Safety and Efficacy of Brinzolamide/Brimonidine Fixed Combination

• Sponsor: Alcon Research (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00961649
• Collaborator: (none)
• Enrollment: 195
• Arms: 4
• Duration (Months): 4

Study Details

Study Description

Brief Summary

The purpose of this study was to compare the safety and intraocular pressure (IOP)-lowering efficacy of a new fixed combination of brinzolamide/brimonidine (Brinz/Brim) to:

• its individual components (Brinz and Brim), and

• the concomitant administration of Brinz and Brim (Brinz+Brim).

Condition or Disease	Intervention/Treatment	Phase
Open-Angle Glaucoma; Ocular Hypertension	Drug: Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension; Drug: Brinzolamide ophthalmic suspension, 1%; Drug: Brimonidine tartrate ophthalmic solution, 0.2%; Other: Vehicle	Phase 2

Detailed Description

This study consisted of 5 visits conducted during 2 sequential phases: the screening/eligibility phase, which included a screening visit and 2 eligibility visits, and the treatment phase, which included 2 on-therapy visits conducted at Week 2 and Week 6 (or early exit). A washout period based on previous ocular medication preceded Eligibility Visit

1. Subjects who met all inclusion/exclusion criteria at both eligibility visits were randomized to 1 of 4 study drug groups for 6 weeks. Study drug instillation began the morning after the second eligibility visit. The study was terminated by the sponsor out of caution due to microgel formation in the Brinz/Brim formulation. 13 remaining active subjects were discontinued. Further analysis revealed that neither the drop size nor the concentration of the active ingredients was affected.

Study Design

• Study Type: Interventional
• Actual Enrollment: 195 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Safety and IOP-Lowering Efficacy of Brinzolamide/Brimonidine Fixed Combination Ophthalmic Suspension in Patients With Open-Angle Glaucoma and/or Ocular Hypertension
• Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brinz/Brim Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks. A time lapse of at least 10 minutes was required between instillations of each study drug.	Drug: Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension; Other: Vehicle; Inactive ingredients used as placebo
Active Comparator: Brinz Brinzolamide ophthalmic suspension, 1% and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks. A time lapse of at least 10 minutes was required between instillations of each study drug.	Drug: Brinzolamide ophthalmic suspension, 1%; Other: Vehicle; Inactive ingredients used as placebo
Active Comparator: Brim Brimonidine tartrate ophthalmic solution, 0.2% and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks. A time lapse of at least 10 minutes was required between instillations of each study drug.	Drug: Brimonidine tartrate ophthalmic solution, 0.2%; Other: Vehicle; Inactive ingredients used as placebo
Active Comparator: Brinz+Brim Brinzolamide ophthalmic suspension, 1% and brimonidine tartrate ophthalmic solution, 0.2%: 1 drop each instilled in both eyes 3 times a day for 6 weeks. A time lapse of at least 10 minutes was required between instillations of each study drug.	Drug: Brinzolamide ophthalmic suspension, 1%; Drug: Brimonidine tartrate ophthalmic solution, 0.2%

Outcome Measures

Primary Outcome Measures

1. Mean Change in Intraocular Pressure (IOP) From Baseline to Each of the Assessment Time Points (8 AM, + 2 Hrs, + 7 Hrs, and + 9 Hrs) at Week 6 - Brinz/Brim, Brinz, Brim [Baseline, Week 6]

   The study drug was instilled at 8 AM and +7 hours relative to the 8 AM dosing (approximately 15 minutes after conducting the IOP measurements). Intraocular pressure was measured by Goldmann applanation tonometry. One eye from each patient was chosen as the study eye and only data for the study eye were used for the efficacy analysis. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Intent-to-Treat (ITT) analysis data set was pre-specified for the comparison of Brinz/Brim to its individual components (Brinz and Brim).

2. Mean Change in Intraocular Pressure (IOP) From Baseline to Each of the Assessment Time Points (8 AM, +2 Hrs, +7 Hrs, and +9 Hrs) at Week 6 - Brinz/Brim, Brinz+Brim [Baseline, Week 6]

   The study drug was instilled at 8 AM and +7 hours relative to the 8 AM dosing (approximately 15 minutes after conducting the IOP measurements). Intraocular pressure was measured by Goldmann applanation tonometry. One eye from each patient was chosen as the study eye and only data for the study eye were used for the efficacy analysis. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Per-Protocol (PP) analysis data set was pre-specified for the comparison of Brinz/Brim to Brinz+Brim.

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 document.

• Diagnosis of open-angle glaucoma or ocular hypertension, with mean intraocular pressure within protocol-specified range at eligibility visit/s.

• Other protocol-specified inclusion criteria may apply.

