Fixed Combination Brinzolamide 1%/Timolol 0.5% Versus Brinzolamide 1% + Timolol 0.5% in Open-Angle Glaucoma or Ocular Hypertension

• Sponsor: Alcon Research (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01357616
• Collaborator: (none)
• Enrollment: 328
• Arms: 2
• Duration (Months): 26

Study Details

Study Description

Brief Summary

The purpose of this study was to compare the intraocular pressure (IOP)-lowering efficacy and safety of AZARGA™ (Brinzolamide 1%/Timolol 0.5% Ophthalmic Suspension), dosed twice daily versus AZOPT® (Brinzolamide 1% Ophthalmic Suspension) and Timolol 0.5% Ophthalmic Solution, each dosed twice daily, in Chinese patients with open-angle glaucoma or ocular hypertension who were insufficiently responsive to monotherapy.

Condition or Disease	Intervention/Treatment	Phase
Open-Angle Glaucoma; Ocular Hypertension	Drug: Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension; Drug: Brinzolamide 1% ophthalmic suspension; Drug: Timolol 0.5% ophthalmic solution	Phase 3

Detailed Description

The study consisted of 2 sequential phases. Phase I was the Screening/Eligibility Phase, with a Screening Visit followed by an Eligibility Visit. Phase II was the treatment phase and included Week 1, Week 2, Week 4, and Week 8 visits. Eligible subjects were randomized in a 1:1 ratio to receive Brinzolamide 1%/Timolol 0.5% or Brinzolamide 1% plus Timolol 0.5% two times a day for 8 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 328 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: Comparison of Efficacy and Safety of Brinzolamide/Timolol Fixed Combination (AZARGA™) vs Brinzolamide (AZOPT®) and Timolol in Chinese Subjects With Open-Angle Glaucoma or Ocular Hypertension
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AZARGA Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension, 1 drop in the affected eye(s) dosed twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.	Drug: Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension; Other Names: AZARGA™
Active Comparator: AZOPT + Timolol Brinzolamide 1% ophthalmic suspension, 1 drop instilled in the affected eye(s), followed by Timolol 0.5% ophthalmic solution, 1 drop instilled in the affected eye(s). Approximately 10 minutes separated the 2 instillations. The study drugs were instilled twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.	Drug: Brinzolamide 1% ophthalmic suspension; Other Names: AZOPT® ; Drug: Timolol 0.5% ophthalmic solution; Other Names: TIMOLOL

Outcome Measures

Primary Outcome Measures

1. Mean Diurnal IOP Change From Baseline at Week 8 [Baseline, Week 8]

   Mean diurnal IOP change from baseline at Week 8 (ie, the subject IOP change from baseline averaged over the 9 AM, 11AM and 5 PM time points at Week 8) was measured by Goldmann applanation tonometry. One eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. A higher IOP (fluid pressure inside the eye) can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates a greater improvement..

Secondary Outcome Measures

1. Mean IOP Change From Baseline at 9 AM [Baseline, Up to Week 8]

   Mean IOP change from baseline at 9 AM was measured by Goldmann applanation tonometry. One eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. A higher IOP (fluid pressure inside the eye) can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates a greater improvement.

2. Mean IOP Change From Baseline at 11 AM [Baseline, Up to Week 8]

   Mean IOP change from baseline at 11 AM was measured by Goldmann applanation tonometry. One eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. A higher IOP (fluid pressure inside the eye) can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates a greater improvement.

3. Mean IOP Change From Baseline (5 PM) at Week 8 [Baseline, Week 8]

   Mean IOP change from baseline (5 PM) at Week 8 was measured by Goldmann applanation tonometry. One eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. A higher IOP (fluid pressure inside the eye) can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates a greater improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosed with open angle glaucoma and/or ocular hypertension and not sufficiently responsive to monotherapy.

• Meet qualifying IOP criteria in at least 1 eye, including 21-35 mmHg at the Eligibility visit.

• Willing to sign an Informed Consent form.

• Contact lens wearer who is willing to remove lenses before instillation of study medication and wait a minimum of 15 minutes following drug instillation before re-inserting the lenses.

• Able to discontinue use of current IOP-lowering medications per the minimum washout period.

• Other protocol-specific inclusion criteria may apply.

Exclusion Criteria:

• Women of childbearing potential if pregnant, test positive for pregnancy at Screening/Enrollment visit, breastfeeding, or not in agreement to use adequate birth control methods to prevent pregnancy throughout the study.

• Diagnosed with any form of glaucoma other than open-angle glaucoma and/or ocular hypertension.

• Diagnosed with severe central visual field loss in either eye.

• History of chronic, recurrent, or severe ocular infection, inflammatory eye disease in either eye.

• History of ocular trauma within the past 6 months in either eye.

• Current ocular infection or ocular inflammation within the past 3 months in either eye.

• Ocular laser surgery within the past 3 months.

• Intraocular surgery within the past 3 months.

• Best-corrected visual acuity score worse than 55 ETDRS letters read (equivalent to approximately 20/80 Snellen, 0.60 logMAR or 0.25 decimal).

