Efficacy and Safety Study of Brinzolamide 1%/Brimonidine 0.2% vs. Brinzolamide 1% and Brimonidine 0.2%

• Sponsor: Alcon Research (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01297517
• Collaborator: (none)
• Enrollment: 1,001
• Arms: 3
• Duration (Months): 12.9

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate the efficacy and safety of a fixed combination of Brinzolamide/Brimonidine in lowering intraocular pressure (IOP) relative to each of its individual active components in patients with open-angle glaucoma and/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 ophthalmic suspension, 1%; Drug: Brimonidine tartrate ophthalmic solution, 0.2%	Phase 3

Detailed Description

This study consisted of 6 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 3 on-therapy visits conducted at Week 2, Week 6, and Month 3. A washout period based on previous ocular medication preceded Eligibility Visit 1. Patients who met all inclusion/exclusion criteria at both eligibility visits were randomized (1:1:1) to receive treatment with 1 of 3 study drugs for 3 months. Study drug instillation began the morning after the second eligibility visit.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1001 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Three Month Efficacy and Safety Study of a Fixed Combination of Brinzolamide 1%/Brimonidine 0.2% Compared to Brinzolamide 1% and Brimonidine 0.2% All Dosed Three Times Daily in Patients With Open-Angle Glaucoma and/or Ocular Hypertension
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brinzolamide/Brimonidine Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, one drop instilled in each eye three times a day for 3 months	Drug: Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension
Active Comparator: Brinzolamide Brinzolamide ophthalmic suspension, 1%, one drop instilled in each eye three times a day for 3 months	Drug: Brinzolamide ophthalmic suspension, 1%; Other Names: AZOPT®
Active Comparator: Brimonidine Brimonidine tartrate ophthalmic solution, 0.2%, one drop instilled in each eye three times a day for 3 months	Drug: Brimonidine tartrate ophthalmic solution, 0.2%

Outcome Measures

Primary Outcome Measures

1. Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h) [Month 3]

   At the Month 3 (Exit) visit, the 8 am IOP measurement was taken before instillation of study drug. The study drug was instilled approximately 15 minutes after the 8 am measurement. An additional dose was given at 3 pm. 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).

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: NCT01297517
• Other Study ID Numbers: C-10-033
• First Posted: Feb 16, 2011
• Last Update Posted: May 21, 2013
• Last Verified: May 1, 2013

• Keywords provided by Alcon Research: AOG; OHT; Open-Angle Glaucoma; Ocular Hypertension
• 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 68 study centers in the US.
Pre-assignment Detail	Of the 1001 enrolled, 341 subjects did not qualify for treatment and were exited without exposure to product. The 660 subjects eligible for treatment were randomized (1:1:1) to study drug. This reporting group includes all randomized subjects, as treated.

Arm/Group Title	Brinzolamide/Brimonidine	Brinzolamide	Brimonidine
Arm/Group Description	Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Brinzolamide ophthalmic suspension, 1%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Brimonidine tartrate ophthalmic solution, 0.2%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months
Period Title: Overall Study
STARTED	214	226	220
COMPLETED	187	214	193
NOT COMPLETED	27	12	27

Baseline Characteristics

Arm/Group Title	Brinzolamide/Brimonidine	Brinzolamide	Brimonidine	Total
Arm/Group Description	Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Brinzolamide ophthalmic suspension, 1%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Brimonidine tartrate ophthalmic solution, 0.2%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Total of all reporting groups
Overall Participants	214	226	220	660
Age, Customized (participants) [Number]
18 to 64 years	107 50%	101 44.7%	117 53.2%	325 49.2%
≥65 years	107 50%	125 55.3%	103 46.8%	335 50.8%
Sex: Female, Male (Count of Participants)
Female	140 65.4%	128 56.6%	135 61.4%	403 61.1%
Male	74 34.6%	98 43.4%	85 38.6%	257 38.9%

Outcome Measures

1. Primary Outcome

Title	Mean IOP at Month 3 for Each Assessment Timepoint (8 AM, + 2 h, + 7 h, and + 9 h)
Description	At the Month 3 (Exit) visit, the 8 am IOP measurement was taken before instillation of study drug. The study drug was instilled approximately 15 minutes after the 8 am measurement. An additional dose was given at 3 pm. 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).
Time Frame	Month 3

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT): All patients who received study medication and completed at least 1 scheduled on-therapy study visit. Observed case analysis of the ITT dataset, per randomized treatment assignment.