Exclusion Criteria:

• Females of childbearing potential if pregnant, lactating, or not using highly effective birth control measures.

• Any form of glaucoma other than open-angle glaucoma.

• Severe central vision loss in either eye.

• Chronic, recurrent, or severe inflammatory eye disease.

• Ocular trauma within the preceding 6 months.

• Ocular infection or ocular inflammation within the preceding 3 months.

• Clinically significant or progressive retinal disease such as retinal degeneration, diabetic retinopathy, or retinal detachment.

• Best-corrected visual acuity score worse than 55 letters using the Early Treatment Diabetic Retinopathy Study chart.

• Other ocular pathology (including severe dry eye) that may, in the opinion of the Investigator, preclude the administration of study product.

• Ocular surgery within the preceding 6 months.

• Ocular laser surgery within the preceding 3 months.

• Any abnormality preventing reliable applanation tonometry.

• Any other conditions, including severe illness, which could make the patient, in the opinion of the Investigator, unsuitable for the study.

• Other protocol-specified exclusion criteria may apply.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Alcon Research

Investigators

• Study Director: James Teague, BS, Sr. Clinical Manager, Alcon Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alcon Research
• ClinicalTrials.gov Identifier: NCT00961649
• Other Study ID Numbers: C-09-038
• First Posted: Aug 19, 2009
• Last Update Posted: Jul 4, 2013
• Last Verified: May 1, 2013

• Keywords provided by Alcon Research: Open-Angle Glaucoma; Ocular Hypertension; Brinzolamide; Brimonidine; Intraocular Pressure
• Additional relevant MeSH terms: Glaucoma; Glaucoma, Open-Angle; Ocular Hypertension; Hypertension; Brimonidine Tartrate; Ophthalmic Solutions; Brinzolamide

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from 9 investigational centers in the United States.
Pre-assignment Detail	Of the 195 enrolled, 25 subjects did not meet inclusion/exclusion criteria and were exited from the study as screen failures prior to randomization. This reporting group includes all randomized subjects (170).

Arm/Group Title	Brinz/Brim	Brinz+Brim	Brinz	Brim
Arm/Group Description	Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks	Brinzolamide ophthalmic suspension, 1% and brimonidine tartrate ophthalmic solution, 0.2%: 1 drop each instilled in both eyes 3 times a day for 6 weeks	Brinzolamide ophthalmic suspension, 1% and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks	Brimonidine tartrate ophthalmic solution, 0.2% and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks
Period Title: Overall Study
STARTED	41	44	44	41
COMPLETED	32	40	39	37
NOT COMPLETED	9	4	5	4

Baseline Characteristics

Arm/Group Title	Brinz/Brim	Brinz+Brim	Brinz	Brim	Total
Arm/Group Description	Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks	Brinzolamide ophthalmic suspension, 1% and brimonidine tartrate ophthalmic solution, 0.2%: 1 drop each instilled in both eyes 3 times a day for 6 weeks	Brinzolamide ophthalmic suspension, 1% and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks	Brimonidine tartrate ophthalmic solution, 0.2% and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks	Total of all reporting groups
Overall Participants	41	44	44	41	170
Age, Customized (participants) [Number]
18 to 64 years	15 36.6%	20 45.5%	20 45.5%	21 51.2%	76 44.7%
≥65 years	26 63.4%	24 54.5%	24 54.5%	20 48.8%	94 55.3%
Sex: Female, Male (Count of Participants)
Female	23 56.1%	22 50%	26 59.1%	25 61%	96 56.5%
Male	18 43.9%	22 50%	18 40.9%	16 39%	74 43.5%
Region of Enrollment (participants) [Number]
United States	41 100%	44 100%	44 100%	41 100%	170 100%

Outcome Measures

1. Primary Outcome

Title	Mean Change in Intraocular Pressure (IOP) From Baseline to Each of the Assessment Time Points (8 AM, + 2 Hrs, + 7 Hrs, and + 9 Hrs) at Week 6 - Brinz/Brim, Brinz, Brim
Description	The study drug was instilled at 8 AM and +7 hours relative to the 8 AM dosing (approximately 15 minutes after conducting the IOP measurements). Intraocular pressure was measured by Goldmann applanation tonometry. One eye from each patient was chosen as the study eye and only data for the study eye were used for the efficacy analysis. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Intent-to-Treat (ITT) analysis data set was pre-specified for the comparison of Brinz/Brim to its individual components (Brinz and Brim).
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

ITT: All subjects who received study drug and had at least 1 scheduled on-therapy study visit.

