | -26.7 Arbitrary Units | Standard Error 144.914 |
| AZARGA | Mean Change From Baseline in Mean Flow Value in the Superotemporal Peripapillary Retina at Week 6 | 9:00 pm | 14.0 Arbitrary Units | Standard Error 148.317 |
| COMBIGAN | Mean Change From Baseline in Mean Flow Value in the Superotemporal Peripapillary Retina at Week 6 | 9:00 pm | -33.2 Arbitrary Units | Standard Error 144.451 |
| COMBIGAN | Mean Change From Baseline in Mean Flow Value in the Superotemporal Peripapillary Retina at Week 6 | 9:00 am | -43.5 Arbitrary Units | Standard Error 146.586 |
| COMBIGAN | Mean Change From Baseline in Mean Flow Value in the Superotemporal Peripapillary Retina at Week 6 | 5:00 pm | -51.3 Arbitrary Units | Standard Error 142.844 |
| COMBIGAN | Mean Change From Baseline in Mean Flow Value in the Superotemporal Peripapillary Retina at Week 6 | 1:00 pm | 248.9 Arbitrary Units | Standard Error 144.917 |
Secondary
Mean Change From Baseline in Peak Systolic Velocity in the Central Retinal Artery at Week 6
Peak systolic velocity in the central retinal artery was assessed using Color Doppler Imaging (CDI). Assessments were made at 7 time points over a 24-hour period.
Time frame: Week 0, Week 6 (period-based)
Population: This reporting group includes all patients who received study medication and completed the on-therapy follow-up study visit in both periods (ITT). The analysis is based on patient eye-matched image data received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZARGA | Mean Change From Baseline in Peak Systolic Velocity in the Central Retinal Artery at Week 6 | 5:00 pm | 1.0 cm/s (centimeters per second) | Standard Error 0.577 |
| AZARGA | Mean Change From Baseline in Peak Systolic Velocity in the Central Retinal Artery at Week 6 | 12:00 am | 1.9 cm/s (centimeters per second) | Standard Error 0.577 |
| AZARGA | Mean Change From Baseline in Peak Systolic Velocity in the Central Retinal Artery at Week 6 | 1:00 pm | -0.2 cm/s (centimeters per second) | Standard Error 0.577 |
| AZARGA | Mean Change From Baseline in Peak Systolic Velocity in the Central Retinal Artery at Week 6 | 3:00 am | 0.2 cm/s (centimeters per second) | Standard Error 0.565 |
| AZARGA | Mean Change From Baseline in Peak Systolic Velocity in the Central Retinal Artery at Week 6 | 9:00 pm | 0.9 cm/s (centimeters per second) | Standard Error 0.565 |
| AZARGA | Mean Change From Baseline in Peak Systolic Velocity in the Central Retinal Artery at Week 6 | 6:00 am | 0.2 cm/s (centimeters per second) | Standard Error 0.571 |
| AZARGA | Mean Change From Baseline in Peak Systolic Velocity in the Central Retinal Artery at Week 6 | 9:00 am | 0.9 cm/s (centimeters per second) | Standard Error 0.571 |
| COMBIGAN | Mean Change From Baseline in Peak Systolic Velocity in the Central Retinal Artery at Week 6 | 6:00 am | 0.9 cm/s (centimeters per second) | Standard Error 0.565 |
| COMBIGAN | Mean Change From Baseline in Peak Systolic Velocity in the Central Retinal Artery at Week 6 | 9:00 am | 0.7 cm/s (centimeters per second) | Standard Error 0.565 |
| COMBIGAN | Mean Change From Baseline in Peak Systolic Velocity in the Central Retinal Artery at Week 6 | 1:00 pm | 0.3 cm/s (centimeters per second) | Standard Error 0.578 |
| COMBIGAN | Mean Change From Baseline in Peak Systolic Velocity in the Central Retinal Artery at Week 6 | 5:00 pm | 0.6 cm/s (centimeters per second) | Standard Error 0.565 |
| COMBIGAN | Mean Change From Baseline in Peak Systolic Velocity in the Central Retinal Artery at Week 6 | 9:00 pm | -0.5 cm/s (centimeters per second) | Standard Error 0.565 |
| COMBIGAN | Mean Change From Baseline in Peak Systolic Velocity in the Central Retinal Artery at Week 6 | 12:00 am | -0.5 cm/s (centimeters per second) | Standard Error 0.565 |
| COMBIGAN | Mean Change From Baseline in Peak Systolic Velocity in the Central Retinal Artery at Week 6 | 3:00 am | -1.1 cm/s (centimeters per second) | Standard Error 0.57 |
Secondary
Mean Change From Baseline in Peak Systolic Velocity in the Ophthalmic Artery at Week 6
Peak systolic velocity in the ophthalmic artery was assessed using Color Doppler Imaging (CDI). Assessments were made at 7 time points over a 24-hour period.
