Open-Angle Glaucoma, Ocular Hypertension
Conditions
Keywords
Intraocular pressure
Brief summary
In participants with a diagnosis of open angle glaucoma (OAG) or ocular hypertension (OHT), the primary objective is to demonstrate that the mean IOP reduction after 3 months of treatment with BOL-303259-X once daily (QD) is non-inferior to timolol maleate 0.5% twice daily (BID). The secondary objective is to demonstrate the superiority of BOL-303259-X QD to timolol maleate 0.5% BID. This assessment will be performed if the non-inferiority of BOL-303259-X QD to timolol maleate 0.5% BID is determined. An open label safety phase will be conducted at the end of Visit 6 (3 months) where all participants will receive BOL-303259-X QD for an additional 9 months.
Interventions
DRUGBOL-303259-X
Topical ocular BOL-303259-X will be administered QD in the evening and its vehicle administered QD in the morning for 3 months (visit 6).
DRUGTimolol
Timolol will be administered BID once in the morning and once in the evening for 3 months (Visit 6)
Sponsors
Bausch & Lomb Incorporated
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
* Participants must have a diagnosis of OAG (including pigmentary or pseudoexfoliative) or OHT in 1 or both eyes. * Participants must meet the following IOP requirements at Visit 3 * mean/median IOP ≥ 24 mmHg at a minimum of 2 time points in the same eye * IOP ≤ 36 mmHg at all 3 measurement time points in both eyes. * Participants with a best-corrected visual acuity (BCVA), using the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol, of +0.7 logMAR units (Snellen equivalent of approximately 20/100) or better in either eye.
Exclusion criteria
* Participants with known hypersensitivity or contraindications to latanoprost, NO treatment, timolol maleate, other beta-adrenergic receptor antagonists or any of the ingredients in the study drugs. * Participants with a central corneal thickness greater than 600 μm in either eye. * Participants with advanced glaucoma and participants with a cup/disc ratio greater than 0.8 or a history of split fixation, or a field loss threatening fixation in either eye. * Participants who do not have an intact posterior capsule in either eye . * Participants with aphakia in either eye. * Participants with previous or active corneal disease in either eye. * Participants with current or a history of severe dry eye in either eye. * Participants with current or a history of optic disc hemorrhage in either eye. * Participants with current or a history of central/branch retinal vein or artery occlusion in either eye. * Participants with current or a history of macular edema in either eye. * Participants with very narrow angles (3 quadrants with less than Grade 2 according to Shaffer's anterior chamber angle grading system) and Participants with angle closure,congenital, and secondary glaucoma, and participants with history of angle closure in either eye. * Participants with a diagnosis of a clinically significant or progressive retinal disease in either eye. * Participants with any intraocular infection or inflammation in either eye within 3 months(90 days) prior to Visit 1 (Screening). * Participants with a history of ocular laser surgery in either eye within the 3 months(90 days) prior to Visit 1 (Screening). * Participants with a history of incisional ocular surgery or severe trauma in either eye within 3 months (90 days) prior to Visit 1 (Screening).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean IOP | 8 AM, 12 PM, and 4 PM at Visit 4(Week 2), Visit 5 (Week 6), and Visit 6 (Month 3) | Mean intraocular pressure (IOP) in study eye measured at the specified time points: 8 AM, 12 PM, and 4 PM at Visit 4(Week 2), Visit 5 (Week 6), and Visit 6 (Month 3). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate - IOP ≤ 18 mm Hg | 8 AM, 12 PM, and 4 PM at Visit 4(Week 2), Visit 5 (Week 6), and Visit 6 (Month 3). | Percentage of participants with IOP ≤ 18 mm Hg consistently at all 9 time points in the first 3 months |
| Response Rate - IOP Reduction ≥ 25% | 8 AM, 12 PM, and 4 PM at Visit 4(Week 2), Visit 5 (Week 6), and Visit 6 (Month 3). | Percentage of participants with IOP reduction ≥ 25% consistently at all 9 time points in the first 3 months |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Ocular and Systemic Adverse Events | 12 months | Following assessments through Visit 6 (Month 3), all participants, irrespective of previous randomization, converted to a single open label safety arm receiving BOL-303259-X QD in the evening. Adverse events were recorded throughout the comparative efficacy phase and open label extension phase. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BOL-303259-X BOL-303259-X ophthalmic solution QD (PM) and vehicle QD (AM) administered for 3 months (Visit 6) into the study eye during the efficacy phase, and for an additional 9 months from Visit 6 through Visit 9 (1 year) during the open label safety extension phase | 284 |
| Timolol Timolol maleate ophthalmic solution, 0.5%, administered BID for 3 months (Visit 6) into study eye. thereafter these subjects were switched to receive topical ocular BOL-303259-X QD in the evening for an additional 9 months from Visit 6 through Visit 9 (1 year) | 133 |
| Total | 417 |
Baseline characteristics
| Characteristic | Timolol | Total | BOL-303259-X |
|---|---|---|---|
| Age, Continuous | 63.1 years STANDARD_DEVIATION 11.23 | 64.2 years STANDARD_DEVIATION 10.63 | 64.7 years STANDARD_DEVIATION 10.32 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 43 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 120 Participants | 374 Participants | 254 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 24 Participants | 88 Participants | 64 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 108 Participants | 325 Participants | 217 Participants |
| Sex: Female, Male Female | 77 Participants | 243 Participants | 166 Participants |
| Sex: Female, Male Male | 56 Participants | 174 Participants | 118 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 11 / 283 | 3 / 135 | 5 / 385 |
| serious Total, serious adverse events | 3 / 283 | 2 / 135 | 8 / 385 |
Outcome results
Primary
Mean IOP
Mean intraocular pressure (IOP) in study eye measured at the specified time points: 8 AM, 12 PM, and 4 PM at Visit 4(Week 2), Visit 5 (Week 6), and Visit 6 (Month 3).