• History of, or current clinically relevant or progressive retinal disease in either eye.

• History of, or current other severe ocular pathology (including severe dry eye) in either eye, that would preclude the administration of a topical carbonic anhydrase inhibitor (CAI) or beta-blocker.

• Any abnormality preventing reliable applanation tonometry.

• History of, or current condition or disease that would preclude the safe administration of a topical beta blocker or topical beta-adrenergic blocking agent.

• History of spontaneous or current hypoglycemia or uncontrolled diabetes.

• History of severe or serious hypersensitivity to CAIs, beta-blockers, or to any components of the study medication.

• Less than 30 days stable dosing regimen before the Screening Visit of any medications or substances administered by any route and used on a chronic basis that may have affected IOP.

• Recent use of high-dose salicylate therapy.

• Anticipated use of any additional topical or systemic ocular hypotensive medication during the study.

• Not safely able to discontinue all glucocorticoid medications administered by any route.

• Currently on therapy or have been on therapy with another investigational agent within 30 days prior to the Screening Visit.

• History of, or current evidence of severe illness or any other conditions which would, in the opinion of the Investigator, make the subject unsuitable for the study.

• Other protocol-specific exclusion criteria may apply.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Alcon Research

Investigators

• Study Director: Mandy Ye, MS, Alcon Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alcon Research
• ClinicalTrials.gov Identifier: NCT01357616
• Other Study ID Numbers: C-08-076
• First Posted: May 20, 2011
• Last Update Posted: Apr 10, 2014
• Last Verified: Mar 1, 2014

• Keywords provided by Alcon Research: Glaucoma; Open-angle glaucoma; Ocular hypertension; OAG; OH
• Additional relevant MeSH terms: Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Timolol; Ophthalmic Solutions; Brinzolamide

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from 13 study centers located in China.
Pre-assignment Detail	This reporting group includes all enrolled subjects.

Arm/Group Title	AZARGA	AZOPT + TIMOLOL
Arm/Group Description	Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension, 1 drop in the affected eye(s) dosed twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.	Brinzolamide 1% ophthalmic suspension and Timolol 0.5% ophthalmic solution, 1 drop of each component instilled in the affected eye(s), waiting approximately 10 minutes between instillation of the 2 drops. Study drugs were instilled twice daily (9AM and 9PM) for 8 weeks.
Period Title: Overall Study
STARTED	166	162
COMPLETED	156	153
NOT COMPLETED	10	9

Baseline Characteristics

Arm/Group Title	AZARGA	AZOPT + TIMOLOL	Total
Arm/Group Description	Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension, 1 drop in the affected eye(s) dosed twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.	Brinzolamide 1% ophthalmic suspension and Timolol 0.5% ophthalmic solution, 1 drop of each component instilled in the affected eye(s), waiting approximately 10 minutes between instillation of the 2 drops. Study drugs were instilled twice daily (9AM and 9PM) for 8 weeks.	Total of all reporting groups
Overall Participants	157	155	312
Age, Customized (participants) [Number]
<65 Years	148 94.3%	135 87.1%	283 90.7%
≥65 Years	9 5.7%	20 12.9%	29 9.3%
Sex: Female, Male (Count of Participants)
Female	69 43.9%	72 46.5%	141 45.2%
Male	88 56.1%	83 53.5%	171 54.8%

Outcome Measures

1. Primary Outcome

Title	Mean Diurnal IOP Change From Baseline at Week 8
Description	Mean diurnal IOP change from baseline at Week 8 (ie, the subject IOP change from baseline averaged over the 9 AM, 11AM and 5 PM time points at Week 8) was measured by Goldmann applanation tonometry. One eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. A higher IOP (fluid pressure inside the eye) can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates a greater improvement..
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

This reporting group includes all subjects who received study medication, satisfied pre-randomization inclusion/exclusion criteria and completed at least 1 scheduled on-therapy study visit.

Arm/Group Title	AZARGA	AZOPT + Timolol
Arm/Group Description	Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension, 1 drop in the affected eye(s) dosed twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.	Brinzolamide 1% ophthalmic suspension, 1 drop instilled in the affected eye(s), followed by Timolol 0.5% ophthalmic solution, 1 drop instilled in the affected eye(s). Approximately 10 minutes separated the 2 instillations. The study drugs were instilled twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.
Measure Participants	157	155
Least Squares Mean (Standard Deviation) [millimeters mercury (mmHg)]	-6.84 (3.557)	-6.00 (2.934)

2. Secondary Outcome

Title	Mean IOP Change From Baseline at 9 AM
Description	Mean IOP change from baseline at 9 AM was measured by Goldmann applanation tonometry. One eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. A higher IOP (fluid pressure inside the eye) can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates a greater improvement.
Time Frame	Baseline, Up to Week 8

Outcome Measure Data

Analysis Population Description

This reporting group includes all subjects who received study medication, satisfied pre-randomization inclusion/exclusion criteria and completed at least 1 scheduled on-therapy study visit.

