Glaucoma, Open-Angle, Ocular Hypertension
Conditions
Brief summary
Phase III study to compare the safety and efficacy of intraocular implants containing Travoprost at two different elution rates versus Timolol Maleate Ophthalmic Solution, 0.5% (Timolol) in reducing elevated intraocular pressure in subjects with open angle glaucoma (OAG) or ocular hypertension (OHT)
Detailed description
This is a prospective, randomized, double-masked, active-controlled, parallel-group, multi-center trial comparing the efficacy and safety of the Model G2TR-063 Travoprost Intraocular Implant and the Model G2TR-125 Travoprost Intraocular Implant to topical Timolol in subjects with OAG or OHT. The staff who record key efficacy measures and the study subjects will remain masked to study treatment.
Interventions
COMBINATION_PRODUCTG2-TR intraocular implant containing travoprost
Provided in Arm/Group descriptions
Sham surgery plus postoperative active-comparator eye drops (Timolol Maleate ophthalmic solution, 0.5%)
Sponsors
Glaukos Corporation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with open-angle glaucoma or ocular hypertension * C/D ratio ≤ 0.8 * Zero to two preoperative ocular hypotensive medications
Exclusion criteria
* Active corneal inflammation or edema * Retinal disorders not associated with glaucoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative | 3 Months | Change from time-matched baseline in IOP at 8AM and 10AM at Day 10, Week 6 and Month 3. Day 10 8AM IOP minus Baseline 8AM IOP; Day 10 10AM IOP minus Baseline 10AM IOP; Week 6 8AM IOP minus Baseline 8AM IOP; Week 6 10AM IOP minus Baseline 10AM IOP; Month 3 8AM IOP minus Baseline 8AM IOP; Month 3 10AM IOP minus Baseline 10AM IOP. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean IOP (Control Group vs. Each Implant Group) Through 12 Months Postoperative | 12 Months | Difference in mean IOP, between each test group and the control group, for IOP measurements through the Month 12 follow-up visit |
Countries
United States
Participant flow
Pre-assignment details
subjects required to undergo washout of prior IOP-lowering medication(s) if applicable and to meet inclusion/exclusion criteria
Participants by arm
| Arm | Count |
|---|---|
| Implant Group 1 G2-TR intraocular implant containing Travoprost 75 mcg with high elution rate, plus postoperative placebo eye drops.
G2-TR intraocular implant containing travoprost: Provided in Arm/Group descriptions | 185 |
| Implant Group 2 G2-TR intraocular implant containing Travoprost 75 mcg with low elution rate, plus postoperative placebo eye drops.
G2-TR intraocular implant containing travoprost: Provided in Arm/Group descriptions | 183 |
| Control Group Sham surgery + active-comparator eye drops
Sham surgery + active-comparator eye drops: Sham surgery plus postoperative active-comparator eye drops (Timolol Maleate ophthalmic solution, 0.5%) | 192 |
| Total | 560 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 3 |
| Overall Study | Death | 1 | 1 | 2 |
| Overall Study | Explanted | 2 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 2 |
| Overall Study | Ongoing in study | 176 | 180 | 183 |
| Overall Study | Physician Decision | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 0 | 1 |
Baseline characteristics
| Characteristic | Implant Group 1 | Implant Group 2 | Control Group | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 93 Participants | 83 Participants | 99 Participants | 275 Participants |
| Age, Categorical Between 18 and 65 years | 92 Participants | 100 Participants | 93 Participants | 285 Participants |
| Age, Continuous | 63.1 years STANDARD_DEVIATION 11.8 | 61.9 years STANDARD_DEVIATION 12.8 | 63.9 years STANDARD_DEVIATION 12.1 | 63.0 years STANDARD_DEVIATION 12.2 |
| Baseline Mean Diurnal IOP | 24.4 mmHg STANDARD_DEVIATION 3.21 | 24.1 mmHg STANDARD_DEVIATION 2.81 | 24.3 mmHg STANDARD_DEVIATION 2.99 | 24.3 mmHg STANDARD_DEVIATION 3 |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants | 2 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 26 Participants | 22 Participants | 20 Participants | 68 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 2 Participants | 5 Participants | 11 Participants |
| Race (NIH/OMB) White | 150 Participants | 155 Participants | 162 Participants | 467 Participants |
| Region of Enrollment Armenia | 17 participants | 16 participants | 17 participants | 50 participants |
| Region of Enrollment United States | 168 participants | 167 participants | 175 participants | 510 participants |
| Sex: Female, Male Female | 88 Participants | 88 Participants | 105 Participants | 281 Participants |
| Sex: Female, Male Male | 97 Participants | 95 Participants | 87 Participants | 279 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 185 | 1 / 183 | 2 / 192 |
| other Total, other adverse events | 20 / 185 | 23 / 183 | 7 / 192 |
| serious Total, serious adverse events | 6 / 185 | 4 / 183 | 2 / 192 |
Outcome results
Primary
Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative
Change from time-matched baseline in IOP at 8AM and 10AM at Day 10, Week 6 and Month 3. Day 10 8AM IOP minus Baseline 8AM IOP; Day 10 10AM IOP minus Baseline 10AM IOP; Week 6 8AM IOP minus Baseline 8AM IOP; Week 6 10AM IOP minus Baseline 10AM IOP; Month 3 8AM IOP minus Baseline 8AM IOP; Month 3 10AM IOP minus Baseline 10AM IOP.
