Brinzolamide/Brimonidine Twice a Day (BID) Fixed Combination (FC) vs Brinzolamide BID and Brimonidine BID in Patients With Open Angle Glaucoma or Ocular Hypertension

• Sponsor: Alcon Research (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01310777
• Collaborator: (none)
• Enrollment: 771
• Arms: 3
• Duration (Months): 20.1

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate the safety and efficacy of Brinzolamide/Brimonidine in lowering intraocular pressure (IOP) relative to each of its individual active components in patients with open-angle glaucoma or ocular hypertension.

Condition or Disease	Intervention/Treatment	Phase
Open-Angle Glaucoma; Ocular Hypertension	Drug: Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension; Drug: Brinzolamide 1% ophthalmic suspension; Drug: Brimonidine tartrate 0.2% ophthalmic solution	Phase 3

Detailed Description

This study consisted of 7 visits conducted during 2 sequential phases: the screening/eligibility phase, which included a screening visit and 2 eligibility visits, and a treatment phase, which included 4 on-therapy visits conducted at Week 2, Week 6, Month 3, and Month 6 (or early exit). Following washout of any IOP-lowering medication, subjects who met all inclusion/exclusion criteria at both eligibility visits and who had IOP measurements within the specified range during this period were randomized to 1 of 3 study drug groups: Brinz/Brim, Brinz, or Brim.

Study Design

• Study Type: Interventional
• Actual Enrollment: 771 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Safety and IOP-Lowering Efficacy of Brinzolamide 10 mg/mL/Brimonidine 2 mg/mL Fixed Combination Eye Drops, Suspension Compared to Brinzolamide 10 mg/mL Eye Drops, Suspension and Brimonidine 2 mg/mL Eye Drops, Solution in Patients With Open-Angle Glaucoma or Ocular Hypertension
• Study Start Date: May 1, 2011
• Actual Primary Completion Date: Jan 1, 2013
• Actual Study Completion Date: Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brinz/Brim Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled in each eye 2 times a day for 6 months	Drug: Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension
Active Comparator: Brinz Brinzolamide 1% ophthalmic suspension, 1 drop instilled in each eye 2 times a day for 6 months	Drug: Brinzolamide 1% ophthalmic suspension; Other Names: AZOPT™
Active Comparator: Brim Brimonidine tartrate 0.2% ophthalmic solution, 1 drop instilled in each eye 2 times a day for 6 months	Drug: Brimonidine tartrate 0.2% ophthalmic solution

Outcome Measures

Primary Outcome Measures

1. Mean Diurnal IOP Change From Baseline at Month 3 [Baseline (Day 1), Month 3]

   Mean Diurnal IOP Change from Baseline at Month 3 (ie, the subject IOP change from baseline averaged over the 9 AM, + 2 h, and + 7 h time points at Month 3) was measured by Goldmann applanation tonometry. The study drug was instilled approximately 15 minutes after conducting the 9AM IOP measurement. 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 can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage).

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 or ocular hypertension, and, in the opinion of the Investigator, are insufficiently controlled on monotherapy or are currently on multiple IOP-lowering medications.

• Meet qualifying IOP entry criteria.

• Able to understand and sign an informed consent form.

• Other protocol-specified inclusion criteria may apply.

Exclusion Criteria:

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

• Severe central visual field loss.

• Best corrected visual acuity (BCVA) score worse than 55 ETDRS letters (20/80 Snellen equivalent).

• 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.

• Other ocular pathology.

• Intraocular surgery within the 6 months prior to entry.

• Ocular laser surgery within the 3 months prior to entry.

• Any abnormality preventing reliable applanation tonometry.

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

• Recent use of high-dose (>1 gram daily) salicylate therapy.

• Recent, current, or anticipated treatment with any medication that augments adrenergic responses, or precludes use of an alpha-adrenergic agonist.

• Concurrent use of glucocorticoid medications administered by any route.

• Other protocol-specified exclusion crtieria may apply.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Alcon Research

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alcon Research
• ClinicalTrials.gov Identifier: NCT01310777
• Other Study ID Numbers: C-10-040; 2010-024512-34
• First Posted: Mar 9, 2011
• Last Update Posted: Mar 6, 2014
• Last Verified: Dec 1, 2013

• Keywords provided by Alcon Research: Open-Angle glaucoma; Ocular Hypertension; OAG; OHT
• 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 63 investigational centers in the Asia-Pacific region, the European Union, Latin America and Caribbean nations, and the United States.
Pre-assignment Detail	Of the 771 enrolled, 211 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 (560).

