Open-angle Glaucoma, Ocular Hypertension
Conditions
Brief summary
The purpose of this study is to evaluate the additive intraocular pressure (IOP) lowering effect of Brinzolamide 1%/Brimonidine 0.2% (SIMBRINZA®) dosed twice daily (BID) when added to Travoprost 0.004%/Timolol 0.5% (DUOTRAV®) in subjects with open-angle glaucoma or ocular hypertension.
Detailed description
This study is divided into 2 sequential phases for a total of 5 visits. Phase I of the study is the open-labeled Screening/Eligibility Phase, which includes a Screening Visit followed by 2 Eligibility Visits. Phase II of the study is the randomized, double-masked Treatment Phase, which includes 2 on-therapy visits: Visit 4 (at Week 2) and Visit 5 (Week 6, Exit Visit).
Interventions
DRUGBrinzolamide/brimonidine vehicle
Inactive ingredients used as placebo comparator
DRUGTravoprost 0.004%/timolol 0.5% solution
1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for up to 10 days during the Screening/Eligibility Phase and 42 days during the Treatment Phase
Sponsors
Alcon Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of open-angle glaucoma (including pseudoexfoliation or pigment dispersion glaucoma) or ocular hypertension. * Currently on treatment with Travoprost 0.004%/Timolol 0.5% prescribed as approved in the country, on morning or evening dosing for at least 28 days prior to screening, and in the opinion of the Investigator may benefit from further IOP lowering. * Mean IOP measurements at both the Eligibility 1 and Eligibility 2 visits, in at least 1 eye (the same eye(s) ≥ 19 and ≤ 28 mmHg at 09:00 while on a Travoprost 0.004%/ Timolol 0.5% solution. * Able to understand and sign an informed consent form that has been approved by an Institutional Review Board/Ethics Committee. * Willing and able to attend all study visits.
Exclusion criteria
* Women of childbearing potential: not postmenopausal for at least 1 year or less than 6 weeks since sterilization, currently pregnant; have a positive result on the urine pregnancy test at Screening; intend to become pregnant during the study period; breast-feeding; or not in agreement to use adequate birth control methods to prevent pregnancy throughout the study. * Mean IOP \> 28 mmHg at any time point in either eye during the Screening/Eligibility Phase. * Any form of glaucoma other than open-angle glaucoma or ocular hypertension. * Severe central visual field loss in either eye. * Chronic, recurrent or severe inflammatory eye disease in either eye. * Ocular trauma in either eye within the past 6 months prior to the Screening visit. * Ocular infection or ocular inflammation in either eye within the past 3 months prior to the Screening visit. * Retinal degeneration, diabetic retinopathy, or retinal detachment in either eye. * Best-corrected visual acuity score worse than 55 ETDRS letters (equivalent to approximately 20/80 Snellen, 0.60 logMAR or 0.25 decimal) in either eye. * Other ocular pathology (including severe dry eye) in either eye that may, in the opinion of the Investigator, preclude the safe administration of any study medication. * Intraocular surgery in either eye within the past 6 months prior to the Screening visit. * Ocular laser surgery in either eye within the past 3 months prior to the Screening visit. * Any other condition including severe illness which would make the subject, in the opinion of the Investigator, unsuitable for the study. * Asthma, history of asthma, or severe chronic obstructive pulmonary disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Diurnal Intraocular Pressure (IOP) (Mean of Changes at 09:00 and 11:00 Time Points) at Week 6 | Baseline, Week 6 | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry. Diurnal IOP change was defined as the average of the two changes from baseline (timepoints 9 AM, 11 AM). A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) was used for the analyses. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Diurnal IOP at Week 6 | Week 6 | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry. Diurnal IOP was defined as the average of the two time points measured (9 AM, 11 AM). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Only one eye (study eye) was used for the analyses. |
| Mean Percentage Change From Baseline in Diurnal IOP at Week 6 | Baseline, Week 6 | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry. Diurnal IOP percentage change was defined as the average of the two changes from baseline (timepoints 9 AM, 11 AM). A more negative percentage change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) was used for the analyses. |
| Mean Change From Baseline in IOP (09:00, 11:00) at Week 6 | Baseline, Week 6 | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) was used for the analyses. |
| Mean Percentage Change From Baseline in IOP (09:00, 11:00) at Week 6 | Baseline, Week 6 | IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry. A more negative percentage change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) was used for the analyses. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from sites located in Argentina, Australia, Belgium, Chile, Columbia, Germany, Greece, Italy, Malaysia, Poland, Spain, Taiwan, and the United Kingdom.
