Three Month Efficacy/Safety Study With a 3-Month Safety Extension of Brinzolamide 1%/Brimonidine 0.2% vs. Brinzolamide 1% or Brimonidine 0.2%
Study Details
Study Description
Brief Summary
The purpose of this study was to evaluate the safety and efficacy of a new ophthalmic suspension (Brinz/Brim) in lowering intraocular pressure (IOP) relative to its individual active components in subjects with open-angle glaucoma and/or ocular hypertension.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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 the treatment phase, which included 4 on-therapy visits conducted at Week 2, Week 6, Month 3, and Month 6. A washout period based on previous ocular medication preceded Eligibility Visit
- Subjects who met all inclusion/exclusion criteria at both eligibility visits were randomized to 1 of 3 study drug groups. The study was designed to evaluate the efficacy and safety of Brinzolamide/Brimonidine over a 3-month period, with an additional 3 months of study drug exposure intended to provide further safety data.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Brinz/Brim Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled in each eye 3 times a day for 3 months |
Drug: Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension
|
| Active Comparator: Brinzolamide Brinzolamide ophthalmic suspension, 1%, 1 drop instilled in each eye 3 times a day for 3 months |
Drug: Brinzolamide ophthalmic suspension, 1%
|
| Active Comparator: Brimonidine Brimonidine tartrate ophthalmic solution, 0.2%, 1 drop instilled in each eye 3 times a day for 3 months |
Drug: Brimonidine tartrate ophthalmic solution, 0.2%
|
Outcome Measures
Primary Outcome Measures
- Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3 [Month 3]
The study drug was instilled at 8 AM and 3 PM (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).
Eligibility Criteria
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 subject, 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.- C-10-039
Study Results
Participant Flow
| Recruitment Details | Subjects were recruited and enrolled from 64 investigational centers in the United States. |
|---|---|
| Pre-assignment Detail | Of the 1062 enrolled, 372 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 (690), as treated. |
| Arm/Group Title | Brinz/Brim | Brinzolamide | Brimonidine |
|---|---|---|---|
| Arm/Group Description | Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled in each eye 3 times a day for 3 months | Brinzolamide ophthalmic suspension, 1%, 1 drop instilled in each eye 3 times a day for 3 months | Brimonidine tartrate ophthalmic solution, 0.2%, 1 drop instilled in each eye 3 times a day for 3 months |
| Period Title: Overall Study | |||
| STARTED | 221 | 234 | 235 |
| COMPLETED | 163 | 207 | 178 |
| NOT COMPLETED | 58 | 27 | 57 |
Baseline Characteristics
| Arm/Group Title | Brinz/Brim | Brinzolamide | Brimonidine | Total |
|---|---|---|---|---|
| Arm/Group Description | Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled in each eye 3 times a day for 3 months | Brinzolamide ophthalmic suspension, 1%, 1 drop instilled in each eye 3 times a day for 3 months | Brimonidine tartrate ophthalmic solution, 0.2%, 1 drop instilled in each eye 3 times a day for 3 months | Total of all reporting groups |
| Overall Participants | 221 | 234 | 235 | 690 |
| Age, Customized (participants) [Number] | ||||
| 18 to 64 years |
99
44.8%
|
113
48.3%
|
115
48.9%
|
327
47.4%
|
| ≥65 years |
122
55.2%
|
121
51.7%
|
120
51.1%
|
363
52.6%
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
119
53.8%
|
136
58.1%
|
132
56.2%
|
387
56.1%
|
| Male |
102
46.2%
|
98
41.9%
|
103
43.8%
|
303
43.9%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
221
100%
|
234
100%
|
235
100%
|
690
100%
|
Outcome Measures
| Title | Mean Intraocular Pressure (IOP) at Each Assessment Timepoint (8 AM, +2 h, +7 h, and +9 h) at Month 3 |
|---|---|
| Description | The study drug was instilled at 8 AM and 3 PM (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). |
| Time Frame | Month 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat (ITT): All subjects 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 | Brinz/Brim | Brinzolamide | Brimonidine |
|---|---|---|---|
| Arm/Group Description | Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled in each eye 3 times a day for 3 months | Brinzolamide ophthalmic suspension, 1%, 1 drop instilled in each eye 3 times a day for 3 months | Brimonidine tartrate ophthalmic solution, 0.2%, 1 drop instilled in each eye 3 times a day for 3 months |
| Measure Participants | 196 | 216 | 203 |
| 8 AM (before study drug instillation) |
21.1