Time frame: Week 0, Week 6 (period-based)
Population: This reporting group includes all patients who received study medication and completed the on-therapy follow-up study visit in both periods (ITT). The analysis is based on patient eye-matched image data received.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| AZARGA | Mean Change From Baseline in Peak Systolic Velocity in the Ophthalmic Artery at Week 6 | 5:00 pm | 2.2 cm/s (centimeters per second) | Standard Error 1.251 |
| AZARGA | Mean Change From Baseline in Peak Systolic Velocity in the Ophthalmic Artery at Week 6 | 12:00 am | -2.3 cm/s (centimeters per second) | Standard Error 1.268 |
| AZARGA | Mean Change From Baseline in Peak Systolic Velocity in the Ophthalmic Artery at Week 6 | 1:00 pm | -0.7 cm/s (centimeters per second) | Standard Error 1.251 |
| AZARGA | Mean Change From Baseline in Peak Systolic Velocity in the Ophthalmic Artery at Week 6 | 3:00 am | 0.2 cm/s (centimeters per second) | Standard Error 1.235 |
| AZARGA | Mean Change From Baseline in Peak Systolic Velocity in the Ophthalmic Artery at Week 6 | 9:00 pm | 2.2 cm/s (centimeters per second) | Standard Error 1.237 |
| AZARGA | Mean Change From Baseline in Peak Systolic Velocity in the Ophthalmic Artery at Week 6 | 6:00 am | -0.6 cm/s (centimeters per second) | Standard Error 1.267 |
| AZARGA | Mean Change From Baseline in Peak Systolic Velocity in the Ophthalmic Artery at Week 6 | 9:00 am | -1.0 cm/s (centimeters per second) | Standard Error 1.237 |
| COMBIGAN | Mean Change From Baseline in Peak Systolic Velocity in the Ophthalmic Artery at Week 6 | 6:00 am | 1.5 cm/s (centimeters per second) | Standard Error 1.221 |
| COMBIGAN | Mean Change From Baseline in Peak Systolic Velocity in the Ophthalmic Artery at Week 6 | 9:00 am | -3.8 cm/s (centimeters per second) | Standard Error 1.221 |
| COMBIGAN | Mean Change From Baseline in Peak Systolic Velocity in the Ophthalmic Artery at Week 6 | 1:00 pm | -1.4 cm/s (centimeters per second) | Standard Error 1.254 |
| COMBIGAN | Mean Change From Baseline in Peak Systolic Velocity in the Ophthalmic Artery at Week 6 | 5:00 pm | 1.3 cm/s (centimeters per second) | Standard Error 1.267 |
| COMBIGAN | Mean Change From Baseline in Peak Systolic Velocity in the Ophthalmic Artery at Week 6 | 9:00 pm | -1.4 cm/s (centimeters per second) | Standard Error 1.221 |
| COMBIGAN | Mean Change From Baseline in Peak Systolic Velocity in the Ophthalmic Artery at Week 6 | 12:00 am | -3.1 cm/s (centimeters per second) | Standard Error 1.235 |
| COMBIGAN | Mean Change From Baseline in Peak Systolic Velocity in the Ophthalmic Artery at Week 6 | 3:00 am | 0.0 cm/s (centimeters per second) | Standard Error 1.25 |
Secondary
Mean Change From Baseline in Systolic Blood Pressure at Week 6
Blood pressure is defined as the pressure exerted by circulating blood upon the walls of the blood vessels, that is, arterial pressure of the systemic circulation of blood. Systolic blood pressure refers to the maximum pressure, that is, the pressure while the heart is beating, and was measured at 7 timepoints in a 24-hour period using a calibrated sphygmomonometer. Higher blood pressure (outside the normal range) can be a risk factor for developing cardiovascular events, such as heart attack, stroke, or heart failure. Lower blood pressure (outside the normal range) can be a risk factor for dizziness or fainting.
