Glaucoma, Open-Angle, Ocular Hypertension
Conditions
Brief summary
This study will evaluate the safety and efficacy of Triple Combination Therapy compared with Fixed Combination brimonidine tartrate/timolol ophthalmic solution in patients with primary open-angle glaucoma or ocular hypertension.
Interventions
One drop of Triple Combination Therapy administered to each eye, twice daily for up to 12 months.
One drop of Fixed Combination 0.2% brimonidine tartrate/0.5% timolol ophthalmic solution administered to each eye, twice daily for up to 12 months.
Sponsors
Allergan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ocular hypertension or primary open-angle glaucoma in each eye * Requires treatment with IOP-lowering medication in both eyes
Exclusion criteria
* Required chronic use of ocular medications during the study other than study medication * Use of any corticosteroids within 30 days * History of any traumatic eye surgeries * Cataract surgery in the past 6 months * Anticipated wearing of contact lenses during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Two-Sample T-Test | Baseline, Week 12 | Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. IOP is evaluated at Hour 0 and Hour 2 in the worse eye, defined as the eye with the worse (higher) Hour 0 IOP at baseline. The mean of Hours 0 and 2 is calculated at Baseline and Week 12 in the worse eye. A negative number change from baseline indicates a reduction in IOP (improvement) and a positive number change from baseline indicates an increase in IOP (worsening). Data are analyzed using a two-sample t-test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Month 6, Month 9, Month 12 | Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. IOP is evaluated at Hour 0 and Hour 2 in the worse eye, defined as the eye with the worse (higher) Hour 0 IOP at baseline. The mean of Hours 0 and 2 is calculated at Baseline and Week 12 in the worse eye. A negative number change from baseline indicates a reduction in IOP (improvement) and a positive number change from baseline indicates an increase in IOP (worsening). Data are analyzed by a mixed-effect model for repeated measure. |
| Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) | Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Month 6, Month 9, Month 12 | Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. IOP is evaluated at Hour 0 and Hour 2 in the worse eye, defined as the eye with the worse (higher) IOP at baseline. The mean of Hours 0 and 2 is calculated at Baseline and Week 12 in the worse eye. A negative number change from baseline indicates a reduction in IOP (improvement) and a positive number change from baseline indicates an increase in IOP (worsening). Data are analyzed by ANCOVA. |
Countries
Brazil
Participant flow
Pre-assignment details
Patients were randomized into a 12-week Initial Treatment phase. Following this phase, patients may have continued into the 9-month Masked Extension on the same treatment assignment.
Participants by arm
| Arm | Count |
|---|---|
| Triple Combination Therapy Triple Combination Therapy with bimatoprost/brimonidine tartrate/timolol ophthalmic solution. One drop of Triple Combination Therapy administered to each eye, twice daily for up to 12 months. | 90 |
| Combigan® Fixed Combination brimonidine tartrate/timolol ophthalmic solution (Combigan®). One drop of Fixed Combination 0.2% brimonidine tartrate/0.5% timolol ophthalmic solution administered to each eye, twice daily for up to 12 months. | 95 |
| Total | 185 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 9-Month Masked Extension | Adverse Event | 3 | 6 |
| 9-Month Masked Extension | Lack of Efficacy | 2 | 0 |
| 9-Month Masked Extension | Lost to Follow-up | 1 | 0 |
| 9-Month Masked Extension | Other Reasons | 4 | 4 |
| 9-Month Masked Extension | Personal Reasons | 2 | 1 |
| 9-Month Masked Extension | Pregnancy | 1 | 0 |
| Initial Treatment Phase | Adverse Event | 10 | 6 |
| Initial Treatment Phase | Lack of Efficacy | 1 | 0 |
| Initial Treatment Phase | Other Reasons | 0 | 2 |
| Initial Treatment Phase | Personal Reasons | 0 | 2 |
| Initial Treatment Phase | Protocol Violation | 3 | 2 |
Baseline characteristics
| Characteristic | Triple Combination Therapy | Combigan® | Total |
|---|---|---|---|
| Age, Customized ≤65 years | 68 Participants | 62 Participants | 130 Participants |
| Age, Customized >65 years | 22 Participants | 33 Participants | 55 Participants |
| Gender Female | 53 Participants | 63 Participants | 116 Participants |
| Gender Male | 37 Participants | 32 Participants | 69 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 84 / 90 | 77 / 95 |
| serious Total, serious adverse events | 1 / 90 | 1 / 95 |
Outcome results
Primary
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Two-Sample T-Test
Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. IOP is evaluated at Hour 0 and Hour 2 in the worse eye, defined as the eye with the worse (higher) Hour 0 IOP at baseline. The mean of Hours 0 and 2 is calculated at Baseline and Week 12 in the worse eye. A negative number change from baseline indicates a reduction in IOP (improvement) and a positive number change from baseline indicates an increase in IOP (worsening). Data are analyzed using a two-sample t-test.
