Glaucoma, Primary Open Angle, Ocular Hypertension
Conditions
Keywords
POAG, OHT, Primary open-angle glaucoma, ocular hypertension
Brief summary
The study evaluated the safety and IOP-lowering effects of WB007 in adults with primary open-angle glaucoma or ocular hypertension in both eyes. This was a 2-part study. Part 1 was a 3-period dose escalation that evaluated 3 concentrations of WB007 ophthalmic solution following a single dose in one eye. Part 2 was a randomized, double-masked, parallel comparison that evaluated two concentrations of WB007 (selected based on Part 1 results) in both eyes compared with timolol 0.5% for 14 days.
Interventions
DRUGTimolol 0.5%
Timolol Maleate 0.5% Ophthalmic Solution
DRUGWB007 0.05%
WB007 Ophthalmic Solution 0.05%
DRUGWB007 0.15%
WB007 Ophthalmic Solution 0.15%
DRUGWB007 0.4%
WB007 Ophthalmic Solution 0.4%
Sponsors
Bausch & Lomb Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Part 1 - not masked; Part 2 - Double-masked - neither investigator, study staff nor study participant were aware of treatment assignment
Intervention model description
Part 1 - Open-labelled, single dose, 3-period dose escalation; Part 2 - Double-masked, randomized, parallel comparison
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
Exclusion criteria
* History of orthostatic hypotension * Any active ocular disease * Anticipated wearing of contact lenses during study * Contraindication to pupil dilatation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Baseline, Day 14 | IOP is a measurement of the pressure inside the eye and was measured using Goldmann applanation tonometry. Study participants used the study medications in both eyes for 14 days. One eye was designated as the Study Eye at baseline: eyes that met inclusion and exclusion criteria. If both eyes were eligible, the study eye was the eye with higher IOP at Baseline at Hour 0. If both eyes had the same IOP at this timepoint, the right eye was designated as the study eye. IOP was measured at Baseline and Day 14 at Hours 0, 2, 4 and 8. The primary endpoint was the mean change from baseline IOP at Day 14, Hour 2, the timepoint of the peak effect of timolol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Mean IOP at Day 14 - Study Eye | Baseline, Day 14 | IOP is a measurement of the pressure inside the eye and was measured using Goldmann applanation tonometry. Study participants used the study medications in both eyes for 14 days. One eye was designated as the Study Eye at baseline: eyes that met inclusion and exclusion criteria. If both eyes were eligible, the study eye was the eye with higher IOP at Baseline at Hour 0. If both eyes had the same IOP at this timepoint, the right eye was designated as the study eye. IOP was measured at Baseline and Day 14 at Hours 0, 2, 4 and 8. The primary timepoint was at Day 14, Hour 2, the timepoint of the peak effect of timolol. |
Countries
United States
Participant flow
Pre-assignment details
This was a 2-part study: Part 1: 18 subjects were enrolled and completed study. Based on results from Part 1, two WB007 doses were selected for Part 2. Part 2: 59 subjects were enrolled and completed the study. No subjects discontinued the study.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 (Period 1): WB007 0.05% WB007 0.05%, single dose to study eye on Day 1 | 6 |
| Part 1 (Period 2): WB007 0.15% WB007 0.15%, single dose to study eye on Day 1 | 6 |
| Part 1 (Period 3): WB007 0.4% WB007 0.4%, single dose to study eye on Day 1 | 6 |
| Part 2: WB007 0.15% WB007 0.15% dosed twice daily for 14 days | 23 |
| Part 2: WB007 0.4% WB007 0.4% dosed twice daily for 14 days | 24 |
| Part 2: Timolol 0.5% Timolol 0.5%, dosed twice daily for 14 days | 12 |
| Total | 77 |
Baseline characteristics
| Characteristic | Part 1 (Period 1): WB007 0.05% | Part 1 (Period 2): WB007 0.15% | Part 1 (Period 3): WB007 0.4% | Part 2: WB007 0.15% | Part 2: WB007 0.4% | Part 2: Timolol 0.5% | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 63.5 years STANDARD_DEVIATION 12.44 | 71.2 years STANDARD_DEVIATION 4.79 | 77.5 years STANDARD_DEVIATION 4.85 | 69.5 years STANDARD_DEVIATION 12.88 | 69.0 years STANDARD_DEVIATION 13.4 | 64.8 years STANDARD_DEVIATION 13.37 | 68.8 years STANDARD_DEVIATION 12.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 6 Participants | 7 Participants | 1 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 6 Participants | 6 Participants | 17 Participants | 17 Participants | 11 Participants | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 6 participants | 6 participants | 6 participants | 23 participants | 24 participants | 12 participants | 77 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 2 Participants | 14 Participants | 15 Participants | 7 Participants | 46 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants | 9 Participants | 9 Participants | 5 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 23 | 0 / 24 | 0 / 12 |
| other Total, other adverse events | 0 / 6 | 0 / 6 | 5 / 6 | 15 / 23 | 17 / 24 | 2 / 12 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 23 | 0 / 24 | 0 / 12 |
Outcome results
Primary
Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye
IOP is a measurement of the pressure inside the eye and was measured using Goldmann applanation tonometry. Study participants used the study medications in both eyes for 14 days. One eye was designated as the Study Eye at baseline: eyes that met inclusion and exclusion criteria. If both eyes were eligible, the study eye was the eye with higher IOP at Baseline at Hour 0. If both eyes had the same IOP at this timepoint, the right eye was designated as the study eye. IOP was measured at Baseline and Day 14 at Hours 0, 2, 4 and 8. The primary endpoint was the mean change from baseline IOP at Day 14, Hour 2, the timepoint of the peak effect of timolol.
