Safety and Efficacy of Brinzolamide/Brimonidine Fixed Combination

• ClinicalTrials.gov Identifier: NCT00961649
• Recruitment Status: Terminated
• First Posted: August 19, 2009
• Results First Posted: July 4, 2013
• Last Update Posted: July 4, 2013
• Sponsor: Alcon Research
• Information provided by (Responsible Party): Alcon Research

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 (Clinical Trial)
• 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: October 2009
• Actual Primary Completion Date: February 2010
• Actual Study Completion Date: February 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 [ Time Frame: 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 [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Sponsors and Collaborators

Alcon Research

Investigators

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

More Information

• Responsible Party: Alcon Research
• ClinicalTrials.gov Identifier: NCT00961649
• Other Study ID Numbers: C-09-038
• First Posted: August 19, 2009
• Results First Posted: July 4, 2013
• Last Update Posted: July 4, 2013
• Last Verified: May 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; Vascular Diseases; Cardiovascular Diseases; Eye Diseases; Brimonidine Tartrate; Ophthalmic Solutions; Brinzolamide; Pharmaceutical Solutions; Antihypertensive Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Carbonic Anhydrase Inhibitors; Enzyme Inhibitors