Arm/Group Title	Brinz/Brim	Brinz	Brim
Arm/Group Description	Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks	Brinzolamide ophthalmic suspension, 1% and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks	Brimonidine tartrate ophthalmic solution, 0.2% and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks
Measure Participants	41	44	41
Change from Baseline (BL) at 8 AM	-5.5 (0.51)	-5.7 (0.48)	-4.1 (0.50)
Change from BL at +2 hours relative to 8 AM dosing	-8.5 (0.51)	-4.7 (0.48)	-5.3 (0.51)
Change from BL at +7 hours relative to 8 AM dosing	-5.4 (0.51)	-2.8 (0.48)	-3.0 (0.51)
Change from BL at +9 hours relative to 8 AM dosing	-6.8 (0.51)	-3.9 (0.48)	-5.9 (0.51)

2. Primary Outcome

Title	Mean Change in Intraocular Pressure (IOP) From Baseline to Each of the Assessment Time Points (8 AM, +2 Hrs, +7 Hrs, and +9 Hrs) at Week 6 - Brinz/Brim, Brinz+Brim
Description	The study drug was instilled at 8 AM and +7 hours relative to the 8 AM dosing (approximately 15 minutes after conducting the IOP measurements). Intraocular pressure was measured by Goldmann applanation tonometry. One eye from each patient was chosen as the study eye and only data for the study eye were used for the efficacy analysis. A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Per-Protocol (PP) analysis data set was pre-specified for the comparison of Brinz/Brim to Brinz+Brim.
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

PP: All subjects who received study drug, satisfied inclusion/exclusion criteria, and had at least 1 scheduled on-therapy visit. Individual subject visits or data points were excluded if protocol criteria were violated at a subset of the subject's visits and the violations, in the opinion of the Medical Monitor, did not invalidate remaining visits.

Arm/Group Title	Brinz/Brim	Brinz+Brim
Arm/Group Description	Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks	Brinzolamide ophthalmic suspension, 1% and brimonidine tartrate ophthalmic solution, 0.2%: 1 drop each instilled in both eyes 3 times a day for 6 weeks
Measure Participants	38	41
Change from Baseline (BL) at 8 AM	-5.5 (0.52)	-5.7 (0.50)
Change from BL at +2 hours relative to 8 AM dosing	-8.4 (0.54)	-8.3 (0.52)
Change from BL at +7 hours relative to 8 AM dosing	-5.0 (0.54)	-4.4 (0.52)
Change from BL at +9 hours relative to 8 AM dosing	-6.3 (0.55)	-6.3 (0.53)

Adverse Events

Time Frame	Adverse events were collected for the duration of the study. The safety population includes all subjects who were exposed to the study medications.
Adverse Event Reporting Description	An adverse event was defined as any untoward medical occurrence in a subject who was administered a study treatment regardless of whether or not the event had a causal relationship with the treatment. All AEs were obtained as solicited comments from the study subjects and as observations by the Investigator as outlined in the study protocol.
Arm/Group Title	Brinz/Brim		Brinz+Brim		Brinz		Brim
Arm/Group Description	Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks		Brinzolamide ophthalmic suspension, 1% and brimonidine tartrate ophthalmic solution, 0.2%: 1 drop each instilled in both eyes 3 times a day for 6 weeks		Brinzolamide ophthalmic suspension, 1% and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks		Brimonidine tartrate ophthalmic solution, 0.2% and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks
All Cause Mortality
	Brinz/Brim		Brinz+Brim		Brinz		Brim
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Brinz/Brim		Brinz+Brim		Brinz		Brim
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/41 (2.4%)		1/44 (2.3%)		0/44 (0%)		0/41 (0%)
Gastrointestinal disorders
Abdominal pain	1/41 (2.4%)		0/44 (0%)		0/44 (0%)		0/41 (0%)
General disorders
Chest pain	0/41 (0%)		1/44 (2.3%)		0/44 (0%)		0/41 (0%)
Hepatobiliary disorders
Cholecystitis	1/41 (2.4%)		0/44 (0%)		0/44 (0%)		0/41 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/41 (0%)		1/44 (2.3%)		0/44 (0%)		0/41 (0%)
Other (Not Including Serious) Adverse Events
	Brinz/Brim		Brinz+Brim		Brinz		Brim
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/41 (24.4%)		8/44 (18.2%)		9/44 (20.5%)		7/41 (17.1%)
Eye disorders
Vision blurred	7/41 (17.1%)		6/44 (13.6%)		7/44 (15.9%)		6/41 (14.6%)
Ocular hyperaemia	3/41 (7.3%)		0/44 (0%)		2/44 (4.5%)		1/41 (2.4%)
Eye pain	0/41 (0%)		3/44 (6.8%)		2/44 (4.5%)		0/41 (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.