Time frame: 8 AM, 12 PM, and 4 PM at Visit 4(Week 2), Visit 5 (Week 6), and Visit 6 (Month 3)
Population: Intent-to-treat population with LOCF
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| BOL-303259-X | Mean IOP | 12 pm week 2 | 18.00 mm Hg | Standard Deviation 3.376 |
| BOL-303259-X | Mean IOP | 12 pm week 6 | 17.84 mm Hg | Standard Deviation 3.305 |
| BOL-303259-X | Mean IOP | 8 am week 2 | 18.61 mm Hg | Standard Deviation 3.544 |
| BOL-303259-X | Mean IOP | 4 pm week 6 | 17.82 mm Hg | Standard Deviation 3.513 |
| BOL-303259-X | Mean IOP | 4 pm week 2 | 18.09 mm Hg | Standard Deviation 3.293 |
| BOL-303259-X | Mean IOP | 12 pm Month 3 | 17.88 mm Hg | Standard Deviation 3.409 |
| BOL-303259-X | Mean IOP | 8 am Month 3 | 18.71 mm Hg | Standard Deviation 3.382 |
| BOL-303259-X | Mean IOP | 4 pm Month 3 | 17.83 mm Hg | Standard Deviation 3.521 |
| BOL-303259-X | Mean IOP | 8 am week 6 | 18.59 mm Hg | Standard Deviation 3.525 |
| Timolol | Mean IOP | 4 pm Month 3 | 19.15 mm Hg | Standard Deviation 3.643 |
| Timolol | Mean IOP | 8 am week 2 | 19.84 mm Hg | Standard Deviation 3.651 |
| Timolol | Mean IOP | 12 pm week 2 | 19.37 mm Hg | Standard Deviation 3.696 |
| Timolol | Mean IOP | 4 pm week 2 | 19.20 mm Hg | Standard Deviation 3.359 |
| Timolol | Mean IOP | 8 am week 6 | 19.63 mm Hg | Standard Deviation 3.243 |
| Timolol | Mean IOP | 12 pm week 6 | 19.09 mm Hg | Standard Deviation 3.23 |
| Timolol | Mean IOP | 8 am Month 3 | 19.73 mm Hg | Standard Deviation 2.23 |
| Timolol | Mean IOP | 12 pm Month 3 | 19.15 mm Hg | Standard Deviation 3.311 |
| Timolol | Mean IOP | 4 pm week 6 | 19.09 mm Hg | Standard Deviation 3.492 |
p-value: <0.01ANCOVA
Secondary
Response Rate - IOP ≤ 18 mm Hg
Percentage of participants with IOP ≤ 18 mm Hg consistently at all 9 time points in the first 3 months
Time frame: 8 AM, 12 PM, and 4 PM at Visit 4(Week 2), Visit 5 (Week 6), and Visit 6 (Month 3).
Population: Intent-to-treat population with LOCF
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BOL-303259-X | Response Rate - IOP ≤ 18 mm Hg | 65 Participants |
| Timolol | Response Rate - IOP ≤ 18 mm Hg | 15 Participants |
p-value: 0.005Chi-squared
Secondary
Response Rate - IOP Reduction ≥ 25%
Percentage of participants with IOP reduction ≥ 25% consistently at all 9 time points in the first 3 months
Time frame: 8 AM, 12 PM, and 4 PM at Visit 4(Week 2), Visit 5 (Week 6), and Visit 6 (Month 3).
Population: Intent-to-treat with LOCF
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BOL-303259-X | Response Rate - IOP Reduction ≥ 25% | 99 Participants |
| Timolol | Response Rate - IOP Reduction ≥ 25% | 26 Participants |
p-value: 0.001Chi-squared
Other Pre-specified
Number of Participants With Ocular and Systemic Adverse Events
Following assessments through Visit 6 (Month 3), all participants, irrespective of previous randomization, converted to a single open label safety arm receiving BOL-303259-X QD in the evening. Adverse events were recorded throughout the comparative efficacy phase and open label extension phase.
Time frame: 12 months
Population: Safety population (analyzed as treated). Of the 420 subjects randomized, 418 instilled at least one dose of study medication and were included in the safety population; one subject randomized to BOL-303259-X received timolol in the efficacy phase and was therefore analyzed as part of the timolol treatment group.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BOL-303259-X | Number of Participants With Ocular and Systemic Adverse Events | >/= 1 nonocular AE | 36 Participants |
| BOL-303259-X | Number of Participants With Ocular and Systemic Adverse Events | >/= 1 ocular (Study eye) AE | 38 Participants |
| Timolol | Number of Participants With Ocular and Systemic Adverse Events | >/= 1 nonocular AE | 19 Participants |
| Timolol | Number of Participants With Ocular and Systemic Adverse Events | >/= 1 ocular (Study eye) AE | 16 Participants |
| BOL-303259-X Safety Extension Phase | Number of Participants With Ocular and Systemic Adverse Events | >/= 1 nonocular AE | 62 Participants |
| BOL-303259-X Safety Extension Phase | Number of Participants With Ocular and Systemic Adverse Events | >/= 1 ocular (Study eye) AE | 46 Participants |