Pre-assignment details
Of the 173 enrolled, 39 subjects were exited as screen failures prior to randomization. This reporting group includes all randomized subjects (134).
Participants by arm
| Arm | Count |
|---|---|
| Simbrinza + Duotrav Brinzolamide 1%/brimonidine tartrate 0.2% ophthalmic suspension, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00 hrs) plus travoprost 0.004%/timolol 0.5% solution, 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for 42 days (Treatment Phase) | 67 |
| Vehicle + Duotrav Brinzolamide/brimonidine vehicle, 1 drop instilled 2 times per day in affected eye(s) (09:00 and 21:00 hrs) plus travoprost 0.004%/timolol 0.5% solution, 1 drop instilled in the affected eye(s) daily in the morning (at 9:00) or in the evening (at 21:00) for 42 days (Treatment Phase) | 67 |
| Total | 134 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 0 |
Baseline characteristics
| Characteristic | Simbrinza + Duotrav | Vehicle + Duotrav | Total |
|---|---|---|---|
| Age, Continuous | 65.7 years STANDARD_DEVIATION 13.47 | 65.7 years STANDARD_DEVIATION 11.77 | 65.7 years STANDARD_DEVIATION 12.6 |
| Intraocular Pressure (IOP) | 21.6 mmHg STANDARD_DEVIATION 1.78 | 21.8 mmHg STANDARD_DEVIATION 1.9 | 21.7 mmHg STANDARD_DEVIATION 1.84 |
| Race/Ethnicity, Customized Asian | 6 Participants | 7 Participants | 13 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 9 Participants | 3 Participants | 12 Participants |
| Race/Ethnicity, Customized White | 50 Participants | 57 Participants | 107 Participants |
| Sex: Female, Male Female | 32 Participants | 41 Participants | 73 Participants |
| Sex: Female, Male Male | 35 Participants | 26 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 67 | 0 / 67 |
| other Total, other adverse events | 0 / 67 | 0 / 67 |
| serious Total, serious adverse events | 0 / 67 | 1 / 67 |
Outcome results
Primary
Mean Change From Baseline in Diurnal Intraocular Pressure (IOP) (Mean of Changes at 09:00 and 11:00 Time Points) at Week 6
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry. Diurnal IOP change was defined as the average of the two changes from baseline (timepoints 9 AM, 11 AM). A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) was used for the analyses.
Time frame: Baseline, Week 6
Population: Full Analysis Set. At each time point, only subjects with a value at both baseline and that time point are included in the calculation of change.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Simbrinza + Duotrav | Mean Change From Baseline in Diurnal Intraocular Pressure (IOP) (Mean of Changes at 09:00 and 11:00 Time Points) at Week 6 | -4.5 mmHg | Standard Deviation 2.69 |
| Vehicle + Duotrav | Mean Change From Baseline in Diurnal Intraocular Pressure (IOP) (Mean of Changes at 09:00 and 11:00 Time Points) at Week 6 | -2.4 mmHg | Standard Deviation 3.01 |
p-value: <0.00195% CI: [-2.8, -1.5]ANCOVA
Secondary
Mean Change From Baseline in IOP (09:00, 11:00) at Week 6
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry. A more negative change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) was used for the analyses.