Time frame: Baseline, Day 14
Population: Modified Intent-to-Treat Population (mITT) with Last Observation Carried Forward: the mITT population consisted of all randomized and treated subjects who provided IOP data at baseline and had at least one post-baseline IOP assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 2: WB007 0.15% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Baseline Hour 0 | 26.3 millimeters of mercury (mm Hg) | Standard Deviation 2.13 |
| Part 2: WB007 0.15% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Baseline Hour 2 | 24.8 millimeters of mercury (mm Hg) | Standard Deviation 2.59 |
| Part 2: WB007 0.15% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Baseline Hour 4 | 25.0 millimeters of mercury (mm Hg) | Standard Deviation 2.66 |
| Part 2: WB007 0.15% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Baseline Hour 8 | 24.3 millimeters of mercury (mm Hg) | Standard Deviation 2.6 |
| Part 2: WB007 0.15% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Day 14 Hour 0 | -2.6 millimeters of mercury (mm Hg) | Standard Deviation 2.56 |
| Part 2: WB007 0.15% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Day 14 Hour 2 | -4.9 millimeters of mercury (mm Hg) | Standard Deviation 1.85 |
| Part 2: WB007 0.15% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Day 14 Hour 4 | -4.3 millimeters of mercury (mm Hg) | Standard Deviation 1.98 |
| Part 2: WB007 0.15% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Day 14 Hour 8 | -1.8 millimeters of mercury (mm Hg) | Standard Deviation 2.08 |
| Part 2: WB007 0.4% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Baseline Hour 4 | 24.8 millimeters of mercury (mm Hg) | Standard Deviation 2.27 |
| Part 2: WB007 0.4% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Day 14 Hour 4 | -3.6 millimeters of mercury (mm Hg) | Standard Deviation 2.94 |
| Part 2: WB007 0.4% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Baseline Hour 8 | 23.9 millimeters of mercury (mm Hg) | Standard Deviation 2 |
| Part 2: WB007 0.4% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Day 14 Hour 0 | -3.3 millimeters of mercury (mm Hg) | Standard Deviation 2.55 |
| Part 2: WB007 0.4% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Day 14 Hour 2 | -5.1 millimeters of mercury (mm Hg) | Standard Deviation 2.51 |
| Part 2: WB007 0.4% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Baseline Hour 0 | 26.1 millimeters of mercury (mm Hg) | Standard Deviation 2.17 |
| Part 2: WB007 0.4% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Baseline Hour 2 | 24.8 millimeters of mercury (mm Hg) | Standard Deviation 2.16 |
| Part 2: WB007 0.4% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Day 14 Hour 8 | -1.8 millimeters of mercury (mm Hg) | Standard Deviation 2.88 |
| Part 2: Timolol 0.5% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Baseline Hour 4 | 25.8 millimeters of mercury (mm Hg) | Standard Deviation 4.5 |
| Part 2: Timolol 0.5% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Baseline Hour 2 | 26.7 millimeters of mercury (mm Hg) | Standard Deviation 4.29 |
| Part 2: Timolol 0.5% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Baseline Hour 0 | 27.1 millimeters of mercury (mm Hg) | Standard Deviation 3.53 |
| Part 2: Timolol 0.5% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Baseline Hour 8 | 26.1 millimeters of mercury (mm Hg) | Standard Deviation 4.85 |
| Part 2: Timolol 0.5% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Day 14 Hour 4 | -4.0 millimeters of mercury (mm Hg) | Standard Deviation 3.41 |