Arm/Group Title	AZARGA	AZOPT + Timolol
Arm/Group Description	Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension, 1 drop in the affected eye(s) dosed twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.	Brinzolamide 1% ophthalmic suspension, 1 drop instilled in the affected eye(s), followed by Timolol 0.5% ophthalmic solution, 1 drop instilled in the affected eye(s). Approximately 10 minutes separated the 2 instillations. The study drugs were instilled twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.
Measure Participants	157	155
Change from baseline at Week 2	-6.9 (3.62)	-6.5 (3.43)
Change from baseline at Week 4	-7.3 (3.42)	-6.4 (3.11)
Change from baseline at Week 8	-6.7 (3.97)	-6.2 (3.30)

3. Secondary Outcome

Title	Mean IOP Change From Baseline at 11 AM
Description	Mean IOP change from baseline at 11 AM was measured by Goldmann applanation tonometry. One eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. A higher IOP (fluid pressure inside the eye) can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates a greater improvement.
Time Frame	Baseline, Up to Week 8

Outcome Measure Data

Analysis Population Description

This reporting group includes all subjects who received study medication, satisfied pre-randomization inclusion/exclusion criteria and completed at least 1 scheduled on-therapy study visit.

Arm/Group Title	AZARGA	AZOPT + Timolol
Arm/Group Description	Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension, 1 drop in the affected eye(s) dosed twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.	Brinzolamide 1% ophthalmic suspension, 1 drop instilled in the affected eye(s), followed by Timolol 0.5% ophthalmic solution, 1 drop instilled in the affected eye(s). Approximately 10 minutes separated the 2 instillations. The study drugs were instilled twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.
Measure Participants	157	155
Change from baseline at Week 2	-7.5 (3.19)	-6.8 (3.07)
Change from baseline at Week 4	-7.6 (3.46)	-6.8 (3.06)
Change from baseline at Week 8	-7.4 (3.92)	-6.5 (3.57)

4. Secondary Outcome

Title	Mean IOP Change From Baseline (5 PM) at Week 8
Description	Mean IOP change from baseline (5 PM) at Week 8 was measured by Goldmann applanation tonometry. One eye from each subject was chosen as the study eye, and only data for the study eye were used for the efficacy analysis. A higher IOP (fluid pressure inside the eye) can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). A more negative change indicates a greater improvement.
Time Frame	Baseline, Week 8

Outcome Measure Data

Analysis Population Description

This reporting group includes all subjects who received study medication, satisfied pre-randomization inclusion/exclusion criteria and completed at least 1 scheduled on-therapy study visit.

Arm/Group Title	AZARGA	AZOPT + Timolol
Arm/Group Description	Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension, 1 drop in the affected eye(s) dosed twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.	Brinzolamide 1% ophthalmic suspension, 1 drop instilled in the affected eye(s), followed by Timolol 0.5% ophthalmic solution, 1 drop instilled in the affected eye(s). Approximately 10 minutes separated the 2 instillations. The study drugs were instilled twice daily (9AM and 9PM) for 8 weeks. Both eyes were dosed unless there was a potential safety issue to the patient in the opinion of the Investigator.
Measure Participants	157	155
Least Squares Mean (Standard Deviation) [mmHg]	-6.3 (3.99)	-5.1 (3.34)

Adverse Events

Time Frame	Adverse Events (AE) were collected for the duration of the study (2 years, 2 months). An AE was defined as any untoward medical occurrence in a subject who was administered a study treatment, regardless of causal relationship with the treatment.
Adverse Event Reporting Description	Of the 328 enrolled, 1 subject did not receive study medication. This reporting group includes all subjects who were randomized and received study medication (327). Reports of AEs were obtained through solicited and spontaneous comments from the study subjects, and through observations by the study Investigator as outlined in the study protocol.
Arm/Group Title	AZARGA (Test Group)		AZOPT + TIMOLOL (Control Group)
Arm/Group Description	Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension, 1 drop in the affected eye(s) dosed twice daily (9AM and 9PM) for 8 weeks. Brinzolamide 1% / Timolol 0.5% fixed combination ophthalmic suspension		Brinzolamide 1% ophthalmic suspension and Timolol 0.5% ophthalmic solution, 1 drop of each component instilled in the affected eye(s), waiting approximately 10 minutes between instillation of the 2 drops. Study drugs were instilled twice daily (9AM and 9PM) for 8 weeks. Brinzolamide 1% ophthalmic suspension and Timolol 0.5% ophthalmic solution
All Cause Mortality
	AZARGA (Test Group)		AZOPT + TIMOLOL (Control Group)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	AZARGA (Test Group)		AZOPT + TIMOLOL (Control Group)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/165 (0.6%)		0/162 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of thymus	1/165 (0.6%)	1	0/162 (0%)	0
Other (Not Including Serious) Adverse Events
	AZARGA (Test Group)		AZOPT + TIMOLOL (Control Group)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/165 (8.5%)		10/162 (6.2%)
Investigations
Heart rate decreased	14/165 (8.5%)		10/162 (6.2%)

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.