Time frame: Week 0, Week 6 (period-based)
Population: This reporting group includes all patients who received study medication and completed the on-therapy follow-up study visit in both periods (ITT).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZARGA | Mean Change From Baseline in Systolic Blood Pressure at Week 6 | 9:00 pm | -1.4 mmHg (millimeters of mercury) | Standard Error 2.134 |
| AZARGA | Mean Change From Baseline in Systolic Blood Pressure at Week 6 | 9:00 am | -4.2 mmHg (millimeters of mercury) | Standard Error 2.134 |
| AZARGA | Mean Change From Baseline in Systolic Blood Pressure at Week 6 | 12:00 am | -2.9 mmHg (millimeters of mercury) | Standard Error 2.134 |
| AZARGA | Mean Change From Baseline in Systolic Blood Pressure at Week 6 | 5:00 pm | -2.9 mmHg (millimeters of mercury) | Standard Error 2.134 |
| AZARGA | Mean Change From Baseline in Systolic Blood Pressure at Week 6 | 3:00 am | -2.9 mmHg (millimeters of mercury) | Standard Error 2.134 |
| AZARGA | Mean Change From Baseline in Systolic Blood Pressure at Week 6 | 6:00 am | -0.1 mmHg (millimeters of mercury) | Standard Error 2.165 |
| AZARGA | Mean Change From Baseline in Systolic Blood Pressure at Week 6 | 1:00 pm | -2.6 mmHg (millimeters of mercury) | Standard Error 2.134 |
| COMBIGAN | Mean Change From Baseline in Systolic Blood Pressure at Week 6 | 6:00 am | 3.0 mmHg (millimeters of mercury) | Standard Error 2.134 |
| COMBIGAN | Mean Change From Baseline in Systolic Blood Pressure at Week 6 | 9:00 am | 4.5 mmHg (millimeters of mercury) | Standard Error 2.134 |
| COMBIGAN | Mean Change From Baseline in Systolic Blood Pressure at Week 6 | 1:00 pm | -1.9 mmHg (millimeters of mercury) | Standard Error 2.134 |
| COMBIGAN | Mean Change From Baseline in Systolic Blood Pressure at Week 6 | 5:00 pm | -0.4 mmHg (millimeters of mercury) | Standard Error 2.134 |
| COMBIGAN | Mean Change From Baseline in Systolic Blood Pressure at Week 6 | 9:00 pm | -0.6 mmHg (millimeters of mercury) | Standard Error 2.134 |
| COMBIGAN | Mean Change From Baseline in Systolic Blood Pressure at Week 6 | 12:00 am | -12.2 mmHg (millimeters of mercury) | Standard Error 2.134 |
| COMBIGAN | Mean Change From Baseline in Systolic Blood Pressure at Week 6 | 3:00 am | -3.0 mmHg (millimeters of mercury) | Standard Error 2.134 |
Secondary
Mean Change From Baseline in Vascular Resistance in the Central Retinal Artery at Week 6
Vascular resistance in the central retinal artery was assessed using Color Doppler Imaging (CDI). Assessments were made at 7 time points over a 24-hour period.
Time frame: Week 0, Week 6 (period-based)
Population: This reporting group includes all patients who received study medication and completed the on-therapy follow-up study visit in both periods (ITT). The analysis is based on patient eye-matched image data received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZARGA | Mean Change From Baseline in Vascular Resistance in the Central Retinal Artery at Week 6 | 5:00 pm | 0.00 cm/s (centimeters per second) | Standard Error 0.014 |
| AZARGA | Mean Change From Baseline in Vascular Resistance in the Central Retinal Artery at Week 6 | 12:00 am | 0.02 cm/s (centimeters per second) | Standard Error 0.014 |
| AZARGA | Mean Change From Baseline in Vascular Resistance in the Central Retinal Artery at Week 6 | 1:00 pm | -0.01 cm/s (centimeters per second) | Standard Error 0.014 |
| AZARGA | Mean Change From Baseline in Vascular Resistance in the Central Retinal Artery at Week 6 | 3:00 am | 0.01 cm/s (centimeters per second) | Standard Error 0.014 |
| AZARGA | Mean Change From Baseline in Vascular Resistance in the Central Retinal Artery at Week 6 | 9:00 pm | 0.00 cm/s (centimeters per second) | Standard Error 0.014 |
| AZARGA | Mean Change From Baseline in Vascular Resistance in the Central Retinal Artery at Week 6 | 6:00 am | -0.02 cm/s (centimeters per second) | Standard Error 0.014 |
| AZARGA | Mean Change From Baseline in Vascular Resistance in the Central Retinal Artery at Week 6 | 9:00 am | -0.00 cm/s (centimeters per second) | Standard Error 0.014 |