| Part 2: Timolol 0.5% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Day 14 Hour 2 | -6.0 millimeters of mercury (mm Hg) | Standard Deviation 3.05 |
| Part 2: Timolol 0.5% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Day 14 Hour 0 | -5.3 millimeters of mercury (mm Hg) | Standard Deviation 2.93 |
| Part 2: Timolol 0.5% | Part 2: Mean Change From Baseline in Intraocular Pressure (IOP) at Day 14 - Study Eye | Day 14 Hour 8 | -5.5 millimeters of mercury (mm Hg) | Standard Deviation 3.33 |
Comparison: A within-group comparison was performed between Baseline, Hour 2 and Day 14, Hour 2, the timepoint for the peak effect of Timolol 0.5%.p-value: <0.00195% CI: [-5.73, -4.14]t-test, 2 sided
Comparison: A within-group comparison was performed between Baseline, Hour 2 and Day 14, Hour 2, the timepoint for the peak effect of Timolol 0.5%.p-value: <0.00195% CI: [-6.14, -4.02]t-test, 2 sided
Comparison: A within-group comparison was performed between Baseline, Hour 2 and Day 14, Hour 2, the timepoint for the peak effect of Timolol 0.5%.p-value: <0.00195% CI: [-7.93, -4.07]t-test, 2 sided
Comparison: The mean IOP change from Baseline, Hour 2 to Day 14, Hour 2 (the timepoint for the peak effect of Timolol 0.5%) was compared between WB007 0.15% and Timolol 0.5%.p-value: 0.82895% CI: [-1.16, 1.43]ANCOVA
Comparison: The mean IOP change from Baseline, Hour 2 to Day 14, Hour 2 (the timepoint for the peak effect of Timolol 0.5%) was compared between WB007 0.4% and Timolol 0.5%.p-value: 0.5295% CI: [-1.73, 0.89]ANCOVA
Secondary
Part 2: Mean IOP at Day 14 - Study Eye
IOP is a measurement of the pressure inside the eye and was measured using Goldmann applanation tonometry. Study participants used the study medications in both eyes for 14 days. One eye was designated as the Study Eye at baseline: eyes that met inclusion and exclusion criteria. If both eyes were eligible, the study eye was the eye with higher IOP at Baseline at Hour 0. If both eyes had the same IOP at this timepoint, the right eye was designated as the study eye. IOP was measured at Baseline and Day 14 at Hours 0, 2, 4 and 8. The primary timepoint was at Day 14, Hour 2, the timepoint of the peak effect of timolol.
Time frame: Baseline, Day 14
Population: Modified Intent-to-Treat Population (mITT) with Last Observation Carried Forward: the mITT population consisted of all randomized and treated subjects who provided IOP data at baseline and had at least one post-baseline IOP assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 2: WB007 0.15% | Part 2: Mean IOP at Day 14 - Study Eye | Baseline, Hour 0 | 26.3 millimeters of mercury (mm Hg) | Standard Deviation 2.13 |
| Part 2: WB007 0.15% | Part 2: Mean IOP at Day 14 - Study Eye | Day 14, Hour 8 | 22.6 millimeters of mercury (mm Hg) | Standard Deviation 3.74 |
| Part 2: WB007 0.15% | Part 2: Mean IOP at Day 14 - Study Eye | Baseline, Hour 4 | 25.0 millimeters of mercury (mm Hg) | Standard Deviation 2.66 |
| Part 2: WB007 0.15% | Part 2: Mean IOP at Day 14 - Study Eye | Day 14, Hour 0 | 23.7 millimeters of mercury (mm Hg) | Standard Deviation 3.83 |
| Part 2: WB007 0.15% | Part 2: Mean IOP at Day 14 - Study Eye | Baseline, Hour 8 | 24.3 millimeters of mercury (mm Hg) | Standard Deviation 2.6 |
| Part 2: WB007 0.15% | Part 2: Mean IOP at Day 14 - Study Eye | Day 14, Hour 4 | 20.7 millimeters of mercury (mm Hg) | Standard Deviation 3.1 |