Time frame: Baseline, Week 12
Population: Modified Intent to Treat: all randomized patients with at least one post-baseline efficacy evaluation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Two-Sample T-Test | Baseline | 25.42 Millimeters of Mercury (mmHg) | Standard Deviation 2.902 |
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Two-Sample T-Test | Change from Baseline at Week 12 (N=85, 93) | -10.45 Millimeters of Mercury (mmHg) | Standard Deviation 3.175 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Two-Sample T-Test | Baseline | 24.43 Millimeters of Mercury (mmHg) | Standard Deviation 2.592 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Two-Sample T-Test | Change from Baseline at Week 12 (N=85, 93) | -8.28 Millimeters of Mercury (mmHg) | Standard Deviation 3.256 |
Secondary
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA)
Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. IOP is evaluated at Hour 0 and Hour 2 in the worse eye, defined as the eye with the worse (higher) IOP at baseline. The mean of Hours 0 and 2 is calculated at Baseline and Week 12 in the worse eye. A negative number change from baseline indicates a reduction in IOP (improvement) and a positive number change from baseline indicates an increase in IOP (worsening). Data are analyzed by ANCOVA.
Time frame: Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Month 6, Month 9, Month 12
Population: Modified Intent to Treat: all randomized patients with at least one post-baseline efficacy evaluation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) | Change from Baseline at Week 1 (N=82, 91) | -11.63 Millimeters of Mercury (mmHg) | Standard Deviation 3.06 |
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) | Change from Baseline at Week 12 (N=85, 93) | -10.45 Millimeters of Mercury (mmHg) | Standard Deviation 3.175 |
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) | Change from Baseline at Week 4 (N=85, 93) | -10.85 Millimeters of Mercury (mmHg) | Standard Deviation 3.18 |
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) | Change from Baseline at Month 6 (N=67, 73) | -10.32 Millimeters of Mercury (mmHg) | Standard Deviation 2.965 |
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) | Change from Baseline at Week 2 (N=84, 92) | -11.20 Millimeters of Mercury (mmHg) | Standard Deviation 3.29 |
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) | Change from Baseline at Month 9 (N=67, 73) | -10.09 Millimeters of Mercury (mmHg) | Standard Deviation 3.349 |
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) | Change from Baseline at Week 8 (N=85, 93) | -10.44 Millimeters of Mercury (mmHg) | Standard Deviation 3.105 |
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) | Change from Baseline at Month 12 (N=67, 73) | -9.36 Millimeters of Mercury (mmHg) | Standard Deviation 3.368 |
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) | Baseline | 25.42 Millimeters of Mercury (mmHg) | Standard Deviation 2.902 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) | Change from Baseline at Month 12 (N=67, 73) | -7.77 Millimeters of Mercury (mmHg) | Standard Deviation 3.489 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) | Baseline | 24.43 Millimeters of Mercury (mmHg) | Standard Deviation 2.592 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) | Change from Baseline at Week 1 (N=82, 91) | -8.13 Millimeters of Mercury (mmHg) | Standard Deviation 2.969 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) | Change from Baseline at Week 2 (N=84, 92) | -8.28 Millimeters of Mercury (mmHg) | Standard Deviation 3.076 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) | Change from Baseline at Week 4 (N=85, 93) | -8.53 Millimeters of Mercury (mmHg) | Standard Deviation 3.228 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) | Change from Baseline at Week 8 (N=85, 93) | -8.07 Millimeters of Mercury (mmHg) | Standard Deviation 3.521 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) | Change from Baseline at Week 12 (N=85, 93) | -8.28 Millimeters of Mercury (mmHg) | Standard Deviation 3.256 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) | Change from Baseline at Month 6 (N=67, 73) | -8.42 Millimeters of Mercury (mmHg) | Standard Deviation 3.252 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Analysis of Covariance (ANCOVA) | Change from Baseline at Month 9 (N=67, 73) | -8.17 Millimeters of Mercury (mmHg) | Standard Deviation 3.031 |
Secondary
Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure
Intraocular pressure (IOP) is a measurement of the fluid pressure inside the eye. IOP is evaluated at Hour 0 and Hour 2 in the worse eye, defined as the eye with the worse (higher) Hour 0 IOP at baseline. The mean of Hours 0 and 2 is calculated at Baseline and Week 12 in the worse eye. A negative number change from baseline indicates a reduction in IOP (improvement) and a positive number change from baseline indicates an increase in IOP (worsening). Data are analyzed by a mixed-effect model for repeated measure.
