Circadian Ocular Perfusion Pressure and Ocular Blood Flow

• Sponsor: Alcon Research (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00800540
• Collaborator: (none)
• Enrollment: 35
• Location: 1
• Arms: 2
• Duration (Months): 35
• Patients Per Site Per Month: 1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Glaucoma	Drug: Brinzolamide 10 mg/ml/Timolol 5 mg/ml eye drops suspension; Drug: Brimonidine 20 mg/ml/Timolol 5 mg/ml eye drops solution	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Effects of Topical Hypotensive Drugs on Circadian Ocular Perfusion Pressure and Ocular Blood Flow in Patients With Open-Angle Glaucoma
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Other: AZARGA/COMBIGAN AZARGA, followed by COMBIGAN, as randomized. Each fixed combination instilled in the study eye, one drop twice daily (9:00 and 21:00), for six weeks, with a 4-week washout period separating the two treatment periods.	Drug: Brinzolamide 10 mg/ml/Timolol 5 mg/ml eye drops suspension; Fixed combination ophthalmic suspension; Other Names: AZARGA™ ; Drug: Brimonidine 20 mg/ml/Timolol 5 mg/ml eye drops solution; Fixed combination ophthalmic solution; Other Names: COMBIGAN®
Other: COMBIGAN/AZARGA COMBIGAN, followed by AZARGA, as randomized. Each fixed combination instilled in the study eye, one drop twice daily (9:00 and 21:00), for six weeks, with a 4-week washout period separating the two treatment periods.	Drug: Brinzolamide 10 mg/ml/Timolol 5 mg/ml eye drops suspension; Fixed combination ophthalmic suspension; Other Names: AZARGA™ ; Drug: Brimonidine 20 mg/ml/Timolol 5 mg/ml eye drops solution; Fixed combination ophthalmic solution; Other Names: COMBIGAN®

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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).

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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 exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Contact Alcon Call Center at 1-888-451-3937 For Trial Locations	Fort Worth	Texas	United States	76134

Sponsors and Collaborators

• Alcon Research

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alcon Research
• ClinicalTrials.gov Identifier: NCT00800540
• Other Study ID Numbers: C-07-16; 2007-005936-99
• First Posted: Dec 2, 2008
• Last Update Posted: Mar 22, 2013
• Last Verified: Mar 1, 2013

• Keywords provided by Alcon Research: glaucoma; ocular perfusion pressure; ocular blood flow; open angle glaucoma requiring more than one IOP-lowering medication
• Additional relevant MeSH terms: Glaucoma; Timolol; Brimonidine Tartrate; Ophthalmic Solutions; Brinzolamide

Study Results

Participant Flow

Recruitment Details	Participants were recruited from and enrolled at one study center located in Greece.

Arm/Group Title	AZARGA/COMBIGAN	COMBIGAN/AZARGA
Arm/Group Description	AZARGA, followed by COMBIGAN, as randomized. Each fixed combination was used for 6 weeks, with a 4-week washout period separating the two treatment periods.	COMBIGAN, followed by AZARGA, as randomized. Each fixed combination was used for 6 weeks, with a 4-week washout period separating the two treatment periods.
Period Title: Period One: 6 Weeks
STARTED	17	18
COMPLETED	16	17
NOT COMPLETED	1	1
Period Title: Period One: 6 Weeks
STARTED	16	17
COMPLETED	16	17
NOT COMPLETED	0	0
Period Title: Period One: 6 Weeks
STARTED	16	17
COMPLETED	16	16
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Overall
Arm/Group Description	All enrolled
Overall Participants	35
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.2 (10.3)
Sex: Female, Male (Count of Participants)
Female	19 54.3%
Male	16 45.7%
Region of Enrollment (participants) [Number]
Greece	35 100%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in Overall Diastolic Ocular Perfusion Pressure at Week 6
Description	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)

Outcome Measure Data

Analysis Population Description

This reporting group includes all patients who received study medication and completed the on-therapy follow-up study visit in both periods (ITT).

Arm/Group Title	AZARGA	COMBIGAN
Arm/Group Description	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks
Measure Participants	32	32
Measure eyes	41	41
Mean (Standard Error) [mmHg (millimeters of mercury)]	2.6 (0.780)	0.8 (0.779)

2. Secondary Outcome

Title	Mean Change From Baseline in Circadian Diastolic Ocular Perfusion Pressure at Week 6
Description	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)

Outcome Measure Data

Analysis Population Description

This reporting group includes all patients who received study medication and completed the on-therapy follow-up study visit in both periods (ITT).