Arm/Group Title	Brinzolamide/Brimonidine	Brinzolamide	Brimonidine
Arm/Group Description	Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Brinzolamide ophthalmic suspension, 1%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months	Brimonidine tartrate ophthalmic solution, 0.2%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months
Measure Participants	189	213	192
8 am (before study drug instillation)	20.5 (0.29)	21.6 (0.28)	23.3 (0.29)
+2 hrs relative to 8 am dosing	17.2 (0.29)	20.4 (0.28)	19.7 (0.29)
+7 hrs relative to 8 am dosing	18.7 (0.29)	20.4 (0.28)	21.3 (0.29)
+9 hrs relative to 8 am dosing	17.0 (0.29)	20.0 (0.28)	18.8 (0.29)

Adverse Events

Time Frame	Adverse events were collected for the duration of the study (1 year). An AE was any untoward medical occurrence in a patient administered a study medication, regardless of whether or not the event had a causal relationship with the medication.
Adverse Event Reporting Description	This reporting group includes all participants randomized to study drug, as treated. Adverse events were obtained as solicited comments from the study patients and as observations by the study investigator as outlined in the study protocol.
Arm/Group Title	Brinzolamide/Brimonidine		Brinzolamide		Brimonidine
Arm/Group Description	Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months		Brinzolamide ophthalmic suspension, 1%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months		Brimonidine tartrate ophthalmic solution, 0.2%, one drop instilled in each eye three times a day (8 am, 3 pm, 10 pm) for three months
All Cause Mortality
	Brinzolamide/Brimonidine		Brinzolamide		Brimonidine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Brinzolamide/Brimonidine		Brinzolamide		Brimonidine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/214 (0.9%)		6/226 (2.7%)		2/220 (0.9%)
Blood and lymphatic system disorders
Anaemia	0/214 (0%)		1/226 (0.4%)		0/220 (0%)
Cardiac disorders
Angina pectoris	0/214 (0%)		1/226 (0.4%)		0/220 (0%)
Ear and labyrinth disorders
Vertigo	1/214 (0.5%)		0/226 (0%)		0/220 (0%)
General disorders
Chest pain	0/214 (0%)		1/226 (0.4%)		0/220 (0%)
Chest pain	0/214 (0%)		0/226 (0%)		2/220 (0.9%)
Injury, poisoning and procedural complications
Collapse of lung	0/214 (0%)		1/226 (0.4%)		0/220 (0%)
Injury	0/214 (0%)		0/226 (0%)		1/220 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Vulval neoplasm	0/214 (0%)		1/226 (0.4%)		0/220 (0%)
Nervous system disorders
Amnesia	0/214 (0%)		1/226 (0.4%)		0/220 (0%)
Surgical and medical procedures
Cardiac pacemaker insertion	1/214 (0.5%)		0/226 (0%)		0/220 (0%)
Vertebroplasty	0/214 (0%)		1/226 (0.4%)		0/220 (0%)
Other (Not Including Serious) Adverse Events
	Brinzolamide/Brimonidine		Brinzolamide		Brimonidine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/214 (9.3%)		26/226 (11.5%)		1/220 (0.5%)
Eye disorders
Vision blurred	14/214 (6.5%)		15/226 (6.6%)		1/220 (0.5%)
Nervous system disorders
Dysgeusia	8/214 (3.7%)		14/226 (6.2%)		0/220 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.