Time frame: 3 Months
Population: intent to treatment analysis set which includes all randomized subjects with analyses performed according to original treatment assignment, regardless of actual treatment received
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Implant Group 1 | Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative | Day 10, 8AM | -8.26 mmHg | Standard Error 0.27 |
| Implant Group 1 | Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative | Day 10, 10AM | -8.20 mmHg | Standard Error 0.25 |
| Implant Group 1 | Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative | Week 6, 8AM | -6.83 mmHg | Standard Error 0.26 |
| Implant Group 1 | Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative | Week 6, 10AM | -6.92 mmHg | Standard Error 0.25 |
| Implant Group 1 | Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative | Month 3, 8AM | -6.29 mmHg | Standard Error 0.28 |
| Implant Group 1 | Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative | Month 3, 10AM | -6.21 mmHg | Standard Error 0.27 |
| Implant Group 2 | Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative | Month 3, 10AM | -6.79 mmHg | Standard Error 0.27 |
| Implant Group 2 | Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative | Day 10, 8AM | -8.40 mmHg | Standard Error 0.27 |
| Implant Group 2 | Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative | Week 6, 10AM | -6.83 mmHg | Standard Error 0.25 |
| Implant Group 2 | Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative | Month 3, 8AM | -6.66 mmHg | Standard Error 0.27 |
| Implant Group 2 | Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative | Day 10, 10AM | -8.28 mmHg | Standard Error 0.25 |
| Implant Group 2 | Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative | Week 6, 8AM | -7.20 mmHg | Standard Error 0.26 |
| Control Group | Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative | Day 10, 10AM | -7.08 mmHg | Standard Error 0.24 |
| Control Group | Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative | Week 6, 8AM | -7.17 mmHg | Standard Error 0.26 |
| Control Group | Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative | Month 3, 10AM | -6.76 mmHg | Standard Error 0.26 |
| Control Group | Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative | Week 6, 10AM | -7.15 mmHg | Standard Error 0.25 |
| Control Group | Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative | Day 10, 8AM | -7.16 mmHg | Standard Error 0.26 |
| Control Group | Change From Baseline in Diurnal IOP (as Measured at 8AM and 10AM) Through 3 Months Postoperative | Month 3, 8AM | -6.82 mmHg | Standard Error 0.27 |
Comparison: Day 10, 8AM Difference between Implant Group 2 and timolol~Note: Multiple imputation techniques were used to account for missing data such that the sample size at each visit /timepoint was the same for purposes of statistical analyses95% CI: [-1.99, -0.5]
Comparison: Month 3, 10AM Difference between Implant Group 2 and timolol~Note: Multiple imputation techniques were used to account for missing data such that the sample size at each visit /timepoint was the same for purposes of statistical analyses95% CI: [-1.88, -0.52]
Comparison: Week 6, 8AM Difference between Implant Group 2 and timolol~Note: Multiple imputation techniques were used to account for missing data such that the sample size at each visit /timepoint was the same for purposes of statistical analyses95% CI: [-0.76, 0.69]
Comparison: Week 6, 10AM Difference between Implant Group 2 and Timolol~Note: Multiple imputation techniques were used to account for missing data such that the sample size at each visit /timepoint was the same for purposes of statistical analyses95% CI: [-0.37, 1.01]
Comparison: Month 3, 8AM Difference between Implant Group 2 and timolol~Note: Multiple imputation techniques were used to account for missing data such that the sample size at each visit /timepoint was the same for purposes of statistical analyses95% CI: [-0.59, 0.91]
Comparison: Month 3, 10AM Difference between Implant Group 2 and timolol~Note: Multiple imputation techniques were used to account for missing data such that the sample size at each visit /timepoint was the same for purposes of statistical analyses95% CI: [-0.77, 0.71]
Comparison: Day 10, 8AM Difference between Implant Group 1 vs. Timolol~Note: Multiple imputation techniques were used to account for missing data such that the sample size at each visit /timepoint was the same for purposes of statistical analyses95% CI: [-1.84, -0.36]
Comparison: Day 10, 10AM Difference between Implant Group 1 vs. Timolol~Note: Multiple imputation techniques were used to account for missing data such that the sample size at each visit /timepoint was the same for purposes of statistical analyses95% CI: [-1.81, -0.45]
Comparison: Week 6, 8AM Difference between Implant Group 1 vs. Timolol~Note: Multiple imputation techniques were used to account for missing data such that the sample size at each visit /timepoint was the same for purposes of statistical analyses95% CI: [-0.39, 1.06]
Comparison: Week 6, 10AM Difference between Implant Group 1 vs. Timolol~Note: Multiple imputation techniques were used to account for missing data such that the sample size at each visit /timepoint was the same for purposes of statistical analyses95% CI: [-0.46, 0.93]
Comparison: Month 3, 8AM Difference between Implant Group 1 and Timolol~Note: Multiple imputation techniques were used to account for missing data such that the sample size at each visit /timepoint was the same for purposes of statistical analyses95% CI: [-0.23, 1.28]
Comparison: Month 3, 10AM Difference between Implant Group 1 and Timolol~Note: Multiple imputation techniques were used to account for missing data such that the sample size at each visit /timepoint was the same for purposes of statistical analyses95% CI: [-0.19, 1.29]
Secondary
Mean IOP (Control Group vs. Each Implant Group) Through 12 Months Postoperative
Difference in mean IOP, between each test group and the control group, for IOP measurements through the Month 12 follow-up visit
Time frame: 12 Months