Time frame: Baseline, Week 1, Week 2, Week 4, Week 8, Week 12, Month 6, Month 9, Month 12
Population: Modified Intent to Treat: all randomized patients with at least one post-baseline efficacy evaluation and who have data at the noted time point (no missing imputation)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure | Change from Baseline at Week 1 (N=82, 91) | -11.63 Millimeters of Mercury (mmHg) | Standard Deviation 3.06 |
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure | Change from Baseline at Week 12 (N=76, 83) | -10.56 Millimeters of Mercury (mmHg) | Standard Deviation 3.224 |
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure | Change from Baseline at Week 4 (N=82, 88) | -10.88 Millimeters of Mercury (mmHg) | Standard Deviation 3.193 |
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure | Change from Baseline at Month 6 (N=64, 69) | -10.41 Millimeters of Mercury (mmHg) | Standard Deviation 2.976 |
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure | Change from Baseline at Week 2 (N=82, 87) | -11.24 Millimeters of Mercury (mmHg) | Standard Deviation 3.283 |
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure | Change from Baseline at Month 9 (N=58, 67) | -10.29 Millimeters of Mercury (mmHg) | Standard Deviation 3.275 |
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure | Change from Baseline at Week 8 (N=75, 87) | -10.53 Millimeters of Mercury (mmHg) | Standard Deviation 3.165 |
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure | Change from Baseline at Month 12 (N=55, 63) | -9.38 Millimeters of Mercury (mmHg) | Standard Deviation 3.398 |
| Triple Combination Therapy | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure | Baseline | 25.42 Millimeters of Mercury (mmHg) | Standard Deviation 2.902 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure | Change from Baseline at Month 12 (N=55, 63) | -7.58 Millimeters of Mercury (mmHg) | Standard Deviation 3.486 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure | Baseline | 24.43 Millimeters of Mercury (mmHg) | Standard Deviation 2.592 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure | Change from Baseline at Week 1 (N=82, 91) | -8.13 Millimeters of Mercury (mmHg) | Standard Deviation 2.969 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure | Change from Baseline at Week 2 (N=82, 87) | -8.12 Millimeters of Mercury (mmHg) | Standard Deviation 2.942 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure | Change from Baseline at Week 4 (N=82, 88) | -8.35 Millimeters of Mercury (mmHg) | Standard Deviation 3.1 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure | Change from Baseline at Week 8 (N=75, 87) | -7.94 Millimeters of Mercury (mmHg) | Standard Deviation 3.453 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure | Change from Baseline at Week 12 (N=76, 83) | -8.16 Millimeters of Mercury (mmHg) | Standard Deviation 3.161 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure | Change from Baseline at Month 6 (N=64, 69) | -8.29 Millimeters of Mercury (mmHg) | Standard Deviation 3.221 |
| Combigan® | Change From Baseline in Mean Worse Eye Intraocular Pressure (IOP) Analyzed by Mixed-Effect Model for Repeated Measure | Change from Baseline at Month 9 (N=58, 67) | -8.14 Millimeters of Mercury (mmHg) | Standard Deviation 2.937 |