| COMBIGAN | Mean Change From Baseline in Vascular Resistance in the Central Retinal Artery at Week 6 | 6:00 am | 0.02 cm/s (centimeters per second) | Standard Error 0.014 |
| COMBIGAN | Mean Change From Baseline in Vascular Resistance in the Central Retinal Artery at Week 6 | 9:00 am | 0.01 cm/s (centimeters per second) | Standard Error 0.014 |
| COMBIGAN | Mean Change From Baseline in Vascular Resistance in the Central Retinal Artery at Week 6 | 1:00 pm | 0.01 cm/s (centimeters per second) | Standard Error 0.014 |
| COMBIGAN | Mean Change From Baseline in Vascular Resistance in the Central Retinal Artery at Week 6 | 5:00 pm | -0.00 cm/s (centimeters per second) | Standard Error 0.014 |
| COMBIGAN | Mean Change From Baseline in Vascular Resistance in the Central Retinal Artery at Week 6 | 9:00 pm | 0.02 cm/s (centimeters per second) | Standard Error 0.014 |
| COMBIGAN | Mean Change From Baseline in Vascular Resistance in the Central Retinal Artery at Week 6 | 12:00 am | -0.01 cm/s (centimeters per second) | Standard Error 0.014 |
| COMBIGAN | Mean Change From Baseline in Vascular Resistance in the Central Retinal Artery at Week 6 | 3:00 am | 0.01 cm/s (centimeters per second) | Standard Error 0.014 |
Secondary
Mean Change From Baseline in Vascular Resistance in the Ophthalmic Artery at 6 Weeks
Vascular resistance in the ophthalmic artery was assessed using Color Doppler Imaging (CDI). Assessments were made at 7 time points over a 24-hour period.
Time frame: Week 0, Week 6 (period-based)
Population: This reporting group includes all patients who received study medication and completed the on-therapy follow-up study visit in both periods (ITT). The analysis is based on patient eye-matched image data received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| AZARGA | Mean Change From Baseline in Vascular Resistance in the Ophthalmic Artery at 6 Weeks | 1:00 pm | 0.02 cm/s (centimeters per second) | Standard Error 0.012 |
| AZARGA | Mean Change From Baseline in Vascular Resistance in the Ophthalmic Artery at 6 Weeks | 9:00 pm | 0.01 cm/s (centimeters per second) | Standard Error 0.012 |
| AZARGA | Mean Change From Baseline in Vascular Resistance in the Ophthalmic Artery at 6 Weeks | 9:00 am | -0.01 cm/s (centimeters per second) | Standard Error 0.012 |
| AZARGA | Mean Change From Baseline in Vascular Resistance in the Ophthalmic Artery at 6 Weeks | 12:00 am | -0.01 cm/s (centimeters per second) | Standard Error 0.012 |
| AZARGA | Mean Change From Baseline in Vascular Resistance in the Ophthalmic Artery at 6 Weeks | 5:00 pm | 0.01 cm/s (centimeters per second) | Standard Error 0.012 |
| AZARGA | Mean Change From Baseline in Vascular Resistance in the Ophthalmic Artery at 6 Weeks | 3:00 am | 0.01 cm/s (centimeters per second) | Standard Error 0.012 |
| AZARGA | Mean Change From Baseline in Vascular Resistance in the Ophthalmic Artery at 6 Weeks | 6:00 am | 0.01 cm/s (centimeters per second) | Standard Error 0.012 |
| COMBIGAN | Mean Change From Baseline in Vascular Resistance in the Ophthalmic Artery at 6 Weeks | 3:00 am | 0.03 cm/s (centimeters per second) | Standard Error 0.012 |
| COMBIGAN | Mean Change From Baseline in Vascular Resistance in the Ophthalmic Artery at 6 Weeks | 6:00 am | 0.03 cm/s (centimeters per second) | Standard Error 0.011 |
| COMBIGAN | Mean Change From Baseline in Vascular Resistance in the Ophthalmic Artery at 6 Weeks | 9:00 am | -0.01 cm/s (centimeters per second) | Standard Error 0.011 |
| COMBIGAN | Mean Change From Baseline in Vascular Resistance in the Ophthalmic Artery at 6 Weeks | 1:00 pm | 0.02 cm/s (centimeters per second) | Standard Error 0.012 |
| COMBIGAN | Mean Change From Baseline in Vascular Resistance in the Ophthalmic Artery at 6 Weeks | 5:00 pm | 0.01 cm/s (centimeters per second) | Standard Error 0.012 |
| COMBIGAN | Mean Change From Baseline in Vascular Resistance in the Ophthalmic Artery at 6 Weeks | 9:00 pm | 0.01 cm/s (centimeters per second) | Standard Error 0.011 |
| COMBIGAN | Mean Change From Baseline in Vascular Resistance in the Ophthalmic Artery at 6 Weeks | 12:00 am | 0.02 cm/s (centimeters per second) | Standard Error 0.012 |