| Part 2: WB007 0.15% | Part 2: Mean IOP at Day 14 - Study Eye | Baseline, Hour 2 | 24.8 millimeters of mercury (mm Hg) | Standard Deviation 2.59 |
| Part 2: WB007 0.15% | Part 2: Mean IOP at Day 14 - Study Eye | Day 14, Hour 2 | 19.9 millimeters of mercury (mm Hg) | Standard Deviation 2.47 |
| Part 2: WB007 0.4% | Part 2: Mean IOP at Day 14 - Study Eye | Day 14, Hour 4 | 21.2 millimeters of mercury (mm Hg) | Standard Deviation 2.89 |
| Part 2: WB007 0.4% | Part 2: Mean IOP at Day 14 - Study Eye | Day 14, Hour 2 | 19.7 millimeters of mercury (mm Hg) | Standard Deviation 1.83 |
| Part 2: WB007 0.4% | Part 2: Mean IOP at Day 14 - Study Eye | Baseline, Hour 0 | 26.1 millimeters of mercury (mm Hg) | Standard Deviation 2.17 |
| Part 2: WB007 0.4% | Part 2: Mean IOP at Day 14 - Study Eye | Day 14, Hour 8 | 22.1 millimeters of mercury (mm Hg) | Standard Deviation 2.52 |
| Part 2: WB007 0.4% | Part 2: Mean IOP at Day 14 - Study Eye | Baseline, Hour 2 | 24.8 millimeters of mercury (mm Hg) | Standard Deviation 2.16 |
| Part 2: WB007 0.4% | Part 2: Mean IOP at Day 14 - Study Eye | Baseline, Hour 4 | 24.8 millimeters of mercury (mm Hg) | Standard Deviation 2.27 |
| Part 2: WB007 0.4% | Part 2: Mean IOP at Day 14 - Study Eye | Baseline, Hour 8 | 23.9 millimeters of mercury (mm Hg) | Standard Deviation 2 |
| Part 2: WB007 0.4% | Part 2: Mean IOP at Day 14 - Study Eye | Day 14, Hour 0 | 22.9 millimeters of mercury (mm Hg) | Standard Deviation 2.42 |
| Part 2: Timolol 0.5% | Part 2: Mean IOP at Day 14 - Study Eye | Day 14, Hour 8 | 20.6 millimeters of mercury (mm Hg) | Standard Deviation 3.66 |
| Part 2: Timolol 0.5% | Part 2: Mean IOP at Day 14 - Study Eye | Baseline, Hour 8 | 26.1 millimeters of mercury (mm Hg) | Standard Deviation 4.85 |
| Part 2: Timolol 0.5% | Part 2: Mean IOP at Day 14 - Study Eye | Baseline, Hour 2 | 26.7 millimeters of mercury (mm Hg) | Standard Deviation 4.29 |
| Part 2: Timolol 0.5% | Part 2: Mean IOP at Day 14 - Study Eye | Baseline, Hour 4 | 25.8 millimeters of mercury (mm Hg) | Standard Deviation 4.5 |
| Part 2: Timolol 0.5% | Part 2: Mean IOP at Day 14 - Study Eye | Day 14, Hour 0 | 21.8 millimeters of mercury (mm Hg) | Standard Deviation 1.64 |
| Part 2: Timolol 0.5% | Part 2: Mean IOP at Day 14 - Study Eye | Day 14, Hour 2 | 20.7 millimeters of mercury (mm Hg) | Standard Deviation 2.18 |
| Part 2: Timolol 0.5% | Part 2: Mean IOP at Day 14 - Study Eye | Day 14, Hour 4 | 21.8 millimeters of mercury (mm Hg) | Standard Deviation 3.22 |
| Part 2: Timolol 0.5% | Part 2: Mean IOP at Day 14 - Study Eye | Baseline, Hour 0 | 27.1 millimeters of mercury (mm Hg) | Standard Deviation 3.53 |
Comparison: The mean IOP for WB007 0.15% was compared to Timolol 0.5% at Day 14, Hour 2, the timepoint for the peak effect of Timolol 0.5% and the primary efficacy timepoint for the study.p-value: 0.82895% CI: [-1.16, 1.43]ANCOVA
Comparison: The mean IOP for WB007 0.4% was compared to Timolol 0.5% at Day 14, Hour 2, the timepoint for the peak effect of Timolol 0.5% and the primary efficacy timepoint for the study.p-value: 0.5295% CI: [-1.73, 0.89]ANCOVA
Comparison: The mean IOP for WB007 0.15% was compared to Timolol 0.5% at Day 14, Hour 2, the timepoint for the peak effect of Timolol 0.5% and the primary efficacy timepoint for the study.p-value: 0.28395% CI: [-2.39, 0.71]ANOVA
Comparison: The mean IOP for WB007 0.4% was compared to Timolol 0.5% at Day 14, Hour 2, the timepoint for the peak effect of Timolol 0.5% and the primary efficacy timepoint for the study.p-value: 0.18995% CI: [-2.56, 0.52]ANOVA