Open-Angle Glaucoma, Ocular Hypertension
Conditions
Keywords
Open-Angle Glaucoma, Ocular Hypertension, Brinzolamide, Brimonidine, Intraocular Pressure
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).
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.
Interventions
OTHERVehicle
Inactive ingredients used as placebo
Sponsors
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
Participant flow
Recruitment details
Subjects were recruited from 9 investigational centers in the United States.
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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 | 41 |
| 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 | 44 |
| Brinz Brinzolamide ophthalmic suspension, 1% and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks | 44 |
| Brim Brimonidine tartrate ophthalmic solution, 0.2% and Vehicle: 1 drop each instilled in both eyes 3 times a day for 6 weeks | 41 |
| Total | 170 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 | 0 | 2 |
| Overall Study | Inadequate control of IOP | 0 | 0 | 0 | 1 |
| Overall Study | Patient has travel plans during holidays | 0 | 0 | 1 | 0 |
| Overall Study | Patient left to Mexico-family emergency | 1 | 0 | 0 | 0 |
| Overall Study | Study terminated by sponsor | 4 | 4 | 4 | 1 |
Baseline characteristics
| Characteristic | Brinz/Brim | Brinz+Brim | Brinz | Brim | Total |
|---|---|---|---|---|---|
| Age, Customized 18 to 64 years | 15 participants | 20 participants | 20 participants | 21 participants | 76 participants |
| Age, Customized ≥65 years | 26 participants | 24 participants | 24 participants | 20 participants | 94 participants |
| Region of Enrollment United States | 41 participants | 44 participants | 44 participants | 41 participants | 170 participants |
| Sex: Female, Male Female | 23 Participants | 22 Participants | 26 Participants | 25 Participants | 96 Participants |
| Sex: Female, Male Male | 18 Participants | 22 Participants | 18 Participants | 16 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 10 / 41 | 8 / 44 | 9 / 44 | 7 / 41 |
| serious Total, serious adverse events | 1 / 41 | 1 / 44 | 0 / 44 | 0 / 41 |
Outcome results
Primary
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
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
Population: ITT: All subjects who received study drug and had at least 1 scheduled on-therapy study visit.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brinz/Brim | 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 | Change from Baseline (BL) at 8 AM | -5.5 millimeters mercury (mmHg) | Standard Error 0.51 |
| Brinz/Brim | 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 | Change from BL at +2 hours relative to 8 AM dosing | -8.5 millimeters mercury (mmHg) | Standard Error 0.51 |
| Brinz/Brim | 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 | Change from BL at +7 hours relative to 8 AM dosing | -5.4 millimeters mercury (mmHg) | Standard Error 0.51 |
| Brinz/Brim | 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 | Change from BL at +9 hours relative to 8 AM dosing | -6.8 millimeters mercury (mmHg) | Standard Error 0.51 |
| Brinz | 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 | Change from BL at +9 hours relative to 8 AM dosing | -3.9 millimeters mercury (mmHg) | Standard Error 0.48 |
| Brinz | 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 | Change from Baseline (BL) at 8 AM | -5.7 millimeters mercury (mmHg) | Standard Error 0.48 |
| Brinz | 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 | Change from BL at +7 hours relative to 8 AM dosing | -2.8 millimeters mercury (mmHg) | Standard Error 0.48 |
| Brinz | 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 | Change from BL at +2 hours relative to 8 AM dosing | -4.7 millimeters mercury (mmHg) | Standard Error 0.48 |
| Brim | 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 | Change from BL at +9 hours relative to 8 AM dosing | -5.9 millimeters mercury (mmHg) | Standard Error 0.51 |
| Brim | 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 | Change from BL at +2 hours relative to 8 AM dosing | -5.3 millimeters mercury (mmHg) | Standard Error 0.51 |
| Brim | 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 | Change from BL at +7 hours relative to 8 AM dosing | -3.0 millimeters mercury (mmHg) | Standard Error 0.51 |
| Brim | 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 | Change from Baseline (BL) at 8 AM | -4.1 millimeters mercury (mmHg) | Standard Error 0.5 |
Primary
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
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
Population: 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 | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Brinz/Brim | 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 | Change from Baseline (BL) at 8 AM | -5.5 millimeters mercury (mmHg) | Standard Error 0.52 |
| Brinz/Brim | 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 | Change from BL at +2 hours relative to 8 AM dosing | -8.4 millimeters mercury (mmHg) | Standard Error 0.54 |
| Brinz/Brim | 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 | Change from BL at +7 hours relative to 8 AM dosing | -5.0 millimeters mercury (mmHg) | Standard Error 0.54 |
| Brinz/Brim | 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 | Change from BL at +9 hours relative to 8 AM dosing | -6.3 millimeters mercury (mmHg) | Standard Error 0.55 |
| Brinz | 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 | Change from BL at +9 hours relative to 8 AM dosing | -6.3 millimeters mercury (mmHg) | Standard Error 0.53 |
| Brinz | 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 | Change from Baseline (BL) at 8 AM | -5.7 millimeters mercury (mmHg) | Standard Error 0.5 |
| Brinz | 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 | Change from BL at +7 hours relative to 8 AM dosing | -4.4 millimeters mercury (mmHg) | Standard Error 0.52 |
| Brinz | 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 | Change from BL at +2 hours relative to 8 AM dosing | -8.3 millimeters mercury (mmHg) | Standard Error 0.52 |