Arm/Group Title	AZARGA	COMBIGAN
Arm/Group Description	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks
Measure Participants	32	32
Measure eyes	41	41
9:00 am	2.8 (1.282)	6.5 (1.282)
1:00 pm	3.0 (1.282)	2.1 (1.282)
5:00 pm	4.4 (1.282)	3.9 (1.282)
9:00 pm	4.5 (1.282)	2.0 (1.282)
12:00 am	0.8 (1.282)	-5.6 (1.282)
3:00 am	0.3 (1.282)	-4.0 (1.282)
6:00 am	2.0 (1.296)	0.9 (1.282)

3. Secondary Outcome

Title	Mean Change From Baseline in Mean Flow Value in the Superotemporal Peripapillary Retina at Week 6
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	AZARGA	COMBIGAN
Arm/Group Description	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks
Measure Participants	32	32
Measure eyes	41	41
9:00 am	-272.4 (146.294)	-43.5 (146.586)
1:00 pm	-12.1 (142.844)	248.9 (144.917)
5:00 pm	-26.7 (144.914)	-51.3 (142.844)
9:00 pm	14.0 (148.317)	-33.2 (144.451)

4. Secondary Outcome

Title	Mean Change From Baseline in Mean Flow Value in the Inverotemporal Peripapillary Retina at Week 6
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	AZARGA	COMBIGAN
Arm/Group Description	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks
Measure Participants	32	32
Measure eyes	41	41
9:00 am	15.9 (92.064)	-70.0 (89.642)
1:00 pm	-40.7 (89.642)	-89.2 (95.324)
5:00 pm	-38.7 (88.363)	-69.1 (92.610)
9:00 pm	182.3 (92.064)	-91.0 (92.064)

5. Secondary Outcome

Title	Mean Change From Baseline in Intraocular Pressure (IOP) at Week 6
Description	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)

Outcome Measure Data

Analysis Population Description

This reporting group includes all patients who received study medication and completed the on-therapy follow-up study visit in both periods (ITT).

Arm/Group Title	AZARGA	COMBIGAN
Arm/Group Description	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks
Measure Participants	32	32
Measure eyes	41	41
9:00 am	-6.3 (0.661)	-6.5 (0.661)
1:00 pm	-6.0 (0.661)	-6.5 (0.661)
5:00 pm	-5.6 (0.661)	-5.2 (0.661)
9:00 pm	-4.3 (0.661)	-4.9 (0.661)
12:00 am	-1.9 (0.661)	-1.6 (0.661)
3:00 am	-1.3 (0.661)	-0.6 (0.661)
6:00 am	-2.3 (0.668)	-1.2 (0.661)

6. Secondary Outcome

Title	Mean Change From Baseline in Diastolic Blood Pressure at Week 6
Description	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)

Outcome Measure Data

Analysis Population Description

This reporting group includes all patients who received study medication and completed the on-therapy follow-up study visit in both periods (ITT).

Arm/Group Title	AZARGA	COMBIGAN
Arm/Group Description	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks
Measure Participants	32	32
9:00 am	-3.3 (1.315)	0.6 (1.315)
1:00 pm	-3.5 (1.315)	-4.3 (1.315)
5:00 pm	-1.5 (1.315)	-0.9 (1.315)
9:00 pm	-0.5 (1.315)	-2.1 (1.315)
12:00 am	-1.4 (1.315)	-7.3 (1.315)
3:00 am	-1.5 (1.315)	-3.8 (1.315)
6:00 am	-0.5 (1.334)	-0.7 (1.315)

7. Secondary Outcome

Title	Mean Change From Baseline in Systolic Blood Pressure at Week 6
Description	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)

Outcome Measure Data

Analysis Population Description

This reporting group includes all patients who received study medication and completed the on-therapy follow-up study visit in both periods (ITT).

