Ocular Hypertension, Open Angle Glaucoma
Conditions
Brief summary
This clinical investigation is being performed to compare the effect of BOL-303259-X dosed once daily (QD) with timolol maleate 0.5% dosed twice daily (BID) in reducing intraocular pressure (IOP) measured over a 24-hour period in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT).
Interventions
DRUGBOL-303259-X
Topical ophthalmic solution
DRUGTimolol maleate
Topical ophthalmic solution
Sponsors
Bausch & Lomb Incorporated
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must have a diagnosis of OAG or OHT in 1 or both eyes. * Subjects who are treatment-naïve must meet the following IOP requirements at Visit 1 (Screening), and pretreated subjects must meet the following IOP requirements at Visit 2 (Washout): Intraocular pressure ≥ 22 mmHg in at least 1 eye and ≤ 36 mmHg in both eyes.
Exclusion criteria
* Subjects who have been exposed to BOL-303259-X within 3 months prior to Visit 1 (Screening). * Subjects with a history or presence of chronic generalized systemic disease that the Investigator feels might increase the risk to the subject or confound the results of the study. * Subjects with an irregular daily sleep schedule. * Subjects who are unable to wear sleep monitoring device for 7 days prior to laboratory study. * Subjects with an anticipated need to initiate or modify medication (systemic or topical) that is known to affect IOP. * Subjects for whom concomitant use of medications may interact with the safety or efficacy of a nitric oxide. * Subjects with known hypersensitivity or contraindications to latanoprost or any of the ingredients in the study drugs. * Subjects who are expected to require treatment with ocular or systemic corticosteroids. * Subjects who are in need of any other topical or systemic treatment of OAG or OHT. * Subjects who are unable to discontinue contact lens use during and for 24 hours before the laboratory study. * Subjects with a central corneal thickness greater than 600 μm in either eye. * Subjects with any condition that prevents reliable applanationtonometry in either eye. * Subjects with advanced glaucoma and subjects with a cup/disc ratio greater than 0.8 or a history of split fixation, or a field loss threatening fixation in either eye. * Subjects with previous or active corneal disease. * Subjects with a history of severe dry eye. * Subjects with active optic disc hemorrhage. * Subjects with a history of central/branch retinal vein or artery occlusion. * Subjects with a history of macular edema. * Subjects with very narrow angles and subjects with angle closure, congenital, and secondary glaucoma, and subjects with history of angle closure in either eye. * Subjects with a diagnosis of a clinically significant or progressive retinal disease in either eye. * Subjects with any intraocular infection or inflammation within 3 months prior to Visit 1 (Screening). * Subjects with a history of ocular laser surgery within the 3 months prior to Visit 1 (Screening). * Subjects with a history of incisional ocular surgery or severe trauma within 3 months prior to Visit 1 (Screening).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24 Hour IOP | after 4 weeks of treatment | Supine intraocular pressure (IOP) measured in the study eye following 4 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 24-hour Ocular Perfusion Pressure | after 4 weeks of treatment | Sitting Ocular Perfusion Pressure = 95/140 x mean arterial blood pressure - IOP; Supine Ocular Perfusion Pressure = 115/130 x mean arterial blood pressure - IOP; the nocturnal time frame encompassed measures taken at 10pm, 12am, 2am and 4 am; whereas the diurnal time frame encompassed measures taken at 6am, 8am, 10am, 12pm, 2pm, 4pm, 6pm, and 8pm. |
| IOP Area Under the Curve Over 24 Hours | after 4 weeks of treatment | The Area Under the Curve(AUC) is the weighted average of IOP over all 24-hour IOP assessment times (2pm, 4pm, 6pm, 8pm, 10pm, 12am, 2am, 4am, 6am, 8am, 10am, 12pm). The AUC was calculated using the trapezoidal rule. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Participants who were randomized to receive either latanoprostene ophthalmic solution 0.024% or timolol maleate 0.5% | 21 |
| Total | 21 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Age, Continuous | 61.0 years STANDARD_DEVIATION 11.13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 7 Participants |
| Treatment-Naive | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 4 / 23 | 1 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 |
Outcome results
Primary
24 Hour IOP
Supine intraocular pressure (IOP) measured in the study eye following 4 weeks of treatment
Time frame: after 4 weeks of treatment
Population: Intent to Treat (ITT) Population:All randomized subjects who received at least one dose of study drug, had a baseline and at least one postbaseline intraocular assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Timolol Maleate | 24 Hour IOP | 23.55 mm Hg | Standard Deviation 2.46 |
| BOL-303259-X | 24 Hour IOP | 21.77 mm Hg | Standard Deviation 2.37 |
p-value: <0.00195% CI: [-2.38, -1.166]ANCOVA
Secondary
24-hour Ocular Perfusion Pressure
Sitting Ocular Perfusion Pressure = 95/140 x mean arterial blood pressure - IOP; Supine Ocular Perfusion Pressure = 115/130 x mean arterial blood pressure - IOP; the nocturnal time frame encompassed measures taken at 10pm, 12am, 2am and 4 am; whereas the diurnal time frame encompassed measures taken at 6am, 8am, 10am, 12pm, 2pm, 4pm, 6pm, and 8pm.
Time frame: after 4 weeks of treatment
Population: Intent to Treat (ITT): All randomized subjects who received at least one dose of study drug, had a baseline, and at least one post baseline intraocular assessment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Timolol Maleate | 24-hour Ocular Perfusion Pressure | OPP (nocturnal) | 48.4 mm Hg | Standard Deviation 9.4 |
| Timolol Maleate | 24-hour Ocular Perfusion Pressure | OPP (Diurnal supine) | 54.8 mm Hg | Standard Deviation 7.5 |
| Timolol Maleate | 24-hour Ocular Perfusion Pressure | OPP (Diurnal sitting) | 43.2 mm Hg | Standard Deviation 5.7 |
| BOL-303259-X | 24-hour Ocular Perfusion Pressure | OPP (nocturnal) | 52.5 mm Hg | Standard Deviation 9.5 |
| BOL-303259-X | 24-hour Ocular Perfusion Pressure | OPP (Diurnal supine) | 55.9 mm Hg | Standard Deviation 7.8 |
| BOL-303259-X | 24-hour Ocular Perfusion Pressure | OPP (Diurnal sitting) | 45.2 mm Hg | Standard Deviation 6.8 |
Comparison: Statistical analysis of nocturnal (supine) OPP was performed among baseline, the BOL-303259-X treatment and timolol treatment using ANOVA. the criteria for statistical significance was P\<0.05. Post hoc Bonferroni T-tests were then utilized to compare BOL and timolol groups.p-value: <0.05ANOVA
Secondary
IOP Area Under the Curve Over 24 Hours
The Area Under the Curve(AUC) is the weighted average of IOP over all 24-hour IOP assessment times (2pm, 4pm, 6pm, 8pm, 10pm, 12am, 2am, 4am, 6am, 8am, 10am, 12pm). The AUC was calculated using the trapezoidal rule.
Time frame: after 4 weeks of treatment
Population: ITT population
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Timolol Maleate | IOP Area Under the Curve Over 24 Hours | 23.54 mm Hg | Standard Deviation 2.44 |
| BOL-303259-X | IOP Area Under the Curve Over 24 Hours | 21.77 mm Hg | Standard Deviation 2.29 |
p-value: 0.00495% CI: [-2.915, -0.625]ANOVA