Time frame: Baseline, Week 6
Population: Full Analysis Set. At each time point, only subjects with a value at both baseline and that time point are included in the calculation of change.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Simbrinza + Duotrav | Mean Change From Baseline in IOP (09:00, 11:00) at Week 6 | Baseline 9:00 Hr | 22.2 mmHg | Standard Deviation 1.84 |
| Simbrinza + Duotrav | Mean Change From Baseline in IOP (09:00, 11:00) at Week 6 | Change from Baseline 9:00 Hr | -4.4 mmHg | Standard Deviation 3.07 |
| Simbrinza + Duotrav | Mean Change From Baseline in IOP (09:00, 11:00) at Week 6 | Change from Baseline 11:00 Hr | -5.4 mmHg | Standard Deviation 2.84 |
| Simbrinza + Duotrav | Mean Change From Baseline in IOP (09:00, 11:00) at Week 6 | Baseline 11:00 Hr | 21.4 mmHg | Standard Deviation 1.93 |
| Vehicle + Duotrav | Mean Change From Baseline in IOP (09:00, 11:00) at Week 6 | Change from Baseline 11:00 Hr | -2.5 mmHg | Standard Deviation 2.98 |
| Vehicle + Duotrav | Mean Change From Baseline in IOP (09:00, 11:00) at Week 6 | Baseline 9:00 Hr | 22.5 mmHg | Standard Deviation 1.8 |
| Vehicle + Duotrav | Mean Change From Baseline in IOP (09:00, 11:00) at Week 6 | Baseline 11:00 Hr | 21.4 mmHg | Standard Deviation 2.26 |
| Vehicle + Duotrav | Mean Change From Baseline in IOP (09:00, 11:00) at Week 6 | Change from Baseline 9:00 Hr | -3.2 mmHg | Standard Deviation 3.4 |
Comparison: Change from Baseline in IOP at 9:00p-value: 0.02295% CI: [-2.5, -0.2]Repeated measures model
Comparison: Change from Baseline in IOP at 11:00p-value: <0.00195% CI: [-3.9, -1.9]Repeated measures model
Secondary
Mean Diurnal IOP at Week 6
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry. Diurnal IOP was defined as the average of the two time points measured (9 AM, 11 AM). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). Only one eye (study eye) was used for the analyses.
Time frame: Week 6
Population: Full Analysis Set with non-missing values
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Simbrinza + Duotrav | Mean Diurnal IOP at Week 6 | 17.1 mmHg | Standard Deviation 2.96 |
| Vehicle + Duotrav | Mean Diurnal IOP at Week 6 | 19.4 mmHg | Standard Deviation 3.45 |
p-value: <0.00195% CI: [-2.8, -1.5]ANCOVA
Secondary
Mean Percentage Change From Baseline in Diurnal IOP at Week 6
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry. Diurnal IOP percentage change was defined as the average of the two changes from baseline (timepoints 9 AM, 11 AM). A more negative percentage change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) was used for the analyses.
Time frame: Baseline, Week 6
Population: Full Analysis Set. At each time point, only subjects with a value at both baseline and that time point are included in the calculation of change.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Simbrinza + Duotrav | Mean Percentage Change From Baseline in Diurnal IOP at Week 6 | -20.7 percentage change | Standard Deviation 12 |
| Vehicle + Duotrav | Mean Percentage Change From Baseline in Diurnal IOP at Week 6 | -11.1 percentage change | Standard Deviation 13.86 |
p-value: <0.00195% CI: [-13.1, -6.9]ANCOVA
Secondary
Mean Percentage Change From Baseline in IOP (09:00, 11:00) at Week 6
IOP (fluid pressure inside the eye) was assessed using Goldmann applanation tonometry. A more negative percentage change from baseline indicates a greater improvement, i.e., a reduction of IOP. Only one eye (study eye) was used for the analyses.
Time frame: Baseline, Week 6
Population: Full Analysis Set. At each time point, only subjects with a value at both Baseline and that time point are included in the calculation of change.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Simbrinza + Duotrav | Mean Percentage Change From Baseline in IOP (09:00, 11:00) at Week 6 | Percent change at 9:00 Hr | -20.2 percentage change | Standard Deviation 13.56 |
| Simbrinza + Duotrav | Mean Percentage Change From Baseline in IOP (09:00, 11:00) at Week 6 | Percent change at 11:00 Hr | -25.0 percentage change | Standard Deviation 12.73 |
| Vehicle + Duotrav | Mean Percentage Change From Baseline in IOP (09:00, 11:00) at Week 6 | Percent change at 9:00 Hr | -14.1 percentage change | Standard Deviation 15.1 |
| Vehicle + Duotrav | Mean Percentage Change From Baseline in IOP (09:00, 11:00) at Week 6 | Percent change at 11:00 Hr | -11.7 percentage change | Standard Deviation 13.63 |
Comparison: Percentage Change from Baseline in IOP at 09:00p-value: 0.01895% CI: [-11.2, -1.1]Repeated measures model
Comparison: Percentage Change from Baseline in IOP at 11:00p-value: <0.00195% CI: [-17.8, -8.6]Repeated measures model