Arm/Group Title	Brinz/Brim	Brinz	Brim
Arm/Group Description	Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled in each eye 2 times a day for 6 months	Brinzolamide 1% ophthalmic suspension, 1 drop instilled in each eye 2 times a day for 6 months	Brimonidine tartrate 0.2% ophthalmic solution, 1 drop instilled in each eye 2 times a day for 6 months
Period Title: Overall Study
STARTED	193	192	175
COMPLETED	160	178	145
NOT COMPLETED	33	14	30

Baseline Characteristics

Arm/Group Title	Brinz/Brim	Brinz	Brim	Total
Arm/Group Description	Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled in each eye 2 times a day for 6 months	Brinzolamide 1% ophthalmic suspension, 1 drop instilled in each eye 2 times a day for 6 months	Brimonidine tartrate 0.2% ophthalmic solution, 1 drop instilled in each eye 2 times a day for 6 months	Total of all reporting groups
Overall Participants	193	192	175	560
Age, Customized (participants) [Number]
<65 years	91 47.2%	87 45.3%	79 45.1%	257 45.9%
≥65 years	102 52.8%	105 54.7%	96 54.9%	303 54.1%
Sex: Female, Male (Count of Participants)
Female	106 54.9%	102 53.1%	102 58.3%	310 55.4%
Male	87 45.1%	90 46.9%	73 41.7%	250 44.6%

Outcome Measures

1. Primary Outcome

Title	Mean Diurnal IOP Change From Baseline at Month 3
Description	Mean Diurnal IOP Change from Baseline at Month 3 (ie, the subject IOP change from baseline averaged over the 9 AM, + 2 h, and + 7 h time points at Month 3) was measured by Goldmann applanation tonometry. The study drug was instilled approximately 15 minutes after conducting the 9AM IOP measurement. 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 can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage).
Time Frame	Baseline (Day 1), Month 3

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) analysis set included all subjects who received study drug and completed 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, 1 drop instilled in each eye 2 times a day for 6 months	Brinzolamide 1% ophthalmic suspension, 1 drop instilled in each eye 2 times a day for 6 months	Brimonidine tartrate 0.2% ophthalmic solution, 1 drop instilled in each eye 2 times a day for 6 months
Measure Participants	176	182	161
Least Squares Mean (Standard Error) [millimeters of mercury (mmHg)]	-7.9 (0.22)	-6.5 (0.23)	-6.4 (0.24)

Adverse Events

Time Frame	Adverse events were collected for the duration of the study (1 year, 8 months). An AE was defined as any untoward medical occurrence in a subject who was administered a study medication, regardless of causal relationship with the medication.
Adverse Event Reporting Description	This reporting group includes all subjects exposed to study drug. 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	Brinz/Brim		Brinz		Brim
Arm/Group Description	Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled in each eye 2 times a day for 6 months		Brinzolamide 1% ophthalmic suspension, 1 drop instilled in each eye 2 times a day for 6 months		Brimonidine tartrate 0.2% ophthalmic solution, 1 drop instilled in each eye 2 times a day for 6 months
All Cause Mortality
	Brinz/Brim		Brinz		Brim
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Brinz/Brim		Brinz		Brim
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/193 (2.6%)		2/192 (1%)		3/175 (1.7%)
Eye disorders
Macular degeneration	0/193 (0%)		0/192 (0%)		1/175 (0.6%)
Hepatobiliary disorders
Cholelithiasis	1/193 (0.5%)		0/192 (0%)		0/175 (0%)
Cholecystitis	0/193 (0%)		1/192 (0.5%)		0/175 (0%)
Infections and infestations
Cellulitis	1/193 (0.5%)		0/192 (0%)		0/175 (0%)
Cystitis	0/193 (0%)		0/192 (0%)		1/175 (0.6%)
Injury, poisoning and procedural complications
Vascular pseudoaneurysm	1/193 (0.5%)		0/192 (0%)		0/175 (0%)
Concussion	0/193 (0%)		0/192 (0%)		1/175 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/193 (0.5%)		0/192 (0%)		0/175 (0%)
Cervix carcinoma	1/193 (0.5%)		0/192 (0%)		0/175 (0%)
Pancreatic carcinoma	1/193 (0.5%)		0/192 (0%)		0/175 (0%)
Renal cell carcinoma	1/193 (0.5%)		0/192 (0%)		0/175 (0%)
Nervous system disorders
Carotid artery occlusion	0/193 (0%)		0/192 (0%)		1/175 (0.6%)
Headache	0/193 (0%)		0/192 (0%)		1/175 (0.6%)
Renal and urinary disorders
Calculus urethral	0/193 (0%)		1/192 (0.5%)		0/175 (0%)
Other (Not Including Serious) Adverse Events
	Brinz/Brim		Brinz		Brim
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/193 (22.8%)		12/192 (6.3%)		18/175 (10.3%)
Eye disorders
Ocular hyperaemia	11/193 (5.7%)		3/192 (1.6%)		9/175 (5.1%)
Conjunctivitis	11/193 (5.7%)		2/192 (1%)		2/175 (1.1%)
Vision Blurred	11/193 (5.7%)		1/192 (0.5%)		3/175 (1.7%)
Eye Pain	11/193 (5.7%)		3/192 (1.6%)		0/175 (0%)
Gastrointestinal disorders
Dry Mouth	7/193 (3.6%)		2/192 (1%)		9/175 (5.1%)
Nervous system disorders
Dysgeusia	11/193 (5.7%)		4/192 (2.1%)		2/175 (1.1%)

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.