Arm/Group Title	AZARGA	COMBIGAN
Arm/Group Description	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks
Measure Participants	32	32
9:00 am	-4.2 (2.134)	4.5 (2.134)
1:00 pm	-2.6 (2.134)	-1.9 (2.134)
5:00 pm	-2.9 (2.134)	-0.4 (2.134)
9:00 pm	-1.4 (2.134)	-0.6 (2.134)
12:00 am	-2.9 (2.134)	-12.2 (2.134)
3:00 am	-2.9 (2.134)	-3.0 (2.134)
6:00 am	-0.1 (2.165)	3.0 (2.134)

8. Secondary Outcome

Title	Mean Change From Baseline in Vascular Resistance in the Central Retinal Artery at Week 6
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	AZARGA	COMBIGAN
Arm/Group Description	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks
Measure Participants	32	32
Measure eyes	41	41
9:00 am	-0.00 (0.014)	0.01 (0.014)
1:00 pm	-0.01 (0.014)	0.01 (0.014)
5:00 pm	0.00 (0.014)	-0.00 (0.014)
9:00 pm	0.00 (0.014)	0.02 (0.014)
12:00 am	0.02 (0.014)	-0.01 (0.014)
3:00 am	0.01 (0.014)	0.01 (0.014)
6:00 am	-0.02 (0.014)	0.02 (0.014)

9. Secondary Outcome

Title	Mean Change From Baseline in Vascular Resistance in the Ophthalmic Artery at 6 Weeks
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	AZARGA	COMBIGAN
Arm/Group Description	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks
Measure Participants	32	32
Measure eyes	41	41
9:00 am	-0.01 (0.012)	-0.01 (0.011)
1:00 pm	0.02 (0.012)	0.02 (0.012)
5:00 pm	0.01 (0.012)	0.01 (0.012)
9:00 pm	0.01 (0.012)	0.01 (0.011)
12:00 am	-0.01 (0.012)	0.02 (0.012)
3:00 am	0.01 (0.012)	0.03 (0.012)
6:00 am	0.01 (0.012)	0.03 (0.011)

10. Secondary Outcome

Title	Mean Change From Baseline in End Diastolic Velocity in the Ophthalmic Artery at Week 6
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	AZARGA	COMBIGAN
Arm/Group Description	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks
Measure Participants	32	32
Measure eyes	41	41
9:00 am	-0.0 (0.454)	-0.8 (0.448)
1:00 pm	-0.6 (0.459)	-1.2 (0.460)
5:00 pm	0.5 (0.459)	0.2 (0.466)
9:00 pm	0.4 (0.454)	-0.8 (0.448)
12:00 am	-0.8 (0.466)	-1.4 (0.454)
3:00 am	-0.1 (0.454)	-0.6 (0.459)
6:00 am	-0.2 (0.466)	-0.5 (0.448)

11. Secondary Outcome

Title	Mean Change From Baseline in Peak Systolic Velocity in the Ophthalmic Artery at Week 6
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	AZARGA	COMBIGAN
Arm/Group Description	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks
Measure Participants	32	32
Measure eyes	41	41
9:00 am	-1.0 (1.237)	-3.8 (1.221)
1:00 pm	-0.7 (1.251)	-1.4 (1.254)
5:00 pm	2.2 (1.251)	1.3 (1.267)
9:00 pm	2.2 (1.237)	-1.4 (1.221)
12:00 am	-2.3 (1.268)	-3.1 (1.235)
3:00 am	0.2 (1.235)	0.0 (1.250)
6:00 am	-0.6 (1.267)	1.5 (1.221)

12. Secondary Outcome

Title	Mean Change From Baseline in Peak Systolic Velocity in the Central Retinal Artery at Week 6
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	AZARGA	COMBIGAN
Arm/Group Description	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks
Measure Participants	32	32
Measure eyes	41	41
9:00 am	0.9 (0.571)	0.7 (0.565)
1:00 pm	-0.2 (0.577)	0.3 (0.578)
5:00 pm	1.0 (0.577)	0.6 (0.565)
9:00 pm	0.9 (0.565)	-0.5 (0.565)
12:00 am	1.9 (0.577)	-0.5 (0.565)
3:00 am	0.2 (0.565)	-1.1 (0.570)
6:00 am	0.2 (0.571)	0.9 (0.565)

Adverse Events

Time Frame	Adverse events were collected for the duration of the study.
Adverse Event Reporting Description	The safety population is defined as patients who received study medication.
Arm/Group Title	AZARGA		COMBIGAN
Arm/Group Description	One drop in the study eye, twice daily (9:00 and 21:00), for six weeks		One drop in the study eye, twice daily (9:00 and 21:00), for six weeks
All Cause Mortality
	AZARGA		COMBIGAN
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	AZARGA		COMBIGAN
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/34 (2.9%)		0/34 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer	1/34 (2.9%)		0/34 (0%)
Other (Not Including Serious) Adverse Events
	AZARGA		COMBIGAN
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		0/34 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor reserves the right of prior review of any publication or presentation of information related to the study.