(0.30)
|
22.0
(0.29)
|
23.2
(0.30)
|
| + 2 hours relative to 8 AM dosing |
18.0
(0.30)
|
20.8
(0.29)
|
19.9
(0.30)
|
| + 7 hours relative to 8 AM dosing |
19.5
(0.30)
|
20.7
(0.29)
|
21.5
(0.30)
|
| + 9 hours relative to 8 AM dosing |
17.2
(0.30)
|
20.4
(0.29)
|
18.9
(0.30)
|
Adverse Events
| Time Frame | Adverse events were collected for the duration of the study. The safety population includes all subjects who were exposed to study drug. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | An adverse event was any untoward medical occurrence in a subject exposed to study drug. The AE did not necessarily have to have had a causal relationship with the study drug. Reports of AEs were obtained through solicited and spontaneous comments from the subjects and through observations by the Investigator as outlined in the study protocol. | |||||
| Arm/Group Title | Brinz/Brim | Brinzolamide | Brimonidine | |||
| Arm/Group Description | Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled in each eye 3 times a day for 3 months | Brinzolamide ophthalmic suspension, 1%, 1 drop instilled in each eye 3 times a day for 3 months | Brimonidine tartrate ophthalmic solution, 0.2%, 1 drop instilled in each eye 3 times a day for 3 months | |||
All Cause Mortality |
||||||
| Brinz/Brim | Brinzolamide | Brimonidine | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Brinz/Brim | Brinzolamide | Brimonidine | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/221 (3.2%) | 7/234 (3%) | 7/235 (3%) | |||
| Cardiac disorders | ||||||
| Atrial fibrillation | 0/221 (0%) | 0/234 (0%) | 1/235 (0.4%) | |||
| Ear and labyrinth disorders | ||||||
| Vertigo | 0/221 (0%) | 1/234 (0.4%) | 0/235 (0%) | |||
| Eye disorders | ||||||
| Retinal detachment | 1/221 (0.5%) | 0/234 (0%) | 0/235 (0%) | |||
| Retinal tear | 1/221 (0.5%) | 0/234 (0%) | 0/235 (0%) | |||
| General disorders | ||||||
| Chest pain | 1/221 (0.5%) | 0/234 (0%) | 0/235 (0%) | |||
| Asthenia | 0/221 (0%) | 0/234 (0%) | 1/235 (0.4%) | |||
| Hepatobiliary disorders | ||||||
| Cholecystitis | 0/221 (0%) | 1/234 (0.4%) | 0/235 (0%) | |||
| Immune system disorders | ||||||
| Anaphylactic reaction | 1/221 (0.5%) | 0/234 (0%) | 0/235 (0%) | |||
| Infections and infestations | ||||||
| Abdominal abscess | 1/221 (0.5%) | 0/234 (0%) | 0/235 (0%) | |||
| Appendicitis | 1/221 (0.5%) | 0/234 (0%) | 0/235 (0%) | |||
| Bronchitis | 1/221 (0.5%) | 0/234 (0%) | 0/235 (0%) | |||
| Pneumonia | 1/221 (0.5%) | 0/234 (0%) | 0/235 (0%) | |||
| Otitis media chronic | 0/221 (0%) | 0/234 (0%) | 1/235 (0.4%) | |||
| Injury, poisoning and procedural complications | ||||||
| Injury | 1/221 (0.5%) | 0/234 (0%) | 0/235 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Osteoarthritis | 0/221 (0%) | 0/234 (0%) | 1/235 (0.4%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Pancreatic carcinoma | 0/221 (0%) | 1/234 (0.4%) | 0/235 (0%) | |||
| Nervous system disorders | ||||||
| Amnesia | 0/221 (0%) | 1/234 (0.4%) | 0/235 (0%) | |||
| Psychiatric disorders | ||||||
| Delirium | 0/221 (0%) | 1/234 (0.4%) | 0/235 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Endometrial hyperplasia | 0/221 (0%) | 1/234 (0.4%) | 0/235 (0%) | |||
| Benign prostatic hyperplasia | 0/221 (0%) | 0/234 (0%) | 1/235 (0.4%) | |||
| Prostatitis | 0/221 (0%) | 0/234 (0%) | 1/235 (0.4%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Pulmonary embolism | 0/221 (0%) | 0/234 (0%) | 1/235 (0.4%) | |||
| Surgical and medical procedures | ||||||
| Aortic aneurysm repair | 1/221 (0.5%) | 0/234 (0%) | 0/235 (0%) | |||
| Nephrectomy | 1/221 (0.5%) | 0/234 (0%) | 0/235 (0%) | |||
| Prostatectomy | 1/221 (0.5%) | 0/234 (0%) | 0/235 (0%) | |||
| Intervertebral disc operation | 0/221 (0%) | 1/234 (0.4%) | 0/235 (0%) | |||
| Knee arthroplasty | 0/221 (0%) | 0/234 (0%) | 1/235 (0.4%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Brinz/Brim | Brinzolamide | Brimonidine | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 53/221 (24%) | 35/234 (15%) | 27/235 (11.5%) | |||
| Eye disorders | ||||||
| Conjunctivitis | 16/221 (7.2%) | 0/234 (0%) | 15/235 (6.4%) | |||
| Vision blurred | 12/221 (5.4%) | 18/234 (7.7%) | 1/235 (0.4%) | |||
| Eye allergy | 14/221 (6.3%) | 1/234 (0.4%) | 5/235 (2.1%) | |||
| Eye irritation | 14/221 (6.3%) | 6/234 (2.6%) | 9/235 (3.8%) | |||
| Nervous system disorders | ||||||
| Dysgeusia | 9/221 (4.1%) | 24/234 (10.3%) | 2/235 (0.9%) | |||
Limitations/Caveats
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.
Results Point of Contact
| Name/Title | Matt Walker, PhD, Clinical Project Lead |
|---|---|
| Organization | Alcon Research, Ltd. |
| Phone | 1-888-451-3937 |
| alcon.medinfo@alcon.com |
- C-10-039